ets exposure, lung cancer - Legacy Tobacco Documents Library
ets exposure, lung cancer - Legacy Tobacco Documents Library
ets exposure, lung cancer - Legacy Tobacco Documents Library
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28 Mar.95 RWA/BRA C :\DATA\ETS\REGISTER .DOC<br />
ETS EXPOSURE, LUNG CANCER<br />
TABLE OF CONTENTS<br />
STUDY REGISTER NO .<br />
General Comments 1<br />
Brownson et al ., 1982 2<br />
Fontham et al ., 1991 and 1994 3<br />
Garfinkel e a( ., 1985 4<br />
Kabat and Wynder, 1984 5<br />
Kabat, 1990 6<br />
Kalandidi et al ., 1990 7<br />
Koo et al ., 1984 and 1987 8<br />
Lee et al ., 1986 9<br />
Shimizu et al . 1988 10<br />
Stockwell et al ., 1992 11<br />
Wu et al ., 1985 12<br />
Wu-Williams et al ., 1990 13<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
PROGRAM & ABSTRACTS<br />
j . 4 . -t-,~ " ,<br />
.t, rr .- . 95<br />
~ ~ ~~ ~~ ~~ 71 71 ~l ~b~- b ~<br />
TIIE SCIENTIFIC PRESENTATION ON EVVIRONMENTAL TOBACCO SHORE AND INDOOR AIR QUALITY<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
1993 . 11, 23 (~ )<br />
q x~ ~ )<br />
SEOUL PALACE HOTEL (KUNGJL~ HALL)<br />
~l xa~}~ q~~ 11 ~ 0 0 3°0~<br />
THE SMOKING FAMILY CLUB
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
2U290a1379
PROGRAM & ABSTRACTS<br />
t~ -176, 11--j 11 b1-1- 714 -Ai A i~~- 71 oi l ~- t-~ - a4 ~ 4 b,d A<br />
THE SCIENTIFIC PRESENTATION ON EWIRONMENTAL TOBACCO SMOKE AND INDOOR AIR QUALITY<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
1993 . I1, 23 (~ )<br />
Ajc 2CL ~121 (.t 71<br />
SEOUL PALACE HOTEL (KUNGJtiN HALL)<br />
''x~rd ~ L a~~ L"1 L O 0 O-I<br />
TH<br />
SMOKING FAMILY CLUB
II . Ba A } OU xo<br />
A] : 1993 . 11 . 23(t}) 11 :00<br />
* 10 : 30 - 11 : 00 0 -A - (1~ ~~l )<br />
~ 11 : 00 - 11 : 10 7N<br />
It 1 1 : 10 - 12 : -10<br />
~ 12, : 40 - 1 3 : 10<br />
* 13 : 10 - 1 •1 : 00 .4 . t<br />
IG7 . 7i ~~ A } ol<br />
$O il~ 0,1 I L ~' I o 1 - I 7 O~1 O -1 al ' I C<br />
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O II ~l "o / E 7 ~ -R I- $ ~- r 11 ~i ;;9 °N "I
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
2029051382
Intr.oduction<br />
_ :'t 0 1 933 ?8_8<br />
PHILIP (iIiUF: C M . D .<br />
THE QUESTION OF HEALTH EFFECTS OF<br />
EiJVIRONAIENTAL 1'OBACCO SMOKE EXPOSURE<br />
IN THE NONSMOKER<br />
Philip Witorsc,i, M .D . , FACP, FCCP<br />
Clinical Pro ; essor of Medicine<br />
Adjunct Professor of Physiology<br />
The George Washington University Medical Center<br />
Washington, D .C ., U .S .A .'<br />
The term "ETS" has been used interchangeably !in<br />
both the press and the scienti :ic literature with a variety of ~<br />
other terms, such as "second hand smoke", "involuntary smoking",<br />
and "passive smoking ." ETS is an aged mixture of sidestream<br />
smoke, that produced by direct combustion of a tobacco product<br />
(such as the tip of a burning cigarette) , and exhaled mainstreala<br />
s ;,io}:e (that previously inhaled in the course of active sraoking)~ .<br />
The possibility that ETS may produce adverse health e"fect~<br />
has generated considerable study and controversy . To~_ sn I<br />
Inan a,t h ; f~r~ t fi a?~z-n_F_~ n;31 .<br />
International Aaency for Re_s_<br />
ealt<br />
aaencies i<br />
%_%==W<br />
a nunr p Y Y<br />
L<br />
G<br />
,L- ,- ~y, r,, ~ I as<br />
noted by the Appellate Court in a'highly publicized recent casei<br />
in Au,stralia between the <strong>Tobacco</strong> Institute of Australia Limite<br />
(TIA) and the Australian Federation of Consumer Organisations<br />
Inc . (AFFCO), " the cuestion whether passive smoking causes<br />
disease in non-smokers is a question upon which scientific<br />
research and discussion is continuing,'1<br />
Unfortunately, in many cases political, social and other<br />
agendas appear to have gotten in the way of objective,<br />
disnassionate evaluation of the science in this area . The<br />
purpose of this presentation is to present a critical analysis f<br />
the available scientific data relevant to the question of the<br />
possible health effects of ETS <strong>exposure</strong> in the nonsmoker .<br />
'The author' :, academic affiliation is listed for .tdentificatj~n<br />
pu :poE:os only . The views exnrese.ed here represent the perscr l<br />
opinions of the author and do not necessarily reflect those off flte<br />
universizy, any u'.:her institutions or entities with which he may ~e<br />
affiliated, or any sponsors of his work .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
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T tw t;•! l,-.lP~_ .'~ :j<br />
a
M<br />
bDjDroacbes to the Study of the Health Effects of ETS<br />
Three approaches have been proposed through the years for ~<br />
the study of the issue of health effects of ETS, as follows : Z<br />
conclusions based on the chemical composition of sidestrear„<br />
smoke ; 2) analogy wit .': and extrapolation from studies of tha<br />
health effects of active smoking ; and 3) clinical - experimenta<br />
and epidemiological studies that specifically address the<br />
possible health effects of ETS,<br />
it is virtually impossible and scientifically inappropriatp<br />
to attempt to accurately predict the health effects of ETS by the<br />
first approach, which addresses the potential carcinogenic,<br />
irritant, or physiologic effects of its•individual constituents .<br />
ETS is a complex mixture of chemicals and it is becoming apparelit<br />
from the study of the toxicology of complex mixtures that the<br />
effects of individual chemicals alone are not necessarily<br />
consistent with how they will behave in the presence of other<br />
substances . Furthermore, the concentrations of chemicals in ETP<br />
are greatly diluted as a result of their distribution in a<br />
relatively large but defined space (e .g ., a room), as well as<br />
changed chemically and physically (so-called "aging") .<br />
Analogies between active smoking and ETS <strong>exposure</strong>, the<br />
second approach, are inappropriate, not only because of the<br />
chemical differences between ETS and mainstream smoke, but alsc<br />
because the magnitude of ETS <strong>exposure</strong> is extremely low relativ i<br />
to smoke inhalation during active smoking . Furthermore, the<br />
process of inhalation of ETS is considerably different from thatt<br />
of active smoking . ur ;l&<br />
;6"<br />
A A<br />
Aa , f<br />
',4 `)<br />
0<br />
ith I<br />
T6--µ' ~ „ the only valid and concrete<br />
information pertaining to the issue of health effects of Ei~S hab<br />
been obtained from experimental and epidemiological studies . i<br />
~<br />
~<br />
ExperimentaL<br />
studies in hu-7-lans usually involve short-term <strong>exposure</strong> of subjec-s<br />
to predetermined concentrations of ETS for a defined perioa of<br />
time, with recording of physiological and clinical responses t6<br />
such <strong>exposure</strong>s . These'experimental studies,* which will be<br />
discussed below, relate more to the acute effects of EI'S rathet~<br />
than to the .r,hronic effects of such <strong>exposure</strong> . The only data 4<br />
available: on the cY,ronic health effacts of ETS <strong>exposure</strong> in tI e j<br />
nonamoke•r hava been obtained from epid?miologic studies . I<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
2<br />
--2 l)
Epidemioloaie Methodoloay,<br />
Fpi.demiology involves the study of the occurrence rate off<br />
disease and its association wit2-h specific <strong>exposure</strong>s and other<br />
factors in popul .ation groups .<br />
In the process of epidemiologic investigation, the<br />
researcher classifies subjects in a study according to whether ~r<br />
not they have a condition or disease of interest (for exaraple, ~<br />
<strong>lung</strong> <strong>cancer</strong>) and according to whether or not they have been<br />
exposed to a factor of interest (for example, ETS) . The result!G<br />
of this classification are then expressed as an "odds ratio" o~<br />
"relative risk", which reflects the occurrence rate of the<br />
disease in the exposed individual relative to the occurrence raf e<br />
of the disease in the nonexposed individual,<br />
casesS fl<br />
t:he<br />
or<br />
The results of all biologic studies, be they experimental ~r<br />
epidemiologic, are subject to considerable uncertainty, since<br />
variability from subject to subject is an inherent characteristuc<br />
of biologic processes . Furthermore, in epidemiologic studies, as<br />
a practical matter, only a relatively small sample of a nuch ~<br />
larger population can he studied directly . Thus, the<br />
investigator must attempt to determine whether an observation z' ;&<br />
a real one (valid and reproducible on re-examination) or one du~a<br />
to chance variation (and not necessarily valid or reproducible)I,<br />
In order to assist the researcher in this determination of<br />
potential reproducibility, reliability and validity of the<br />
observations made, statistical analysis must be employed .<br />
Statistical analyses not only take into consideration the<br />
magnitude of an association but also the biologic variability<br />
a population relative to this association. , !<br />
tl _r_p.~~•~,~ d~<br />
Statistical methods in eoidemiology not only estimate odd3<br />
raLios but also so-called 95%, confidence intervals of the<br />
estir..ate of risk . The 95% confidence interval is an estiL .ate ~ f<br />
the variability and is expressed as a range above and below the ;<br />
"poinz estimate" odds ratio . The wider the interval, t :;a greal-.;-r<br />
the variability . If the lower boundary of the 95,1 confidenc +e<br />
interval exceeds unity (1 .0), the odds ratio is usually regard<br />
as being statistically significant,<br />
v a u a<br />
a~~dds ratio [an~ 9^`= ~-<br />
~ ere statistica?.Lu<br />
ile a stat<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
3<br />
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k<br />
association between a certain <strong>exposure</strong> and a disease state ~<br />
provides the researcher with some assurance that the odds ratio<br />
and the association are meaningful and potentially reproducible~<br />
it is still an estimate with some degree of uncertainty and by r,o<br />
means proves that the <strong>exposure</strong> is the cauve of a par.ticular ~<br />
disease .<br />
An added aspect of uncertainty in epidemiologic studies<br />
relates to the involvement of 'rconfounding variables" and other,<br />
sources of bias that can produce misleading results . Confoundiqg<br />
variables are factors, other than the <strong>exposure</strong> in question, tha~d could influence the occurrence of a disease of interest and must<br />
be adjusted for in the analysis . 3^e%- ;~}l-., U 4,-i k=Jn tha'' 1<br />
jler P i t•d ~~iri ~i nn ?rA rir gk fa .tOr5 'fbr~'anc^~2 . In O Cla~~ft7r<br />
the<br />
of<br />
c<br />
ZTS and Primarv Luna Cancer<br />
To date, 35 published epidemiologic reports have exanined 1the association bet,•ieen ETS <strong>exposure</strong> and primary <strong>lung</strong> <strong>cancer</strong> in ;<br />
the nons,ao!:er [Table 1] . These reports have described studie 's<br />
conducted in Asia (16 reports) ['Table 2], Europe, and the Unitea<br />
States . In most of these studies, nonsmoking women have been the<br />
subjects and spousal smoking has served as the surrogate for or ;<br />
marker of ETS <strong>exposure</strong> . In other words, the risk of <strong>lung</strong> <strong>cancer</strong><br />
due to ETS has been based upon the occurrence rate of the diseabe<br />
in nonsmoking women married to smokers compared to the occurrenCe<br />
rate of the disease in nonsmoking women married to nons
General's Report, the 1986 U .S . National Research Council Reporr,<br />
and the 1992 U .S . Environmental Protection Agency Report) to the<br />
effect that ETS <strong>exposure</strong> is associated with a 15 - 30 % increas~d<br />
risk of <strong>lung</strong> <strong>cancer</strong> are based upon such meta-analyses, the<br />
justification for pooling the data from the various studies intcp<br />
a single statistical analysis and, thus, the validity of sur.h a<br />
conclusion, is a matter of considerable and heated debate .<br />
Another area of co7troversy relates to the surrogate used<br />
for ETS <strong>exposure</strong>, spousal smoking status . Usually, this-index f<br />
<strong>exposure</strong>, which is based upon the response to a questionnaire,<br />
lacks verification by a biologic marker, such as a specific<br />
tobacco constituent in a body fluid (e .g ., urine, plasma, or<br />
saliva levels of nicotine or its metabolite, cotinine) .<br />
Furthermore, spousal smoking has been shown to be an inaccurata<br />
estimate, both qualitatively and quantitatively, of such exposuTe<br />
for the following reasons : 1) it usually fails to differentiat<br />
between spousal smoking in and out of the home ; 2) it does not ~<br />
take into consideration ETS <strong>exposure</strong> from ot'er sources (e .g .,<br />
social or work <strong>exposure</strong>s) ; and 3) it is subject to<br />
misclassification of smoking status of subjects .<br />
With regard to ~ smoking statu~<br />
misclassification, individuals married to smokers have been<br />
demonstrated to have an increased likelihood of being smokers<br />
themselves . This pher.omenon, called "marital concordance" or<br />
"marital aggregation", is recognized to be a potential source o~<br />
inflation of the odds ratio in studies of <strong>lung</strong> <strong>cancer</strong> associateti<br />
with spousal smoking. ' ^
Among the potential confounders that have not been consistently~<br />
considered in the relevant <strong>lung</strong> <strong>cancer</strong> - spousal smoking studieff<br />
are the following : 1) occupational <strong>exposure</strong>s of the subject ; 2)<br />
other <strong>exposure</strong>s of the subject (e .g ., organic solvents) ; 3)<br />
alcohol consumption ; 4) diet and nutrition ; 5) cooking pr.actice ;<br />
6) lifestyle ; 7) socioeconomic status and related issues (e .g .,<br />
quality of medical care, quality of outdoor air around<br />
residence) ; 8) genetic factors ; 9) animal <strong>exposure</strong>s ; and lo)<br />
radiation <strong>exposure</strong> (e,g ., household radon) . Such factors could<br />
have a very significant inipact on the occurrence rate of <strong>lung</strong> ~<br />
<strong>cancer</strong>, acting alone or in combination, and, thus, if not<br />
controlled or adjusted for, can result in an apparent associatic,n<br />
between spousal smoking and <strong>lung</strong> <strong>cancer</strong> when, in fact, there is<br />
no real association .<br />
F9'Sard the RespiratorrL System of Children<br />
i<br />
Epidemiologic studies of the association between ETS %<br />
<strong>exposure</strong> and the incidence of respiratory illness in children<br />
have been examined in two age groups, namely, pre-school childr n<br />
(those under 5 years of age) and older children (5 y-ears of age<br />
or older) . In excess of 40 such'studies have been conducted ini<br />
each of these age groups . Parental (usually maternal) smoking ,<br />
has usually been the surrogate for ETS <strong>exposure</strong> in these studies .<br />
g`Pn s ~ c<br />
~r .<br />
i;ost studies in pre-school children have shown a generally ;<br />
weak but consistent association between maternal .smoking an `d<br />
increased incidence of respiratory symptoms and/or certain acutY<br />
respiratory illnesses in children . t•ihile such an association ~<br />
could be due to the effects of ETS <strong>exposure</strong>, other factor is<br />
related to maternal smoking but distinct from ETS could explain :<br />
this relationship . Among these are in utero effects of active<br />
smoking during pregnancy and the effects of maternal smoking on,<br />
lactation during nursing, both of which have been addressed in i<br />
relatively few of the relevant studies, i= at all . in addition ;<br />
these studies have failed to adequately consider a variety o (f<br />
confounding variables, alone or in co-mbination . P_:uong these ar~<br />
socio2conc,,ic status, gas stove usage, family health history I,<br />
subject's health history, breast feeding, use of day care, ~<br />
nutritional status of the subject, quality of housing, indoor aT1d<br />
outdoor air pollution, and fanily size . I<br />
In contrast to the studies in children under 5 ye,aj~~F, of ag<br />
studies in children 5 years of age or older have failed to<br />
cqnsistently .demonstrate an association between parcnt~l ;$7okinp<br />
and rzspiratory he'i1'tli -effects'in cliildren . Forty-fii~e'studies~<br />
in this age group indic : te that an association between matnrj ;all<br />
sne :,:ing and a specific respiratory symptom (cough, phlegn) or ~<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
6<br />
,
disease (bronchitis, pneumonia, asthma) has been confirmed no !<br />
more than 50% of the time . In these studies the clinical (<br />
endpoints (i .e ., the symptoms and/or diseases addressed) were I<br />
usually obtained from questionnaires completed by the parents and<br />
were conf irmed by phys ician examination or medical reccr :;s less i<br />
than 200 of the time . r v<br />
P tl ] .r °- rr .. pr:.j' .:o ..,y. . 'ja .w & j<br />
~ ~<br />
; jj<br />
~ ,~,~•~dd r<br />
. ~i . . e ° ' As in the studies<br />
sof~ pre-sc o0 .1 chi r2n, these studies in older children<br />
inadequately considered potentially important confounding<br />
variables that could have influenced the outcome of a study,<br />
alone or in combination .<br />
Other Potential Health Effects of ETS<br />
Epidemiologic studies have also attempted to deterraine<br />
whether long-term <strong>exposure</strong> of adults to ETS is associated with<br />
adverse health effects other than <strong>lung</strong> <strong>cancer</strong> . In these studies,<br />
spousal smoking has usually served as the marker for ETS <strong>exposure</strong><br />
(again, without biologic verification) . To date, there are no<br />
consistent data to indicate that•such <strong>exposure</strong>s are asscciated<br />
with increased respiratory illness or impaired pulmonary<br />
function, exacerbation of the condition of individuals wi'th<br />
underlying <strong>lung</strong> disorders (such as emphysema or chronic<br />
obstructive <strong>lung</strong> disease) , increased risk of cardiovascus .ar<br />
disease, or increased risk of <strong>cancer</strong> at sites other than the<br />
luna .<br />
DlQ i<br />
en<br />
'~~.7_C7 " a .<br />
C _<br />
MizMAUM- z<br />
Y 0 har for a def<br />
fi<br />
(1~~ 11~y ~~b0 _minl durin Whi ch tobacco smoke<br />
-<br />
i'!as uJ<br />
~ i~ad<br />
yag iah co h , i r<br />
e<br />
co a ; ~; Acute smoke e ::posurq<br />
evokes responses of e, .~e, nose and throat discomfort, whic : apne~z•<br />
to be due to direct irritative effects of components in t ::bacco~<br />
sro :•ce, rather than an allergic reaction . These acute irritant<br />
responses, arhich are preventable by adequate ventilation (thus<br />
~<br />
reducing levels of <strong>exposure</strong>), do not anpear to produce lc :~g-teri<br />
effeccs or damage organs that are irritated .<br />
~ I<br />
s til C Y 1 ~ ^~}~:~aa~~sri.°3 t~ sn~ rt £~ t. ^ ^~ itc! 1 ~-t ,~~~ttihS~i: ~ 1 O n, ~<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
7<br />
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~
11/91/93 22 :38 1 301 983 38^_S<br />
PHILIP<br />
WITCFECH . ht . D .<br />
WMAN_' e . Furthermore, no valid evidence existsi<br />
that acute ETS <strong>exposure</strong> exacerbates the condition of individual<br />
witri underlying coronary heart disease, and one investigator<br />
making such a claim has been discredited for falsification of<br />
data . The available scientific data also do not suppor-t an<br />
association between ETS <strong>exposure</strong> and harmful effects in the<br />
elderly or the contention that <strong>exposure</strong> of pregnant women to Ei<br />
adversely affects either the mother or the fetus .<br />
To date, approximately seven published studies have examinqd<br />
the acute effects of ETS <strong>exposure</strong> in asthmatic individuals, Nit<br />
conflicting data . While three'studies have reported no adverse<br />
effects, four have reported that acute US <strong>exposure</strong> precipitate<br />
temporary worsening of airflow obstruction on pulmonary functio<br />
testing in some (but not all) asthmatic subjects . These findings<br />
suggest that a subgroup of asthmatics may have an increased<br />
"sensitivity" to ETS . `i,kgi<br />
ncerta i n a 1 t hntirrh t rLata ._i._r.: t~a~co~_~~<br />
Since it is<br />
known that asthma lc attacks can be precipitated by psychologic~l<br />
cues (e .g ., emotional factors or odors) and its uniau.e odor mak s<br />
it difficult to "blind" sub7ects 'to tobacco smoke ex.posure, the<br />
role of psychological and emotional factors in responses of<br />
asthratics remains to be determined .<br />
.<br />
ETS in Context - Indoor Air OualitY I<br />
Although ETS receives a major share of attention among<br />
indcor air pollutants, it is far from the only or even the raostl<br />
important indoor air pollutant . A number of substances pollute~<br />
the indoor air that we breathe . Many of these substances have<br />
important potential adverse health effects, even though these<br />
pollutants are less readily visible or otherwise detectable than<br />
ETS, Some examples include nitrogen dioxide (2102) and other<br />
oxides of nitrogen, sulphur dioxide (S02), ozone (03), carbon<br />
moncxide (CQ), pathogenic and allergenic fungi, bacteria (e .g .,<br />
Leaicn=lla pneumophilia, the cause of Legionnaire's Disease) anc~<br />
viruses, various airborne pollens, dust mites and othe Ir<br />
allergens, volatile organic compounds, and radon gas . Such<br />
substances may pose risks of health impairment that are far<br />
grea ;.er than any conceivably related to ETS, yet they receive<br />
rela :.ively scant atzenticn, in part because their presence is<br />
often undetected without the use of special analytical<br />
techniqu^s, unlike ETS, which is readily visible and has a<br />
distinctiva odor .<br />
Tt is important that ti4: issue of ETS be considered in the! ~<br />
overall cot .text of these other indoor air pollutants and tha ~ G<br />
pot4 ~. :.iz1 h risks that to heal'- they ~ present . It is unLortunata ~ N<br />
that ETS often serves as a"scapegoat" for such other air ~ ~<br />
pollutants, especially since measures directed at elimination of ~<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
~<br />
i<br />
/<br />
~<br />
~<br />
, ~
ETS, such as banning of smoking, have little to no effect on<br />
levels of these other pollutants or their health effects .<br />
Some of these other pollutants have particular relevance t<br />
Asia and especially Korea . A high use of automobiles, energy<br />
conservation measures resulting in "tight", poorly ventilated<br />
buildings, and the utilization of relatively polluting fuels ha e<br />
contributed to making the indoor air in many Asian cities, ~<br />
including a number of Korean cities, highly polluted . Thus, fo<br />
example, studies in 1990 demonstrated that the mean sulphur<br />
dioxide level in Seoul and several other Korean industrial<br />
centers exceeded the applicable environmental standard, i .e ., t e<br />
recommended safe <strong>exposure</strong> level .<br />
_L6Qi&<br />
W" 0<br />
Q"<br />
QII II1-1<br />
~<br />
0<br />
®<br />
q6~o<br />
RM"t&AU s<br />
annrr-+~marcltr Fn~ n==,•xu<br />
0<br />
SIOPPARVale<br />
an<br />
!7- 1, + ; A,<br />
~+ on<br />
~ ® in . More<br />
recently, studies done in Seoul by Kim and associates have<br />
demonstrated higher indoor than outdoor levels of not only carbbn<br />
monoxide, but nitrogen dioxide and formaldehyde as well, largely<br />
attributable to indoor cocking and heating, coupled with poo Ir<br />
ventilation . These studies have also demonstrated that selected<br />
homes in Seoul have significantly elevated levels of radon, a~<br />
naturally occurring radioactive gas that is a potentially<br />
important cause of <strong>lung</strong> <strong>cancer</strong> . I<br />
Conclusions<br />
our analysis of the data reveals that there is little to n~o<br />
good evidence that chronic <strong>exposure</strong> to ETS is a health risk to I<br />
adult individuals . While parental smoking appears to be f<br />
associated with an increased incidence of acute respira-,-)r !'y<br />
illness in pre-school children, no such finding or imoai-r-,ent c ;f<br />
pulmonary function is consistently evident in school-age or oldI ~ar<br />
children . The role of confounding variables and other factors,~<br />
such as in utero effects of smoking during pregnancy, family<br />
health history, and breast feeding, alone or in combination, on<br />
the apparent association between parental smoking and r=_spiratc~ry<br />
illness in young children remains to be elucidated . Althougtl<br />
acute ETS <strong>exposure</strong> may produce eye, nose and throat irrication~in<br />
a concentration-related fashion, there is little to no<br />
that it results in adverse lower respiratory or cardiovascular (<br />
:~ F .~ 'T ;i~<br />
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9
11/01/93 22 :39 1 301 983 38?8 FriILIF WITuFSVH, M .D . F'~~Z_ c li<br />
responses in healthy individuals . While acute ETS <strong>exposure</strong> may<br />
evoke respiratory responses in a subset of asthmatic individuals,<br />
a psychogenic basis for such responses has yet to be ruled out .<br />
As indicated earlier in this presentation, the issue of<br />
health effects of ETS has been examined by several scientific<br />
groups and has lead to reports . Several of these reports hae<br />
stated that ETS <strong>exposure</strong> is a health risk, with particular<br />
emphasis placed on risk of <strong>lung</strong> <strong>cancer</strong> in the nonsmoker and acu~e<br />
respiratory illness and impaired <strong>lung</strong> function and growth in<br />
children . The most recent report that has arrived at such<br />
conclusions is the 1992 U .S . Environmental Protection Agency<br />
(EP.A) Report on the Respiratory Health Effects of Passive<br />
Sraoking .<br />
How can one reconcile our conclusions with those arrived a<br />
by the EPA? To be frank, our analysis is more comprehensive,<br />
more thorough, and more balanced than that appearing in the EPA<br />
report . A review of that report will reveal inconsistencies in<br />
and disparities between the data reviewed and the conclusions<br />
implied or stated in the body of the report, as well as those<br />
implied or conveyed to the press•. It is evident from the ways 'n<br />
which data have been manipulated, explained away, or-interprete by the EPA, and the way in which dissenting opinions have been<br />
addressed, that there is in the EPA Report an unclear separatioll<br />
of objective science from political, social or other agendas, o<br />
preconceived notions. is,<br />
It is important that the issue of ETS be viewed in the<br />
context of indoor air pollution in general . One must keep in<br />
mind the fact that a number of less visible indoor air pollutan,`Ls<br />
present a much more significant health hazard than ETS, even<br />
though the latter attracts considerably more attention and<br />
emotion than the former .<br />
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10
I<br />
11/01/93 22 :38 1 301 983 3829 PHILIP WITORSCH, M .D. PAuE 16<br />
TABLE 2 . STUDIES OF SPOUSAL SMoKIHG AND RISK OF LUPiG CANCER -<br />
ASIAN STUDIES<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
15<br />
7 . .<br />
~<br />
~<br />
~<br />
~<br />
~<br />
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~<br />
W
i]./01/93 22 :38 1 301 983 3928 PHILIP WITORSCH, M .D .<br />
S-=<br />
1 . CHAN 1982<br />
~. T-IRAYAMA 1984<br />
3, LAM 1 985I88<br />
4 . IVL1 1985<br />
5 . A.KIBA 1986<br />
6. GAO 1987<br />
7 . KOO 1987<br />
8, LAM19 7<br />
LIE-LgLIM<br />
10 . INOUE 1988<br />
11 . KATADA 1988<br />
12 . SI-MIIZU 1988<br />
13 . L :[ 1989<br />
14 . SOBUE 1990<br />
15 . 1iE/LIU 199•0/91<br />
HE<br />
0.75<br />
1 .20<br />
1.,52<br />
1 .19<br />
1 .55<br />
2.55<br />
8 .41<br />
1 .10<br />
1 .01<br />
1 .13<br />
0.77<br />
16 . NVU-WI•LLIAIITS 1990 0 .70<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
-4 °i! Fl'l ! .T : :'i~<br />
I0KINt'x AND LU?~I(t~r, ER<br />
95%<br />
0.43, 1 .30<br />
1 .252 .11.<br />
1.02 ; 3,71<br />
0 .60, 2 .50<br />
0 .88, 2 .63<br />
0 .82, 1 .73<br />
0 .90, 2 .67<br />
1,165 2 .35<br />
n 4,29<br />
0 .74, 8 .78<br />
0 .81, 86 .84<br />
0 .65, 1 .85<br />
0 .69, 1 .48<br />
0 .78, 1 .63<br />
0 .30, 1 .96<br />
0 .60, 0 .9-0<br />
PAGE 17
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2025®51395
~ 11/01/93 22 :38 I 301 983 3828 PHILIP WITCRSCH, M .D .<br />
A,SIAIl STTM+QFBPUUS T 9MOK7N+Cx AND LUN- G CANGER<br />
S-1I ER 915% C .r,<br />
1 . CHAN 1982 0 .75 0 .43, 1 .30<br />
Z, H~YAMA, 1984 LJ63 1 .2 2 .11<br />
3 LAM , 1985188 '2 .~..<br />
, .OI<br />
1.0 71<br />
4 ." 1985 1 .20 0 .60, 2 .50<br />
5. AKIBA 1986 1 .52 0 .88, 2 .63<br />
6. GAO 1987 1 .19 0 .82, 1 .73<br />
7 . KOG 1987 1..55 0 .90, 2 .67<br />
$, LA.I4i 19 7 1 .65 1 _2,35<br />
L-Gha . . = 2 .16 0 4,29<br />
10. INGUE 1988 2 .55 0.74, 8 .78<br />
11 . KATADA 1988 8 .41 0 .81, 86 .84<br />
12. SIBIV.IIZU 1988 1 .10 0 .65, 1 .85<br />
13 . LI 1989 1 .01 0 .69, 1 .48<br />
14 . SOBUE 1990 1 .13 0 .78, 1 .63<br />
15 . IiE/LIU 1990/91<br />
0 .77 0.30 , 1 .96<br />
16 . 1V'(J-ZVILLIA.MS 1990 0 .70 0.60, 0 .90<br />
'.L P1'1 ':T'G 4'.= .~11 „h<br />
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PAGE 17<br />
~<br />
G<br />
Ct~:
11/01/93 22 :38 1 301 983 3828 PHILIP WITORSCH, M .D. PAuE 14<br />
TABLE 1 . STUDIES OF SPOUSAL SMOKIPtG AND RISK OF LUNG CANCER °<br />
WORLDWIDE STUDXES<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
~<br />
~<br />
~<br />
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13 ~
11/01/93 22 :38 1 301 983 3828 PHILIP WITORSCH, M .D. PAGE 15<br />
$ I2Y na Pas c .I .<br />
1 . CiARFIKAEL 1981 1 .18 0 .90, 1 .54<br />
2 . CHIIM 1982 0 .75 0,43, 1 .30<br />
3_, TRTCRO?OYJLO9 1983 2 .13 y .19, .4 .Z2<br />
..., . . . .., ~.~<br />
4, CoktRL"A 1983 2 .07 0 .82, 5 .25<br />
5 . AA}3AT 1984 0 .79 0 .25, 2 .45<br />
6 . av7rFLER 1984 0,81 0 .34, 1 .90<br />
7 . I3I7 :.LI8/St11.8; 1984/89 1 .00 0,20, 4 .91<br />
S . MIWIYAMA 1984 1 .63 1 .25<br />
9 . f3AItF I NAEL 1985 1 .31 0 .87, 1 .98<br />
10 .~LAM85/118<br />
;-01<br />
1 .09, 3 .71<br />
11, FiU 1985 1 .20 0 .60, Z :50<br />
12 . ARIBA 1986 1 .52 0 .88, 2 .63<br />
13 . LEE, 1986 1 .00 0 .37, 2,71<br />
14 . 9ROWNSON 1987 1 .52 0 .39, 5 .99<br />
15 . GAO 1987 1 .19 0 .82, .1 .73<br />
16 . HUMHLB 1987 1 .70 0 .60, 4 .30<br />
17 . KOO 1987 1 .55 0 .90, 2 .67<br />
1, ,8,,. LRM 1987 1 .65 1 .16, 2 .35<br />
19 . PFsRSH.AC3E'N 1987 1 .28 0 .76, 2 .15<br />
20 . V.MRELA/JANcRICH 87/90 0 .94 0,76, 1 .17<br />
21 . GENG 1988 2 .16 1 .0 ~ 8 ; 4 .29<br />
72 . INOUE 1988 2 .55<br />
0 .74, 8 .78<br />
23 . K.riTADA 1988 8 .41 0 .81, 86 .84<br />
24 . SHIMIZU 1988 1 .10 0 .65, 1 .85<br />
25 . BUTZ.ER 1988 2 .02 0 .48, 8 .53<br />
26, LI 1989 1 .01 0 .69, 1 .48<br />
27 . 3VEN3SON 1989 1 .26 0 .57, 2 .82<br />
28 . SOBUE 1990 . 1 .13 0 .78, 1 .63<br />
29 . HE/LIU 1990/91 0 .77 0 .30, 1 .96<br />
30 . KA.HAT 1990 0 .90 0 .46, 1 .76 G<br />
31 . KALANDIDI 1990 2 .11 1 .49 , 4 . 08<br />
~<br />
LZ<br />
32 . WU-WILLIADfs 1990 0,70 0 .60, 0 .90<br />
®<br />
~<br />
33 . FONTftAM 1991<br />
M<br />
1 .29 0 .99 , 1 . 69<br />
~<br />
~<br />
34, BROht:15oN 1992 1,00 0 .80, 1 .20 Lo<br />
00<br />
35 . 6TOCF;WELL 1992 1 .60 0 .80, 3 .00<br />
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~
ItLGUt .wT0ttY TOxtO01aGY Ar+D ?IiwlwAcotlxtY 19, 309-316 (1994)<br />
lncanslstency between Workplace and Spousai Studles<br />
of Environmental <strong>Tobacco</strong> Smoke and Lung Cancer'<br />
IvSAUR1CL• E. LL•VO1S" AND MAXWELL W. LAYARDt<br />
'F.nriroemental Nrahh Re .rourcrr, Ttbu,on . Calijornla 94970~ and tLayard .lrsoclates,<br />
Alomrda, Ca!(/ornia 94301<br />
Itccefvcrf January 10. 199!<br />
!n a t'isk astessment ssteased at thc end o( 1992, thc U .S . Environmental Protcetion A ;cncy<br />
(EPA)condudeG that environmental lobacea smokc (ETS) Is a known hunu,n <strong>lung</strong> urdnotea .<br />
The A=ency re.ached that eondusion primarily on the buis of epidcmiolo5ie nudtee of self .rsponed<br />
nevcr•smokin; women, in which the ext>o:ure index was marriagc to a smokcL llowvver, the tuc<br />
of the spousel smoking expoaure surmpate introduces many potcntiat wn(oundinR fseton . Such<br />
confoundins and bias due to denial of activc smokin6 art likely aplanations for weak and in•<br />
consistent rer»nod L•TS-lunz csncer assnciasions . This contention is tupponed by the ruults of<br />
1A wortdvdde studies of lunl pnetr and ETS <strong>exposure</strong> in the workplacc . which in wmbination<br />
indiuted oo risk elcvation . Wnrkplaoe ETS-luaS uncct• studics are not subjoct to the bias and<br />
confounding intsoduaed by the spousal smoking exposutt surrosate. The t:PA Ignored thc workplacc<br />
studies ln its risk auesamont and eatrapolatad the resulu of orwtsaal smoking nudiet to<br />
workplxx and other sourtrt of LT'S exposurt : In its enimate of ETS•ataributable luna< <strong>cancer</strong><br />
deaths in the Unitod Sutes, the EPA asc :ihed over 70% o(thc deaths to nonspousal 1`I'S c~+osurt :,<br />
primarily workplaee ezpocure, Considcrt:d in their entirety, she ETS-<strong>lung</strong> <strong>cancer</strong> enidenioloaic<br />
data do not suppon a uusal infcratea or provide a tcientihc boais for sovernmcnt reSulation of<br />
smotiing in the workptace. o t»r Aols.mK t•rWl, tr.r .<br />
1 . INTRODUCTION<br />
The U .S . Environrucntal Protection Agency (i=.PA) recently issucd a risk assessment<br />
of <strong>lung</strong> eanccr tnonality and environmental tobacco smoke (ETS) <strong>exposure</strong> (U .S .<br />
EPA, 1992) . Tlte EPA report calculated a sumtnnry relative risk oC 1 .19 (909'o confidence<br />
interval, 1 .04-1 .35) from a meta-analysis of results of 11 U .S . studies (9 csse-cantrol<br />
studics and 2 cohort studies) of reportedly never-smoking female subjects. (In a depnrture<br />
from conventional prnetice, the EPA citcd 90% confidcnca intervals for reJativc<br />
risks, on the basis that they corresponded to one•tailed 5% sSgnificance tesu ; a 95%<br />
con5dence interval for the summary rclativc risk is 1 .02-1 .39 .) These studics used<br />
t This work was supported in pan by Thc Tobaero Institutc . The vic-x expressed rrprncnt the pcrsonal<br />
opinioas of the euthon and are not neaessariiy those o(Ths <strong>Tobacco</strong> lnstitutc,<br />
0273-23W/94 T6.00<br />
'~ c- .>fiv, o 1914 !., kninls h.c. uc,<br />
.v ris)"I .rnvud-,:.- u ..r r6 .. ,Ma..,c<br />
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309
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310 I,F.VOIS AND UYAftU<br />
marriagc to a smoker as the b`TS <strong>exposure</strong> indgx . The resulu of each study were<br />
adjusted for smoking status misclassification-currtat or exsmoketa falsely declaring<br />
themsalves to be never-smokcrs-betorc bcing comhined in th : rnetn•analysis . An<br />
adjustment for background <strong>exposure</strong> (<strong>exposure</strong> from soutYxs other than the spouse)<br />
increased the summary rclativc risk to 1 .59 (95% confidencc interval, 1 .02-2.90) . The<br />
relative risk from bttckground ETS exposurc for women married to nonsmokers w-.u<br />
estimsted to be 1 .34 (95% confidencc interval, 1 .01-2 .08) . On the basis of the U .S .<br />
relativc risk estimate of 1 .19 before background adjustment, which was judged to be<br />
statisticafly significant, ond on the basis of the rosults of foreign studies as well as<br />
consideration ofthe biological plausibility of the association, the EPA repon concluded<br />
that there was sufficicnt evidcnce from human studies to ciassify F.'rS as a Group A<br />
(knawn humtin) carcinogen in terms of the EPA Guidelines for Cnrcinogen Risk<br />
Assessment (U .S . EPA, 19$6) .<br />
However, there are problems with the k.PA's risk determination . Its meta-analysis<br />
of U .S . studies omitted two studies which were published before the EPA document<br />
was rcleased ; Brownson et u! . (199' Z) and Stockwcll er ul . (1992) . Using the L'?A's<br />
methods and assumptions, we have calculated a summary relative risk of 1 .07 from<br />
a mera-analysis of 13 U .S . female spousal smoking studies, including these two recent<br />
studies . This relative risk, with 95% conticJence intt :rval of0 .95-1 .21, is not atatistically<br />
significant. Furthermure, iheru is a highly significant (P < 0 .001) inconsistency between<br />
the summary relative risks for six country-specific groups of female spousal smoking<br />
studies considered by the EPA (Table 1) . Thcse relative risks sre all either only wcakly<br />
clevated or, in the atsz of China, below 1,0 . In Section 2 we point out that e likely<br />
explanation for this geographic inconsistency is bias and confounding introduced by<br />
using spousal smoking as an exposurt surrogate . In Section 3 we cxaminc the epidemiologic<br />
data on workplace ETS <strong>exposure</strong>, which were ignored by the EPA but which<br />
overall exhibit no risk elevation . The inconsistency between the spousul and workplace<br />
studies supports the hypothesis that small risk elevations rcponed in some spousal<br />
studies are due to uncontrolled bias and confounding .<br />
2. BIAS ARISING FROM "I'fiE SPOUSAL SMOKING STUDY DES(GN<br />
Grcc= 2 .01 1 .33 3 .04<br />
Honj Kont 1 .49 1 .16 1 .88<br />
lapan 1 .42 1 .15 1 .75<br />
Western Europc 1,16 0,7E 1 .73<br />
United States 1 .07 0 .95 1 .21<br />
China 0 .34 0 .71 1 .00<br />
Wii ST :ZB--`t66i'TZjSLL :-v6biSjb E) A='MIX01 NI S1N01'T1SNO :)<br />
r<br />
:<br />
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ine .>r<br />
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rc c .<br />
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an c!<br />
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13eca<br />
c : nc<br />
in sG<br />
clas`<br />
was .<br />
et a/<br />
The only explanntion offered by the EPA report for the geographic inconsistency a 2 . :<br />
in the spousal smoking studies was that it could he due to d'tffcrences in the intensity is qt<br />
of spousal <strong>exposure</strong> between countrics or to diffrrcnces in the ratio of spousal to nte .<br />
0 .89<br />
et a,<br />
TARLE I<br />
misc<br />
MezA•AN&I.YSCS 6(' SKUtsAL St.tORtNG CrtoYMiotAGiC SttJUtES<br />
clmc<br />
fo rr i<br />
Country Rclntivc risk 95% Cnn6dcnco intcrra7 O coul<br />
N ~ relnt A<br />
tion .<br />
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http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
.' EAlv1RbNMENTAL TU}tACxO ShtOKE AND LUNG CANCF .R 311<br />
nonspousal ETS cxposurc . Nowevcr, these ideas wcrc not supported by any hard<br />
evidence, and no credible dil ;erc:nces in Fl'S <strong>exposure</strong> patterns eould explain the<br />
inconsistency (Layard, ) 992) .<br />
A more likely explanation for the gcographic inconsistency is that the reported<br />
associations are the product of uncontrolled bias and confounding linked with spousal<br />
smoking status and opcntinz in varying degrees in different countries . Spctusal smoking<br />
ic a proxy, or indirect measure of actual ETS <strong>exposure</strong>, and its use introduces a host<br />
of concordant <strong>exposure</strong>s, many of which are potcntial confounders ofreponed spousal<br />
smoking-<strong>lung</strong> catteer associations . Spouses sharc many imponant environmental and<br />
bchavioral risk factors that are likely to confound a reported L i S-<strong>lung</strong> <strong>cancer</strong> associntion<br />
. For example, sntokcrs and thcir spouscs have bccn shown to have dieta lower<br />
in fruiu and vcgctahlcs, and higher in fat and alcohol consumption, than nonsmoking<br />
couples (Friedman er al ., 1983 ; Koo ct al . . 1998 ; Lc Marcltand ct al., 1991 ; Shibata<br />
ur al., 1992 ; Sidney cL al . . 1989 ; Thompson and Warburton, 1993). The magnitude<br />
of dietary confounding is thought to be at (cast as largc as thc reported U .S . spousal<br />
stnoking-<strong>lung</strong> eanccr association (Le Marchand cy al . . 1991 ; Shibata er al., 1992 ;<br />
Sidney et al ., 1989). Other <strong>lung</strong> <strong>cancer</strong> risk factors such as lack of excrcise and low<br />
suciocconomic status (which involves such things as occupation, living condit ;ons,<br />
and quality of hcalth care) atr more common among self-reported never-smoking<br />
spouses ofsmokcrs than among never-smoking spousc .c of nonsmokers. In fact, nearly<br />
every potential confounder that has been identified is likely to inflate a risk estimate<br />
derived from spousal smoking data . None of the L•'1'S-<strong>lung</strong> <strong>cancer</strong> epidcmiologic studies<br />
adequately accounts for the eflccts or most or the known potential confoundcrs .<br />
As wcll aa being cottfoundcd hy numerous <strong>lung</strong> <strong>cancer</strong> risk factors introduced<br />
through spousal concordancc, the spousal smoking study design is generally agreed<br />
to be biased by the misclassification of some current and exsmokers as never•smoken .<br />
13ecause spouses or smokers are more likely to be smokers themselves than spouses<br />
of nonsmokers, denial of smoking is likely to upwardly bias <strong>lung</strong> <strong>cancer</strong> relative risks<br />
in spousal smoking studics . The EP/+ made some adjustment for smoking status misclassification,<br />
but it is doubtful whether the adjustment for the U .S . female studies<br />
was adequatc, in the light of available information on misclassification rates (KJesgcs<br />
et al., 1992 ; Lee, 1992; Pcrez-Stable et al ., 1992 ; %genknccht et al., 1992) . Assuming<br />
a 2 .5% misclassification rate of U .S . female current smokers as never-smokers, which<br />
is quite r„otuistent with avaiiablc data, instead or the F :PA's assumption of a 1 .09%<br />
rate, produces a summary relative risk estimaic of 1 .00 (95% confidence interval,<br />
0 .89-1 .14) from 13 U .S . studics includinz the Rn>wnson c.t a1. (1992) and StocScwcll<br />
e: al. (1992) studics-that is, no risk elevation . Little or no data arc availablc bn<br />
misclattification rates in foreign countries . Tlu EPA's as .aumptions about foreign misclassifiwtion<br />
rates resulted in minuscule or no adjusunent to the relative risks of<br />
foreign studies and could be quite erroneous . Smoking status misclassification, then,<br />
could be another source of tcographic inconsistency in the spousal smoking studies .<br />
Although somc of the spousal smoking-<strong>lung</strong> <strong>cancer</strong> studies reported dose-rrsponse<br />
relationships, the interpretation and importance of the doso-response data arc qurstionablc<br />
. '('hese data lack consistency between studies, and within studies for different<br />
dosc indicrs Most important, many potential confounders of reportcd spousal smoking-<strong>lung</strong><br />
<strong>cancer</strong> tssociations, as well as stnoking ttatus misclassi5retion bias, are correlated<br />
wit0 spousal smoking in a dose-dependcnt fashion (Friedman ct al ., 1983 ; Koo<br />
0
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
312 . LL•VOfS AND t.+.YARt)<br />
er al., 1988 ; Lc Marchand c1 al., 1991), and such corrclations could account for appareuc<br />
dose-responsc trends .<br />
As part of its justiflcation for concluding thrt ETS should be classificd as a Group<br />
A careinogen, the EPA claimed that the proportion of spousal smoking studies reporting<br />
a <strong>lung</strong> <strong>cancer</strong> risk elevation is improbably high and cannot be attributed to chance<br />
alone. However, this argument is meaningless, since it depends on the dubious assumption<br />
that the spousat smokinZ study design is essentially free of uncontrolled<br />
influences, and produces att unbiased estimate of an ETS effcc :t . The opposite assutnption,<br />
that the spousal smoking design is subject to positive bias and confounding,<br />
is more likely to be true, so weak spousal smoking-<strong>lung</strong> <strong>cancer</strong> risk elevations in the<br />
individual studies may well be the result of anifact alotte . Givcn the large number oi'<br />
studies, all using the llawcd spousal smoking study design, a statistical u :sl of association<br />
based on the proportion of positive studies will with high probability detect the influcncc<br />
of bias and confounding inherent in that design ; that is, such a test will likciy be<br />
significant simply due to anifact .<br />
3. WORKPLACE ETS-1 .UNG CANCER STUDIES<br />
Having estimated an ETS-<strong>lung</strong> <strong>cancer</strong> risk from fcmale spousal smoking studies,<br />
the EPA extrapolated that risk to males, to exsmokers, and to workplace and other<br />
nonspousal. ETS <strong>exposure</strong>. A suhstantial majority of thc EPA's estimatcd ETS-attributable<br />
annual U .S . <strong>lung</strong> <strong>cancer</strong> deaths, 2200 of 30G0 total deaths (71 .9So), were ascribed<br />
to nonspousat <strong>exposure</strong> sources, primarily workplace ETS exposurc . Rcmarkably, the<br />
EPA did not use available information front nine U .S, studies of workplace ETS<br />
<strong>exposure</strong> to estimate workplacc ETS-<strong>lung</strong> canccr risk . Instead, the agency axsumcd<br />
that workplace l3TS risk can be axtrapolated from the spousal risk estimate .<br />
However, a comparison bctwcen the workplace BTS-<strong>lung</strong> <strong>cancer</strong> dttta and the<br />
spousal smoking data indicates that the workplacc data are not consistent with even<br />
the weak risk elevations roponed iu some spousal smoking studies, and indeed the<br />
combined workplacc studies exhibit no ETS-<strong>lung</strong> <strong>cancer</strong> association .<br />
To make this comparison, we performed, using the summarization method employed<br />
by the EPA, a meta-analysis of the rt,-sults of 12 studies that have reportcd lutts<br />
caneer relative risks for workplace <strong>exposure</strong> to L•-1'S (Table 2) . In most of these studies<br />
the <strong>exposure</strong> index was sclf-reponed <strong>exposure</strong> to ETS at work, and the comparison<br />
group was porsons not exposed at work . Of the 12 studies, 7 were conducted in the<br />
United States, 3 in Asia, and 2 in Europe . L•levcn studies, including 6 U .S . studies,<br />
reported results for women, 4 studies, including 3 U .S . studies, reportcd results for<br />
men, and one U .S . study rcported results for rncn and women combined . Reported<br />
sex-specific relative risks ranged from 0 .68 to 3 .27, with 9 of 16 being above 1 .0 and<br />
the remaining 7 being 1 .0 or bclow . The authors of two U .S . femalc studies, IIrownson<br />
er al. (1992) and Stockwell er aL (1992), considered workplace ETS oxposure and<br />
reported no sigtti6cant increase in <strong>lung</strong> <strong>cancer</strong> risk, but did not present numerical<br />
results . Of the 16 reponed relative risks, we combined 15 by computing a weighted<br />
average of their logarithms, the wcights being the inverses of the variances of the log<br />
relative risks (the Butler rclutive risk of 0 .0 for males could not be ittcludcd in the<br />
mcta-analysir). The sunttnary relative risk for 12 of the 14 worldwide studies was 1 .01,<br />
with 95% confidence interval (0 .92, 1 .11) . The summary rr,.lative risk for 7 of the 9
Fontham rc mJ. (199I)<br />
Gas6nkd d d. (1983)<br />
Jancrich d at (199(l)<br />
Kabal aal Wwdv (1934)<br />
Kab .t(1990)<br />
Kalaodidi d d. (1990)<br />
Koo cl al. (1954)<br />
Lae e e/. (1986)<br />
Slamizu d o). (1983)<br />
Stock.rcU ct uL (1992)<br />
Wu e cL (1955)<br />
iVu•WdGamf d ol. (1990)<br />
Comparison jnwp<br />
Not exposcd at +rork<br />
F Workod with smokn for 1l+ years /vcvff workod .rith a smokcr<br />
M Worked with rmokcr for 1 t+ years T:cvrswwkcd wilh a smoker<br />
F E•cr exposed .t .wrk Ncrcr esporad at work<br />
F Exposed at work in pasl 25 years Not apowd anywhere in past 25 ycars<br />
F d M 150 paw.-ycarY' of workplaoc ocpoaurt No history of workplace capowre<br />
F Raufulr exposed .t work Not rcqularly cxpor«f at wvrk<br />
1,4 Rctulartp capo.xd at .+rork Not rcTulady cnposal at wvrk<br />
F Evcr cxpoad at work Ne .a espoa,d at work<br />
M Evcr exposed at work Nercr ctpoaal at .•ork<br />
F Exposed at work Not employed<br />
F Exposed at work only or at home and at work Not exposed al home or at work<br />
F ERpt»al at .rork Not caposod at work<br />
M Exposed at .rosk Not uposed al .•o+k<br />
F Someone al wotkplaoc snmka No one at .otkpiacc srnokcs, or<br />
su bjcct does not .ror k<br />
F Exposal at .rork No homc or .vork c.lwmnt<br />
F Extwwd .t nak Not expoxd at wotk<br />
F Ettporod .rt vrork Not exposed at wotk<br />
tn tcncril, no drntcd lunt<br />
pnccr risk »ociatod aitk<br />
ETS acpcmnc in the<br />
workplace<br />
1 .47<br />
0 .0<br />
0 .15. 14 .06<br />
1 .74 1 .03 . 1 .73<br />
0.93 0 .73 . 1 .13<br />
091 0 .60 . 104<br />
068 0 .32, 1 .47<br />
3 .27 1 .01, 10.61<br />
1 .00 0.49, 2 .06<br />
0.96<br />
0 .46, 2_10<br />
1 .39 0 .76 . 2 .54<br />
1_36 0.50, ) .73<br />
0.61 0.17 .2_33<br />
161 0.39, 6.60<br />
1_20 0.69, 2 .01<br />
No si6ni6nnl Sncmuc in risk for<br />
Norkplacc <strong>exposure</strong><br />
' ProDmct of numbcr of ytus sabjoct worked in a pmrtiadar place and oumbcr of rmokcrs in srmc raom or arca, tummal ovcr 12 mrnt rcc=nt jobi_<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
1.3 0.5 .3 .3<br />
1.1 0.9 . 1 .6<br />
w
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
314 ~ lrvots nrdu 1AYAnn<br />
U .S. studies was 0 .98 with 95''ro confidencc interval (0 .89, 1 .09) . Although we could<br />
not include the Arownsou ci al . (1992) and Stockwcil rr al . (1992) studies in the mctaanalyscs,<br />
since they did not report relative risk esumatrs for workplacc <strong>exposure</strong>, the<br />
authors' cotnutents, noted iu Tablc 2, indicate tha : including them would not change<br />
the conclusion that there is no epidetniologic evidence of an association between<br />
workplace ETS <strong>exposure</strong> and <strong>lung</strong> catlcer .<br />
In most of these studies, the referencc "nonexposed" group consisted of subjects<br />
who reportedly were not exposed to ETS at work, but may have b .:ccn czposed clsrwhere,<br />
such as in the homc . Subjects in the workplacc•cxposed group also may have been<br />
exposed to ETS elsewluru. 1f there werc an GTS-Jung eancer association, camParison<br />
betwecn these groups would tcnd to produce lower reported relative risks for F."15<br />
• workplace exposurc than would a comparison between groups having no natworkplace<br />
ETS <strong>exposure</strong>. Howcver, ttonoccuPational ETS <strong>exposure</strong> could not climittate the cffect<br />
of workplace <strong>exposure</strong> if a real association existed, so tlu combined results of the 12<br />
studies, showing no <strong>lung</strong> <strong>cancer</strong> risk elevation, stand as cvidcnce against tlte existence<br />
of a link between <strong>lung</strong> cattcer risk and E7S <strong>exposure</strong> .<br />
The fact that, with the cxccption of Chiua, summary relative risks from spousal<br />
stnoking <strong>lung</strong> <strong>cancer</strong> studies are higher than that from -orkplace ETS studies suppoRs<br />
the arguments of Section 2 that tlu rcponed spousal smoking risk elevation is a con•<br />
sequcnce of bins and confounding factors that are introduced by the spousal smoking<br />
study design . Workplace studies would not be subjeet to bias and confounding due to<br />
spousal concordance, and this is a likely explanation for the inconsistency between<br />
workplace and spousal smoking findings .<br />
The EPA (Farland, 1993) took the position that workplacc L•TS studies ean be<br />
disregarded for several reasons: (1) thcre arc fewer worldwidc workplace studies than<br />
spousal ETS <strong>exposure</strong> studies ; (2) workplaco <strong>exposure</strong>s arc much more variable over<br />
time than spousal cxposures, sinee study subjects and their co-wurkers typic :ally changc<br />
jobs severnl times during a lifetime, while ETS <strong>exposure</strong> fratU spousal smoking is<br />
relatively stable over time ; (3) presence of ha :e.ardous chemicals in somc workplaces<br />
can make interpretation of study results lnorc difficult than for spousal studics ; and<br />
(4) it can be inferred that if home b?S <strong>exposure</strong> can cause <strong>lung</strong> <strong>cancer</strong>, <strong>exposure</strong> "at<br />
comparable levels from other sources" can also incrcasc risk . These arguments do not<br />
withstand close examination . Iirst, 14 workplace E'i'S studies comprise an important,<br />
and relatively large, database that cannot be ignored . Second, the notion that workplace<br />
rTS <strong>exposure</strong>s are much more variable than "relativcly stable" spousal <strong>exposure</strong>s is<br />
unsupported spcculatiotl, In fact, the opposite may well be the case : it is hardly uncommon<br />
for people's smokius habits to change and for cohabiting partners to change,<br />
while there is no particular reason to suppose that subjects' workplace ETS <strong>exposure</strong><br />
would be markedly difCerent even if they changed jobs, particularly since the type of<br />
job and work environtnent are likely to be similar . Third, the proportion of subjccu<br />
in the workplace ETS studies who arc exposed to occupational <strong>lung</strong> carcinogens is<br />
likely to bc quite small, since 111c studies arc population-bascd, so it is hard to understand<br />
how workplaae ehcmicals could substantially bias an ETS-<strong>lung</strong> <strong>cancer</strong> association in<br />
these studics. In any case, if there wcrz such a bias, it %++ould surely tend to inflate an<br />
observed ETS risk, rather than tlu opposite . One would expcct smoking prevalences<br />
to be higher, not lower, in hazardous workplaces than in others since such vvorkplaces<br />
tend to employ bluc.collar workers . The I:PA's fourth point, that ETS <strong>exposure</strong> in<br />
workplaces is comparable to home <strong>exposure</strong>, and therefore if home exposurc can<br />
I<br />
I
could<br />
metart:,<br />
the<br />
:hange<br />
;tween<br />
ibjects<br />
wh ere,<br />
e bccn<br />
t ~>on<br />
Ir LTS<br />
•kplace<br />
; effect<br />
the 12<br />
;stcncc<br />
pousal<br />
pporu<br />
acontoking<br />
ie to<br />
~een<br />
:an be<br />
x than<br />
e over<br />
:hange<br />
ting is<br />
places<br />
~' ind<br />
t, "at<br />
do not<br />
)rtant,<br />
kplace<br />
ures is<br />
ly untange,<br />
)osure<br />
ype of<br />
.bj ects<br />
ens is<br />
ztand<br />
ion in<br />
ite an<br />
:ences<br />
;laees<br />
ire in<br />
can<br />
M<br />
ENVIRONML•hTAL TODACCO SMOKE AND 1,UNG CANCER 315<br />
cause <strong>lung</strong> <strong>cancer</strong>, so can workplace exposum, is not an arbument for dismissing tFte<br />
workplaec cpidcrniology at all . Rather, it simply avoids the question of why, if domestic<br />
and workplnce <strong>exposure</strong>s ttre comparable, thc combinmd workplace data do not indicate<br />
any ETS-<strong>lung</strong> <strong>cancer</strong> association .<br />
The fact that workplace studies pralucc a risk estimate that disagrees with the<br />
cstimatc derived from aggregated spousal smoking studies cannot be dismissed by<br />
making speculative assumptions about study design validity . The Icast that should be<br />
expected is that a diligent cffort be made to evaluate the reasons for the discrcpancy .<br />
Such an evaluation tnust seriously consider the possibility that it is the spousal smoking<br />
study dosign that is more scvcrely flawed . As well as many other potcntial confoundcrs,<br />
the spousal study design introduces sociocconomic status-mediated occupational nsk<br />
factors. Since there is a tentiency for smokers and their spouses to be oC lower socioeconomic<br />
status than nonsmoking couples, the spousal smoking stttdy design is likcly<br />
to confound ETS exposurc with employment in blue•collar jobs that involve more<br />
toxic <strong>exposure</strong>s . The workpiacc ETS study design avoids problems of spousal concordanec<br />
with respect to <strong>lung</strong> <strong>cancer</strong> risk factors and introduces (ewer potential biases<br />
and confounders than are present in the spousal study design . Thus, workplace ETS<strong>lung</strong><br />
<strong>cancer</strong> data are probably less flawed than are the spousal smoking data .<br />
4. CONCLUS(ONS<br />
Since probable effects of bias anci confounding have not been adequately accounted<br />
for in the spousal smoking-<strong>lung</strong> <strong>cancer</strong> epidemiologic studics, the EPA's conclusion<br />
that these studies support a r,tusal infertncc is not jttsti6ed,<br />
The aggregated workplace data indicate no ETS-<strong>lung</strong> <strong>cancer</strong> risk elevation, further<br />
undermining both a causal inference based on spousal smoking studies and the EPA's<br />
conclusion that ETS is a Group A carcinogen . The ETS-<strong>lung</strong> <strong>cancer</strong> epidemiologic<br />
data provide no scientific basis for government rzgulation of smoking in the workplace.<br />
REFERENCES<br />
BttowNSON, R. C., AI.AVAN)A, M . C. R ., Hetx, L• . T„ AND Loy, T . S, (1992) . Passive smoking and <strong>lung</strong><br />
nncer in nonsmoking women, dnt. J. Publfc Health E2, 1323-t330 .<br />
DUTLEA, T . L(198E) . The Re/utiwuhlp ojPaslire 5mok/n,t• to Various Ilcaltlh Outcon,rr amonj SeYrnrh<br />
Day Atlvcntirrt In Cul{'fornla, Ph .D, dissutation, Univenity of Glifornia, Los Ansele1<br />
FArZV.Nn, W . H. (1993) . Testimony before the U.S. Hotut ojRepuentatlres Subcommittee on Speclalty<br />
Cropsand Nutural Rerourres . ISBN 0-t6-04169E-1, pD, 99-120 . U .S . Governmcnt Printin=Oftice, Wmhington,<br />
1?C. '<br />
FownttiH. T. H ., CoRRPA, P ., et al. (1991) . Lung cnncsr in nonsmokin6 vromen : A muhitentcr nseoonuol<br />
ttudy. Canter L•pidemiol . Ilro+narkert Prr .. I, 35-43 .<br />
Ftantoruy, O . D, Pertrrt, D . R .. AND DAwol. R. D. (1983). Ptsnlcnco and correlatm of passive smokin` .<br />
Am . J. Public llealth 73, 401-A05 .<br />
GwttiaNKEL L, AvERtAe)t, 0„ AND JoU®ERT, L . (1985) . lnvoluntary smoking and <strong>lung</strong> <strong>cancer</strong>. A asceontrol<br />
study . Z NurL Concer Inrt . 75, 463-469.<br />
1At+ttueH, D. T ., TnoM['SON, W. D„ et el. (1990) . Lung <strong>cancer</strong> and exposurc to tobacco smoke in the<br />
household . N. ER .L J. Afrd sit R7l-.ctR<br />
KAar,T, G . C . (1990) . Epidcmiolopo studies of the rd .itionrhip txtwcen pasaive smokins and <strong>lung</strong> oncer . N<br />
ln 1990 olnnual Wnter Toxicolory Fonrm, pp . 1E7-201 . Tozicolo6y Forum, Waahin=ton, IUC . Ks,r1<br />
..T, G . C, ANO Wrxot:u . F. L. (19R4), Lung anccr in notumnkcti Cancer 51, 121L-1221, ~<br />
K& .wHDtut. A ., lUTSOUYAtrrrt, K ., et nl. (1990). Wuivo smokind and diet in the etiolo:y of tuns ancer r~<br />
atnonl non-smokera. Cancer Cauret Control 1, 1$-2t .<br />
80d t.ri-J_ St :L0 . b66'f "f Z'LMf TSLL-p65/Stb TL MEIN (1 D .J .-= I XDl NI SS .N01-rSNCD<br />
', I<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
-~ ~<br />
I
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
316 LJ :VOIS AND 1 .AYARD<br />
K1=2s, L M ., KI=U, R . G, AND CIUMNU, J, A . (1992). 1)iucNacia helwyen celf-reponed smoking<br />
and carbo :yhemotloltin : Au aualysis of thc sccond National 1lullh and Nutrition Survcy .,lrn . J . Yubhc<br />
11cal1h S2, 1026-1029 .<br />
KOO, L C, Ho, AND RYlah'DER, R. (1988}, life•Ltis(cry mrtslatcs of cnvironmental tnhacco satokc :<br />
A study on storuntokint Hong Kong C.hinesc wives with sctoking vcrsus nonsmokissg husMtnds . Soc . Sr.i .<br />
Ned . 26, 751-'/60 .<br />
Koo, L C .. 110, AND SAW . D, (19t1) . 1s paasivc smokin8 an added risk fanor for <strong>lung</strong> cuncer in<br />
C2tirszse women2 J. Erp, Clin. Canccr Ret. 3, 277-213 .<br />
1.AYAnD, M . W . (1992). Thc backtround adjustttlcnt in risk .uccunent of cnvironmenul tohscao smokc<br />
and <strong>lung</strong> ancer . Envfron, lru. ld, 453-461 .<br />
Lze- P . N . (1992), Environmental <strong>Tobacco</strong> S'make and Alortallry . KrrBcr AG, Daae1, Switxcrland,<br />
Lfil:, P . N ., CMASdbEALUN, J ., AND AWEhSON, M . R(1966) . Rclatianship of pusivc smoking to risk of<br />
<strong>lung</strong> canccr znd othcr amokint-associsscd diseJses, Br . J. Cancer 54, 97-105 .<br />
Ln M..sch-ttAND, 1 . ., Wltxiavs, L R ., st al. (1991) . Diaary pnturns of fcmalc nonsmokus with and without<br />
esposurc to environmcntaI tobaa:o amokc . Cancer Caures C:aural 2, 11-16 .<br />
PExtZ.STARtI. L• J ., I+IAkIN . G ., MASttN, A. V ., AND 8_:tiowlT7, N . L. (1992) . MiEdatsiGcation of .moktr.g<br />
status by self-reportcd cigercttc consumption . .1 n . Rrv . Resp . Dlseasr 145, 53-57 .<br />
SHILATA, A ., PALi~NWI-I{IiJ ., A ., Rosz . R . K., e ; al. (1992) . 1)ictary B-arotgne, cig .arcttc smokint, and<br />
<strong>lung</strong> oncer in men. Cancer Causes Conual3, 207-214 .<br />
StusRtzU, H ., MoRtssin'A, M ., MtzUNO . K ., et al. (1988) . A use control study of lun8 canccr in nonsmokinQ<br />
womcn . Tahoku J, Exp. afcd. 154, 319-397 .<br />
SIDNEY, S-, CA..N, B . J ., ANO Mk1kDMAN, G . D . (19n9) . Dicury intake of urotene in nonsmok<strong>ets</strong> with and<br />
without passivc smoking at homo . .4m, J. F.p,drmiol 129, 1305-1309 .<br />
SlroCxwr-a .t, H . G„ GowMAN, A . L, el uL (1992). finvironnunt.l tobacco cmoke smd <strong>lung</strong> canccr in<br />
'nonsmokin& womcn- J, Natl . Cancer lnut . 84, 1 a 17-1421 .<br />
'f~iQMT3DN, ll . H . . AND W .knuetoN, C) . M . (1993) . Dieury anJ mental hcalth diffcronces Isclwccn nevcrsmoken<br />
living in smokin8 houscbolJs and non-smnkine hou .eholds. J . Smok. Rel. Uis . 4. 203-211 .<br />
U .S . Environmcntal Proteztinn Altcncy (U .S- EPA) (19t6), Guidelitus for aranoEcn risk asxument, F'ed,<br />
Ret• 51, 33992-34003 .<br />
U S- Eavironmental I'rotuxiou Atcncy (U .S . E.PA) (1992) . Rcsptratory 1lealrh F,1Rctr ojPassirc SmokinR:<br />
L.unt Cancer and Olher hisorderz t•PA/600/6•90/006F, WashinFtun, DC-<br />
WAtltNKNL•CttT, 1 . . E ., Duasck, 0. L, et al. (1992) . Misclusi6cation of smoking sutut in shc CARDIA<br />
ssudy, A conlparison of sclf•rcpofl with sccuut cotinine levcls, .lrn- J. Yublic lfcalth 82, 33-36,<br />
Wu, A- IL, jiENDrxsoN, H . @., PtxE, M . C-, AnU Yu, M. C. (1985) . Smoking and other risk facwrs for<br />
<strong>lung</strong> cancrr in women . J. Natl. Cancer Intt. 74, 747-751 .<br />
WU-WlWAMS, A . H ., DAt, X . D„ 11tAT, W ., et al. (1990) . Lung <strong>cancer</strong> among women in north-ast Chinn .<br />
Dr. J. Canccr 62, 982-9R7 .<br />
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GENERAL COMMENTS<br />
The same criticisms that apply_to the spousal smoking risk<br />
estimates apply to the workplace risk estimates (no actual<br />
measurements of <strong>exposure</strong>, failure to account for sources of<br />
bias and for potential confounding factors, poor study design,<br />
weak reported associations) .<br />
As illustrated in Table 1, only two of the reported risk<br />
estimates<br />
majority,<br />
significant .<br />
are statistically significant . The overwhelming<br />
16 of 18 risk estimates, are not statistically<br />
Taken as a whole, these data do not support the<br />
existence of an association between workplace <strong>exposure</strong> to ETS<br />
and <strong>lung</strong> <strong>cancer</strong> risk in nonsmokers .<br />
As recently noted by LeVois and Layardl :<br />
The EPA' s<br />
workplaces<br />
therefore<br />
<strong>cancer</strong>, so<br />
fourth point, that ETS <strong>exposure</strong> in<br />
is comparable to home <strong>exposure</strong>, and<br />
if home <strong>exposure</strong> can cause <strong>lung</strong><br />
can workplace <strong>exposure</strong>, is not an<br />
argument for dismissing the workplace<br />
epidemiology at all . Rather, it simply avoids<br />
the question of why, if domestic and workplace<br />
<strong>exposure</strong>s are comparable, the combined<br />
workplace data do not indicate any ETS-<strong>lung</strong><br />
<strong>cancer</strong> association .<br />
1 . LeVois, M .E ., and Layard, M .W ., "Inconsistency Between<br />
Workplace and Spousal Studies of Environmental <strong>Tobacco</strong> Smoke<br />
and Lung Cancer," Regulatory Toxicoloay and Pharmacoloay 19 :<br />
309-316, 1994 .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
LeVois and Layard conclude :<br />
The fact that workplace studies produce a risk<br />
estimate that disagrees with the estimate<br />
derived from aggregated spousal smoking<br />
studies cannot be dismissed by making<br />
speculative assumptions about study design<br />
validity . . . . The workplace ETS study design<br />
avoids problems of spousal concordance with<br />
respect to <strong>lung</strong> <strong>cancer</strong> risk factors and<br />
introduces fewer potential biases and<br />
confounders than are present in the spousal<br />
study design . Thus, workplace ETS-<strong>lung</strong> <strong>cancer</strong><br />
data are probably less flawed than are the<br />
spousal smoking data . [authors' emphasis]
TABLE 1 : ESTIMATES OP pORKPLACE ETS EXPOSURE M LUNG CANCER RISlC IH NY)NS2SOICERS<br />
STUDY COUNTRY NUMBER OF CASES/CONTROLS GENDER EXPOSURE DEFINITION RISK ESTIMATES<br />
IN WORKPLACE ANALYSIS<br />
Brownson, et al ., USA not presented female "highest quartile" of workplace <strong>exposure</strong> L 2 (0 .9-1 .7)<br />
1992<br />
(432/1402 total) <strong>exposure</strong> in the workplace "no elevated <strong>lung</strong> <strong>cancer</strong> risk"<br />
Butler, 1988 USA 6 cases female worked with smoker for 11+ yr 147 (0 .15-14 .06)<br />
7 cases male worked with smoker for 11• yr 1 .72 (0_33-9 .04)<br />
Fontham, et al ., 1994 USA 609/1247 female ever exposed 1 .39 (1 .11-1 .74) •<br />
Garfinkel, et al ., USA 14/52 female <strong>exposure</strong> in last 5 years 0 .88 (0 .66-1_18)<br />
1985<br />
34/118 <strong>exposure</strong> in last 25 years 093 (0 .73-1 .18)<br />
Janerich, et al ., USA not presented both 150 person-years <strong>exposure</strong> 0 .91 (0 .80-1 .04)<br />
1990<br />
(191/191 total)<br />
Kabat & Wyader, 1984 USA 53/53 female current regular <strong>exposure</strong> 0 .68 (0 .32-1 .47)' '<br />
25/25 male current regular <strong>exposure</strong> 3 .27 (1 .01-10_6) "•<br />
Kabat, 1990 USA 44/111 female ever exposed at work 1 .00 (0_49-2 .06)<br />
37/105 male ever exposed at work 0 .98 (0 .46-2 .10)<br />
Kalandidi, ett al ., Greece 65/76 (est .) female "between extreme quartiles" of <strong>exposure</strong> 1 .08 (0,24-4 .87)<br />
1990<br />
some v- minimal <strong>exposure</strong> 1 .70 (0 .69-4 .18)'<br />
exnosed at work 1 .39 (0 .76-2 .54)'<br />
Koo, et al ., 1984 Hong 2/4 female exposed at workplace 0 .91 (not given)<br />
Kong<br />
Lee, et al ., 1986 Great 15/158 female ever exposed 0 .63 (0 .17-2 .33) "<br />
Britain<br />
10/59 male ever exnosed 1 .61 (0 .39-6 .60)"<br />
Shimizu, et ai_, 1988 Japan not presented female someone at workplace smokes 1_2 (not given)<br />
(90/163 total) 1 .2 (0 .70-2 .04)'<br />
1 .2 (0 .69-2 .01)'<br />
Stockwell, et al ., USA not presented female <strong>exposure</strong> at work "no statistically significant<br />
1992 increase in risk"<br />
(210/301 total)<br />
10921753<br />
0 1" BY 1Y,.--; Y{.J6z llZ<br />
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Wu, et al ., 1985 USA not presented female exposed at work 1 .3 (0 .5-3 .3)<br />
(29/62 total)<br />
Wu-Williams, et al ., China 415/602 female exposed a[. work 1 .1 (0 .9-1 .6)<br />
1990<br />
1 .22 (0 .95-1 .57)'<br />
10921753<br />
statistically significant<br />
1 .1 (0 .86-1 .41)'<br />
LeVois, M .E ., and Layard, M_W ., "Controversy Over Regulating Indoor Air Qualityc Environmental <strong>Tobacco</strong> Smoke," comment submitted to U .S .<br />
Occupational Safety and Health Administration, Docket H-122, No . 3-1067, March 19, 1992 .<br />
Lee, P .N ., Environmental <strong>Tobacco</strong> Smoke and Mortality . Basel, Karger, 1992 .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
2
Brownson, R .C ., Alavanja, M .C .R ., Hock, E .T ., and Loy, T .S .,<br />
"Passive Smoking and Lung Cancer in Nonsmoking Women," American<br />
Journal of Public Health 82(11) : 1525-1530, 1992 .<br />
In a study published in 1992, Drownson and colleagues<br />
reported on results of a case-control study of Missouri women who<br />
were lifetime nonsmokers or former smokers . This study is notable<br />
for its large sample size, as over 600 <strong>lung</strong> <strong>cancer</strong> cases were<br />
enrolled, more than 400 of whom were self-reported lifetime<br />
nonsmokers . The authors wrote :<br />
In general, there was no elevated <strong>lung</strong> <strong>cancer</strong><br />
risk associated with passive smoke <strong>exposure</strong> in<br />
the workplace (not shown in table) . Only<br />
lifetime nonsmokers showed a slight increase<br />
in risk at the highest quartile of workplace<br />
<strong>exposure</strong> (OR = 1 .2 ; 95% CI = 0 .9, 1 .7) .<br />
As the above paragraph indicates, these authors failed to present<br />
their overall risk estimate for workplace smoking, which was<br />
apparently not statistically significant . The risk estimate that<br />
was presented, that is, the one for the most extreme self-reported<br />
<strong>exposure</strong> category, was also not statistically significant .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
Objectisrs . The causes of <strong>lung</strong><br />
<strong>cancer</strong> among nonsmokers are not<br />
dearly understood . To funher evaluate<br />
the relation bctwecn passive<br />
smoke expxosure and <strong>lung</strong> canxr in<br />
nonsmok7ng women, w•c conductcd a<br />
population-based, case-control<br />
studr .<br />
Afer,'tods . Casc patients<br />
(n = 618), idcntined throueh the Missouri<br />
Cancer Repstry for thc period<br />
1986 through 1991, included 432lifctime<br />
nonsmokers and 1So cx-smokers<br />
who had stopped at least 15 years<br />
before diaposis or who bad smoked<br />
for less than 1 pack-year . Control<br />
subjeeis (n = 1402) were selected<br />
from dri4'er's license and Medicare<br />
files .<br />
Restllu . No increased risk of<br />
<strong>lung</strong> <strong>cancer</strong> was associated with<br />
childhood passive smoke e .rposure .<br />
Adulthood analyses showed an increased<br />
<strong>lung</strong> <strong>cancer</strong> risk for lilctime<br />
noasznokers with <strong>exposure</strong> of more<br />
than 40 pack-years from all housebold<br />
roembers (odds rat)o (ORJ = 13 ;<br />
95% confidence interval (CI) = 1 .0,<br />
1-8) or fxom spouses only (OR = 1 .3 ;<br />
95`'o CI s 1 .0, 1 .7) . When the tuneweighted<br />
product of pack-ycars and<br />
average bours ccposcd pcr day was<br />
considered, a 305'o excess risk was<br />
shown at the highest quamk of <strong>exposure</strong><br />
among lifetirne nonsmokers .<br />
Cwtclunoru. Qurs and other recent<br />
studies suggest a small but consistent<br />
increased risk of <strong>lung</strong> caneer<br />
from passive snnoidng . Compr-ehensivc<br />
actions to limit smot^:ng in public<br />
places and worksitcs are weU-advised<br />
. (Am J Public Health .<br />
1992 ;82• 1525--1530)<br />
Passive Smoking and Lung Cancer in<br />
Nonsmoking Women<br />
Ross C. E?row7uori, P1tD, Michael C R. Alavanja, DrPlf Edward T. Hoa-, BS,<br />
and Timo :hv S. Loy', hfD<br />
Introiurtion<br />
Although most <strong>lung</strong> <strong>cancer</strong> occurs in<br />
smokers, approximately 9c7c to 13% of<br />
<strong>lung</strong><strong>cancer</strong> cases in US women develop in<br />
lifetime nonsmokers .'-S The causes of<br />
<strong>lung</strong> <strong>cancer</strong> in nonsmokers have not been<br />
wideiv studied, but probably comprise a<br />
diverx set of factors including eenctics,<br />
occupational factors, radon <strong>exposure</strong>,<br />
diet, and a history of nonrr,alignant <strong>lung</strong><br />
discasc .<br />
In addition to these risk factors, the<br />
etioloac role of passive smoke <strong>exposure</strong><br />
has received increastnQ scrutinv over the<br />
past decade . Numerous studies"0 have<br />
suggested an elevation in <strong>lung</strong> <strong>cancer</strong> risk<br />
for nonsmoking females who live with a<br />
smoker, with a summary excess risk of<br />
appro.tiunatcly 30`-c .=t•= However, several<br />
recent studiest= -' have shov .n no<br />
increased <strong>lung</strong> <strong>cancer</strong> risk due to spousal<br />
smoking .<br />
Limited evidence1-=6 also suggests<br />
that <strong>exposure</strong> to passive smoke in cht3dhood<br />
may inacase risk of <strong>lung</strong> <strong>cancer</strong> . For<br />
example, a recent case-control study from<br />
New York found that household <strong>exposure</strong><br />
to tobacco smoke during childhood of 25<br />
or more smoker-years' duration was associated<br />
with a doubling of <strong>lung</strong> <strong>cancer</strong><br />
risk .'a<br />
Most previous studies of passive<br />
smoking and <strong>lung</strong> <strong>cancer</strong>, although suggestrve<br />
of a positive effect, have had several<br />
deficiencies . Thesee deficiencies includc<br />
sample sizes insufficient to singly<br />
demonstrate significant elevations in risk,<br />
limited data or, passive smoke <strong>exposure</strong> in<br />
both childhood and adulthood, and lack of<br />
histologic revicw of cases to venfy <strong>lung</strong><br />
<strong>cancer</strong> diagnosis and to allow analyses by<br />
cell type .<br />
To more fuUy evaluate the rclationship<br />
betwecn <strong>lung</strong> <strong>cancer</strong> and passive<br />
smoke <strong>exposure</strong> in childhood and adulthood,<br />
we conducted a IarQe case-control<br />
study of <strong>lung</strong> <strong>cancer</strong> among nonsmoking<br />
womcn .<br />
Methods<br />
Case Group<br />
Case patients were identified through<br />
the Missouri Cancer Registry, which is<br />
maintained by the Missouri Department of<br />
Health . The Reaistry began collecting<br />
data on incident <strong>cancer</strong> cases from public<br />
and private hospitals in 19-72, and hospital<br />
reporting was mandated by law in 1984 .<br />
Registry rcporting procedures havc been<br />
discussed in more detail elsewhere .= To<br />
ensure complete reponing of <strong>lung</strong> <strong>cancer</strong><br />
cases in women for the current study, we<br />
had Registry staff complete special case<br />
ascenainment visits to participating hospitals<br />
. The case series included White<br />
Missouri women, aged 30 to 84 years, who<br />
were diagnosed with primary <strong>lung</strong> <strong>cancer</strong><br />
betwten January 1986 and June 1991 . Selection<br />
was limited to Whites because of<br />
small numbers of other racial/ethnic<br />
Ross C . Brownson is with the Division of<br />
C}uortic Diseasc Prevenhon and Health Pro<br />
motion, Missouri Deparanent of Health, Columbia,<br />
Mo. Michael C . R . ?.lavanja iswith the<br />
Epidemiology and Biostatistiec Progrant, National<br />
Cancer lrutitute, Roekvt7le, Md. Edward<br />
T . Hock is with Information Management Ser .<br />
vices, Rockvt7le, Md . Ttnwthy S . Loy is with<br />
the Pathology Deparunent, Universiry of Missouri<br />
School of Mcdicine, Columbia, Mo .<br />
Requests for reprints should be sent to<br />
Ross C. Brownson, PhD, Division of Chronic<br />
Disease Prevention and Health Promotion,<br />
Missouri Dcpartrnent of Health, 201 Business<br />
Loop 70 West, Columbia, MO 6520.3 .<br />
This paper was submitted to the Joumal<br />
February 19, 1992, and aecepted with revisions<br />
August 12, 199? .<br />
Novembtr 1993, Vol . $2, No. 1I Amcrxan Joumal of Public ltcalth 1525<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
groups . The case group included both li.fetime<br />
nonsmokers and ex-smokers who<br />
had stopped smoking at least 15 years before<br />
diagnosis or who had smoked for less<br />
than l pack-year . From the 3475 cases of<br />
<strong>lung</strong> <strong>cancer</strong> in women reported for the<br />
study period, 650 eligible patients were<br />
identified . Physicians denied interview<br />
perrnission for 24 (4%) of these padents<br />
and an additional 8 women (1 e/o) refused to<br />
be intervicwed . The final case group included<br />
432 (70%) lifetime nonsmokers and<br />
186 (30rro) ex-smokers . Of the 618 case<br />
intetvic.vs, 216 were conducted with patients<br />
thernsclves and 4-02 were conducted<br />
with surrogates because the patient was<br />
too IIl to be interviewed or had die .d . Of the<br />
surrogate interviews, 105 (26°lc) were condueted<br />
with the patient's spouse and 297<br />
(74%) were conducted with another rclative<br />
(c .g„ odspring or sibling) .<br />
HLirOlCrgIC COrt f17rnG2rZOn of Cases<br />
Tissue slides were reviewed for histolopc<br />
verification for 468 (76CC) of the 618<br />
cases . Slides for these cases were examined<br />
simultaneously by three pathologists<br />
(T .L, E .I ., and J .M .) using a multiheaded<br />
microscopc without knowledge of the refcrring<br />
pathologist's diagnosis . In surgical<br />
spedmens, consensus diagnoses were obtained<br />
v.ith the critcria outlined in the<br />
World Hcalth Or¢anization classification<br />
scheme .=9 Rfien orily cytologic material<br />
was available, consensus was obtained<br />
with standard cytologic critcria .30<br />
Connrol Group<br />
A population-bascd sample of control<br />
subjects was ascertained by two mcthods<br />
. For women younger than 65 years, a<br />
sample of state driver's license files was<br />
provided by the Missouri Depanment of<br />
Revenue . For women aged 65 to 84 years,<br />
conurol subjecu were generated from the<br />
Health Care Finance Administration's<br />
rostcrof Medicare recipients .3t On the basis<br />
of age dismbution of <strong>lung</strong> <strong>cancer</strong> eases<br />
previously reponed to the Registry, the<br />
final control group was matched by aee<br />
group to case patients at an approximaLe<br />
2 .2 to I ratio . All control subjects were<br />
interviewed direct}y . Of the 1862 potentially<br />
elig1le control subjects, 335 (18%)<br />
refused the initial screening interview and<br />
125 (7%) of those screened and found eligpble<br />
rcfused the fttll interview . The fuial<br />
control group numbered 1402 .<br />
Quesrionnafre Design and<br />
Adminiriration<br />
Telephone interviews were con•<br />
ducted by trained interviewers . The first<br />
phase of the interview- consisted of a<br />
screening qucstionnaire to verify the age,<br />
race, and smoking status of case patients<br />
and control subjccu . For subjects who<br />
were screened and found cligiblc and who<br />
ag7ecd to the full interview, the study<br />
questionnaire consisted of sections on residential<br />
history, passive smoke expostire,<br />
personal health history, family health history,<br />
reproductivc history, occupational<br />
<strong>exposure</strong>, and dietary factors .<br />
Questions ragarding passive smoking<br />
focvsed on <strong>exposure</strong> in both cht7dhood (17<br />
years and younger) and adulthood (18<br />
years and older) . For each time period,<br />
respondents were questioned about the<br />
sourcee of <strong>exposure</strong> (e .g ., a parent or<br />
spouse) . Afrer an indMdual source was<br />
determined, a series of detailed questions<br />
were asked on the typc of tobacco used,<br />
duration of <strong>exposure</strong>, intensity of <strong>exposure</strong>,<br />
and avcraee number of hours per<br />
day exposed . These questions were partially<br />
modcled aftcr those dcvcloped by<br />
Wynder et al .3- In addition to quantitative<br />
estimates of <strong>exposure</strong>, respondents were<br />
asked to cuimate a perceived level of <strong>exposure</strong><br />
during childhood and adulthood<br />
("During most of your adult years, would<br />
you say that vour average <strong>exposure</strong> to<br />
smoke at home w•as liaht, modcrate, or<br />
heavy?") .<br />
Ana lyses<br />
Odds ratios (ORs) and 95% confidence<br />
intervals (Cls) were calculated .vith<br />
multip)c logistic regression .» The lincariry<br />
of trends in risk according to level of<br />
passive smoke <strong>exposure</strong> was evaluated<br />
with Mantel's one-tat7cd test .s' We initially<br />
examined numerous potential confounding<br />
factors . These included age, active<br />
smoking (for ex-smokers), history of<br />
previous <strong>lung</strong> diseases, dietary beta carotene,<br />
and dictary fat . Of these variables,<br />
only age, acm e smoking, and previous<br />
<strong>lung</strong> disease appeared to confound passive<br />
smoking findings ; therefore, the results<br />
presented are adjusted for these factors<br />
.<br />
Histologic r,vpe-specific analyses<br />
were conducted for cases for which consensus<br />
diagnoses were determined . Thesc<br />
analyses were undertaken bccause eariier<br />
studiess•tb-m have shown variations in risk<br />
by cell type, and biological mcchartisms<br />
have been proposed that might account<br />
for these variations .20•u<br />
Results<br />
Sociodcmographic and smoking-rclated<br />
charaeterisda of case panents and<br />
control subjects have been presented in<br />
dctail elsewhcre .M In brief, the average<br />
ages of case patients and control subjects<br />
were 71 .5 years and 69 .9 years, respcct'rvcly<br />
. The two groups were also comparable<br />
on level of education and income .<br />
Among ex-smokers, the median interval<br />
since cessation was 24 years, and average<br />
smoking intensity was 16.4 cigarettes per<br />
day .<br />
Tnere was little evidence of incTeased<br />
<strong>lung</strong> <strong>cancer</strong> risk associated w~ith passive<br />
smoke <strong>exposure</strong> in childhood (Table 1) .<br />
This lack of association was apparent for<br />
both the dichotomous variables (never vs<br />
evu exposed) and quantitative measures<br />
such as pack-years . The only suggestion<br />
of elevated risk was noted for less quantitative<br />
<strong>exposure</strong> variablcs (not shown in<br />
table) . Among lifetime nonsmokers, an increased<br />
risk of <strong>lung</strong> <strong>cancer</strong> was shown for<br />
those reporting moderate (OR = 1 .7 ; 95%<br />
CI = 1 .1, 2 .5) and heavy (OR = 2 .4 ; 95%<br />
C] = 1 .3, 4 .7) <strong>exposure</strong> to passive srrioke<br />
in childhood . Risk estimates for most<br />
childhood <strong>exposure</strong> variables were<br />
slightly higher (approximately 20% to<br />
30%) when analyses included otrly direct<br />
interviews, although none achieved statistical<br />
significance .<br />
An clevate.d isk of <strong>lung</strong> <strong>cancer</strong> was<br />
identifiui for lifetime nonsmokers at the<br />
lughest quan0e of passive smoke <strong>exposure</strong><br />
in adulthood (Table 2) . At an exposurc<br />
level of ntore than 40 pack-ycars, Iifetime<br />
nonsmokcrs showed a 30% increase<br />
in risk whether the source of <strong>exposure</strong> was<br />
all household members or spouses only .<br />
Similarly, when the product of pack-years<br />
and average number of hours exposed per<br />
day was considered, <strong>lung</strong> <strong>cancer</strong> risk for<br />
lifetime nonsmokers was elevated for the<br />
highest <strong>exposure</strong> quanile whether the<br />
source was all household members<br />
(OR - 1 .3 ; 95% CI = 1 .0, 1 .8) or spouses<br />
only (OR = 1 .3 ; 95PC CI = 1 .0, 1 .7) .<br />
Among lifetime nonsmokers, a positive increasing<br />
trend in risk was noted for packyears<br />
(P = .06) . Passive smoking-related<br />
risk estimates for adulthood <strong>exposure</strong>s<br />
were slightly lower for all subjccts (i .e .,<br />
both ex-smokers and lifetime nonsmokers)<br />
than for lifetime nonsmokers alone,<br />
although the same general elevations in<br />
risk were notcd . When analyses were limitcd<br />
to direct intcrvinvs, no clear pattem<br />
of increase or decrease in risk estimates<br />
was apparent . Regarding less quantitative<br />
<strong>exposure</strong> variables, elevated risk was<br />
shown for all subjects (OR = 1 .7 ; 95%<br />
0 = 1 .1, 2 .6) and for lifetime nonsmok-<br />
15:b American loumal of Public Health November 1992 . Vol . 82, No . 11<br />
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TABLE 1-A.dl" ttd Odds RatSat (OR)` and 95% Confidence lrrtavata (CO fw the Relatlonosure<br />
during Chtldhood and Lun9 Catxc-r In Wornen, Mlsaourl, 1986 through 1991<br />
~11 ,,SL~.)jedSb<br />
LIf2tlrnC NLYSSlTtOk9f7<br />
Source of E)posure No . Cases No . Ccrmots OR 95% Cl No . Cases No. Corttrds OR 95% Cl<br />
Al1 hauatlol6 members<br />
t,}ew 430 928 1 .0 323 802 1 .0<br />
Ever 185 472 0.8 0 .7, 1 .1 108 364 0,8 0.6, 1 .1<br />
Ggarette pedc-years<br />
0 430 926 1 .0 323 802 1 .0<br />
>0-15 42 129 0.7 0 .5, 1 .0 27 104 0 .7 0.4 .1 .1<br />
>15-25 31 119 06 0 .4,0 .9 20 91 0 .6 OA,1 .0<br />
>25 34 117 0.7 0.4, 1 .1 21 87 0 .7 0,4, 12<br />
Parents onty<br />
Never 489 1021 1 .0 357 877 1 .0<br />
Ev¢r 126 379 0,7 0 .5, 0.9 74 289 0 .7 015, 0.9<br />
Ciyaretie padc-years<br />
0 489 1021 1 .0 357 877 1 .0<br />
>0-15 19 90 0.4 0 .3, 0.7 12 70 0 .5 0 .2, 0.8<br />
> 15-25 27 118 0.5 0 .3, 0.7 17 87 0S 0 .3, 09<br />
>?5 33 99 0.7 0 .5, 1 .1 21 74 0 .8 0 .5, 1 .4<br />
°,•dNLzted ror .9e, nmory of pr er.+xis r.rig c3seRSa, and .c:tr-e emo+orq ( ad v.ixecs ort4<br />
`lrx7udea kfaarne np-ampRa-t end ax-rnoknrs wt)o had stapped at leasc 15 ywrs tx4 .xe diaasosa or wttio had srrnked !or 4eaa tnan 1 prScyear,<br />
ers (OR = 1 .8 ; 95% CI = 1 1, 2 .9) who<br />
reported heavy <strong>exposure</strong> to passive<br />
smoke .<br />
In general, there was no clevatcd <strong>lung</strong><br />
<strong>cancer</strong> risk associated with passtvc smoke<br />
<strong>exposure</strong> in the workplace (not shoµr in<br />
table) . Only lifetime nonsmokers showed<br />
a sllght increase in risk at the highest quartile<br />
of workpface <strong>exposure</strong> (OR = 1 .2 ;<br />
95% CI = 0 .9, 1 .7) .<br />
Among the 4,58 <strong>lung</strong> <strong>cancer</strong>s that were<br />
verified histologjcal}y, the predominant cell<br />
types were ader>ocaxcinoma (62 .49c), other/<br />
mixed cell types (25 .2%), squamous cell carcinoma<br />
bronchioah-colar carcinoma<br />
(4 .11,1), and small cell carcinoma (2S5`c) .<br />
The other/mixed cell type category con-<br />
sisted mainly of large cell <strong>lung</strong> <strong>cancer</strong>s,<br />
though these lacked suff•icient pathologic<br />
evidence for precise classincation . Table 3<br />
presents results of cell typc-specific artalyses<br />
for adulthood <strong>exposure</strong>s . Elevated risk<br />
was shown for otherhnixed cell typcs at<br />
more than 40 pack-years of exposurc<br />
(OR = 1 .6 ; 95% CI = 1 .0, 25). Akhouzh it<br />
was based on small numbers, a risk estimate<br />
of 1 .7 was observed for small cell carcinoma<br />
at the highest level of <strong>exposure</strong> .<br />
We also examined risk among<br />
women who had been exposed to passive<br />
smoke in both childhood and adulthood,<br />
in childhood but not in adulthood, and in<br />
adulthood but not in childhood .7lure was<br />
no evidence of interaction between <strong>exposure</strong><br />
during the two periods .<br />
Discussion<br />
Our study suggests that <strong>exposure</strong> to<br />
high levels of environmental tobacco<br />
smoke in adulthood incTCascs the risk of<br />
<strong>lung</strong> <strong>cancer</strong> in nonsmokers . Exposure of<br />
more than 40 pack-ycars' duration increased<br />
the risk of <strong>lung</strong> <strong>cancer</strong> among nonsmokers<br />
by approximately 30% . 'I"ttis relationship<br />
%vas consistently demonstrated<br />
among lifetime nonsmokers whether the<br />
<strong>exposure</strong> variable was pack-years or the<br />
time-weighted product of pack-years and<br />
average number of hours exposed per day .<br />
Our findings are similar to those of another<br />
large study of <strong>lung</strong> <strong>cancer</strong> in nonsmoking<br />
womenm that identificd an OR of approxunately<br />
1 .3 due to <strong>exposure</strong> to greater than<br />
40 pack-years of spousal smokingIn earlier studies, the most commonly<br />
reported index of passive smoking<br />
<strong>exposure</strong> has been the presence or abscnceofasmokingspouse<br />
. Inourdataset,<br />
no elevated risk was noted for this variable<br />
. Since our study was limited to<br />
women, part of the difference between our<br />
findings and those of earlier studies may<br />
be due to differences in the effects of passive<br />
smoke <strong>exposure</strong> by gender . -Ilx National<br />
Rcscarch Council's summarv of 13<br />
studics=t found overall relative risks of<br />
<strong>lung</strong> <strong>cancer</strong> in nonsmokers due to spousal<br />
smoking of 1 .32 for women and 1 .62 for<br />
men (although the estimate for men was<br />
based on few cases) . It is possible that<br />
men are exposed to other factors (e .g .,<br />
occupational <strong>exposure</strong>s) that may interact<br />
w~ith passive smoke <strong>exposure</strong> to increase<br />
ruk above that observed in women . Pruencc<br />
or absence of a smoking spouse is a<br />
relatively erudc measurc of passive smoke<br />
<strong>exposure</strong>, with a potential for wide variabtliry<br />
in acrual <strong>exposure</strong> . It was noted in<br />
one survey, for example, that 47% of<br />
women married to smokers reported zero<br />
hours of passive smoke <strong>exposure</strong> at<br />
homa.s' It has also been shown that considering<br />
spousal <strong>exposure</strong> alone may underestimate<br />
total household passive<br />
smoke exposurc .M Another factor that<br />
may account for the differences in <strong>lung</strong><br />
<strong>cancer</strong> risk due to spousal smoking between<br />
our study and earlier studies may be<br />
time trends in smoking patterns . The de-<br />
clining prevalence of smoking among<br />
men39 has probably resulted in decreasing<br />
years and perhaps levels of <strong>exposure</strong> to<br />
passive smoke in the home among nonsmoking<br />
women whose husbands smoke,<br />
Contrary to the findings of two earlier<br />
case-control srudies,'•26 our data showed<br />
no evidence of excess <strong>lung</strong> canccr risk due<br />
to passivc smoke <strong>exposure</strong> in childhood .<br />
The risk of <strong>lung</strong> <strong>cancer</strong> due to childhood<br />
passive smoking may have some analogy<br />
to risk among ex-smokers . After 10 years<br />
of abstinence, the <strong>lung</strong> <strong>cancer</strong> risk for exsmokers<br />
declines to 3oro to 50% of the risk<br />
for continuing smok<strong>ets</strong> .p Siuu7arly, <strong>lung</strong><br />
<strong>cancer</strong> risk due to passive smoke <strong>exposure</strong><br />
in childhood may decline by adulthood,<br />
espccially in the absence of adult-<br />
Novemtxr 1992, Vol . 82, No. 11 Amenean loumal of Public Health 1527<br />
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iI ''wt•• *~aw'..rrr .-,~ ;r,r,wt.d nl~YBi~W 3L~ ,d6<br />
~- - -~_<br />
Brv .+nsan ct .I .<br />
TABLE 2-Adlustrd Odcta RaUoa (Ofi)' and 96% Cortitdcnce Intervals (CR for t1x Relation,chlp txtween Paacatve Srnoke Exposurrc<br />
duMg Adulthood and LLN Cancer In Wonxn, Mlasourt, 1966 throagh 1991<br />
A1 SubieCS° LJkti-ne Norrsrnokers<br />
Souce of Exposvre No . Cases No . Corwnls OR 95% CI No . Cases No. Contro(s OR 95% CI<br />
AD taus*)O~d members<br />
Never 221 527 1 .0 170 470 1 .0<br />
Eyer 394 873 1 .0 0.8, 12 261 896 1 .1 0 .8, 1 .3<br />
tte -YearS<br />
0 221 527 1 .0 170 470 1 .0<br />
>0-15 88 234 0 .9 0,6, 1 .2 56 181 0 .9 0 .6 .1 .2<br />
> 15-4A 91 261 0 .8 0.6, 1 .0 52 199 0.9 0 .6 .1 .2<br />
>40 146 264 1 .3 1 .0, 1 .6 107 217 1-3 1 .0, 1 .8<br />
C'k-ette pack-years x hotrsJday`<br />
0 221 527 1 .0 170 470 1 .0<br />
> 0-50 90 261 0 .8 0 .6, 1 .1 63 206 0 .9 0 .6, 1 .2<br />
>50-175 89 246 0 .8 0 .6, 1 .1 58 189 0 .9 0 .6, 12<br />
> 175 124 238 1 .2 0 .9, 1 .6 92 192 13 1 .0, 1 .8<br />
tJ, .wer 287 650 1 .0 213 568 1 .0<br />
Erer 328 750 0 9 0 .8, 1 .1 218 598 1 .0 0 .8, 12<br />
Ggatene pack-years<br />
0 287 650 1 .0 213 588<br />
>0-15 58 166 0.7 0 .5, 1 .0 32 128 0.7 0.5, 1 .1<br />
> 15-40 81 258 0 .7 0 .5, 09 54 200 0.7 0 .5, 1,0<br />
>40 150 266 12 0 9, 15 110 216 1 .3 1 .0, 1 .7<br />
Cigarelte pack-years x hours/dey`<br />
0 267 650 1 .0 213 568 1 .0<br />
>0-50 64 201 0 .7 0 .5,0 .9 4t 161 0.7 0 .5, 1 .0<br />
>50 175 81 237 0 .7 05, 1 .0 52 183 0.8 0 .5, 1,1<br />
> 175 126 241 1 .1 09, 1 .5 94 193 1 .3 1 .0, 1 .7<br />
`A4 .s1a7 lor aqe, hmpy of p(ev,a .a lu)g dsewe, ard acttve smo+~Yq (al sut~ec's orYy; .<br />
°SrrJLqect Itenme normxyKers ar4 ex-sndcers who had ntppw i3 Vaa :A 15 yea-s Deta'e d egrOOS or wM had srnc4utl tor Ita3 thw i pack-ysar,<br />
`The proad of lotai pack yea•s anf everage nurber Of hours ctaosed per cay to pamrve urq-e n the hortA .<br />
TABLE 3-AtSJusted tOdds Ratloa (Oft)' and 95% Corrfidenae IMerrala (CI) for Ux Re{rrionshlp btrtwesn Pasalve Smoke Exposure<br />
cturktg Adt>nftood and LuN Cancer In Women, by Hlstolo9lc Type, 6,Ussotxi, 1986 thrwph 1491<br />
Ade)ocercr~ Other/Maed SquamaJS Ce4 Srnall Cell<br />
Source of Epostxe No, Cases OR 95 % Ct FJo . Cases OR 95% CI No . Cases OR 95% C1 No . Cases OR 95% Cl<br />
!+l hot~old members<br />
Never 100 1 .0 37 1 .0 10 1 .0 3 1 .0<br />
Ever 192 1 .1 0 .8, 1-5 80 12 0 .8 .1 .6 16 0 .7 0 .3 .1 .7 9 12 0 .3, 4 .5<br />
Cigwete pack-ya-<br />
0 100 1 .0 37 1 .0 10 1 .0 3 1 .0<br />
>0-15 49 1 .1 0.8, 1 .6 17 1 .0 05, 1 .7 4 0 .7 0.z 22 1 OS 0 .0 .4 .6<br />
>15-40 48 0.9 0 .6, 1 .4 18 0 .8 0 .5, 1 .6 5 0 .7 02, 20 2 0A 0 .1, 4 .8<br />
>40 61 12 0 .8, 1 .7 31 1 .5 0 .9, 26 2 0 .3 0.1 .1 .4 5 22 0 .5, 9 .7<br />
Spoc.6C Only<br />
Nevet 131 1 .0 48 1 .0 14 1 .0 4 1 .0<br />
Ever 161 1 .0 0.8 .1 .3 69 1 .1 0.7, 1 .7 12 0 .6 0 .2, 1 .3 8 1 .2 02,41<br />
CiQarette pack,/ears<br />
0 131 1 .0 48 1 .0 14 1 .0 4 1 .0<br />
>0-15 36 1 .0 0.7, 1 .6 10 0 .7 0,4, 1 .5 3 0 .7 02, 2.4 1 0.7 0 .1, 6 .6<br />
>15--40 41 0 .8 0 .5,1 .1 16 0.8 0.4,1 .4 6 0.8 0 .3,2.1 3 12 03,5 .6<br />
>40 62 1 .1 0.8, 1 .5 34 1 .6 1 .0, 25 2 02 0 .1, 1 .1 4 1 .7 0 .4, 7 .0<br />
'Adxntod ta .qe, hmory at pre~ 1ng doease, arw azfY.v cno+cns,<br />
hood <strong>exposure</strong> . In addition, there may be assessment of <strong>lung</strong> <strong>cancer</strong> risk due to pas- especially problematic when a large perlow<br />
reliabt7ity for quantitative measures sive smoke <strong>exposure</strong> in chiJdhood panic• centaee of surro¢atc inteniews are con-<br />
(intensity and duration) of passrvc smoke ularly difficult . Reliabiliry and validlty of ducied (as in our study) . Partially because<br />
<strong>exposure</strong> in childhcad,•1•'= which makcs measures of childhood <strong>exposure</strong> may be of these limitations, few studies of child-<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
hood passive smoking and <strong>lung</strong> <strong>cancer</strong><br />
have been conducted, and further research<br />
in this area is needed .<br />
Our analyses by histologic type<br />
showed the largest increase in risk for<br />
other/mixed cell types and, although the<br />
estimate was basedon very small numbers,<br />
for small celU carcinoma . Previous studies<br />
are inconsistent and often lacking in sample<br />
size when evaluating risk by cell type .<br />
Garfin}xl ct a1 .10 found an elevated risk for<br />
squamotis cell carcinoma and for other/<br />
mixed cell typu . Othcrss•ta have observed<br />
larger elevations for squamous and small<br />
cell carci.noma than for adenocareinoma .<br />
In contrast, Wu et al .tt and Fontham ct<br />
al .m found larger increases for adenocarcinoma.<br />
An additional difficulry in evaluating<br />
previous studies of pa,ssive smoking and<br />
<strong>lung</strong> eancer by histologic type is that few<br />
studies have conducted systematic pathology<br />
reviews to verify ccll type .<br />
Our study has several major saengths .<br />
Thc:,c include the large sample size-one of<br />
the largest serics of nonsmofing <strong>lung</strong> <strong>cancer</strong><br />
cases to date . In addition, we had relavvely,<br />
hi.gh response rates fiom bnth case patients<br />
and control subjects . Finally, we conductcd<br />
a pathology review of cases .<br />
The main limitation of our stvdy is<br />
the possibiLty of recall bias for passive<br />
smoke <strong>exposure</strong> variables .'The less quantitative<br />
measures of passive <strong>exposure</strong><br />
(i .e ., light, moderate, or heavy <strong>exposure</strong>)<br />
resulted in larger risk estimates than more<br />
quantitative estimates such as pack-years .<br />
Because there is no way to confirm previous<br />
passive smoke <strong>exposure</strong>, it is difficult<br />
to determine the best index for estimating<br />
<strong>exposure</strong> . However, we found that<br />
<strong>lung</strong> <strong>cancer</strong> ritk due to adulthood passive<br />
smoke <strong>exposure</strong> was elevated at the highest<br />
quartile of <strong>exposure</strong> whether we used<br />
a more quantitative (e .g ., pack-years) or<br />
less quantitative (e .g ., heavy <strong>exposure</strong>)<br />
variablr, .<br />
Another possible source of bias in our<br />
study is the large number of surrogate interviews<br />
for cases . Earlier studies,M-'s<br />
however, have show-n relatively close<br />
agreement on most passive smoke <strong>exposure</strong><br />
variables as reported by subjects and<br />
spouses . We found fairly minor alterations<br />
in risk estimates when analyses were restricted<br />
to directly interviewed c.2ses . In<br />
addition, we compared sociodemographic<br />
characteristics of direct and surrogate<br />
case-group interviews and found close<br />
agreement for most variables . As one<br />
might expect, the exceptionwas age ; there<br />
was a tendency toward more younger case<br />
patients in direct intervicw5 .<br />
In summary, our study and others<br />
conducted during the past deeade suggest<br />
a small but consistent elevation in the risk<br />
of <strong>lung</strong> <strong>cancer</strong> in nonsmokers due to passive<br />
smoking .'Ihe prolifcration of federal,<br />
state, and local regulations that restrict<br />
smoking in public places and work sites"<br />
is well founded . (]<br />
Ackno"iedgmeots<br />
This study wu supponcd in part by Nauonal<br />
Cancer Instirute eontracts NO1-CF7-1046-01<br />
and NO1-CP7-1096-Q? .<br />
The authors gratcfully acknowledge the<br />
assistance of numerous individuals and organizatioru<br />
who made this study possiblc . Sandi<br />
Ezrine, Patsy Henderson, Joan Huber, and<br />
other staff of Survey Research Associates, Inc,<br />
for valuable help in all phases of the srudy ; Dr .<br />
Jian Chang, Carlenc Anderson, Debbie Pinney,<br />
and Jcanu Shanebarger of the Missouri Cancer<br />
Rcgistry, NLssoun Dcpartment of Health, for<br />
assistance in data collection and patient tracking<br />
; Dr . Ellis Ingmam of the Urtivcrsin• of Mis-<br />
souri School of Medicine and Dr . Jeffrcy Mcycrs<br />
of the Atavo Clinic for their assistance in<br />
review-tng pathology shdes ; Drs . William Blot<br />
and Jay Lubin of the National Cancer Institutc<br />
for helpful comments on the manusenpr and<br />
the tvfissouri Department of Revenue and the<br />
Health Care Finance Administration for their<br />
help in selecting populatton-based eontrols<br />
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The rcliabairy of passive smoldng historics<br />
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1 S.ul Amencn )ournal of Puh6c Health A :o~-cmbcr 1992 . \'oI 82 . No . 11<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
Butler, T .L ., The Relationship of Passive Smoking to Various Health<br />
Outcomes Among Seventh-Day Adventists in California . Ph .D . Thesis,<br />
University of California, 1988 .<br />
Another U .S . study including workplace data is the 1988<br />
Ph .D . dissertation of Butler . This cohort study followed two<br />
groups of California Seventh-Day Adventists, members of a religious<br />
sect who adhere to certain lifestyle choices, e .g ., abstinence from<br />
smoking, caffeine and red meat . Despite the lifestyle differences<br />
suggested by membership in this sect, Butler's data have been<br />
included in discussions of workplace ETS <strong>exposure</strong> . For males,<br />
Butler reported a risk estimate of 1 .72 (95a CI 0 .33-9 .04) ; for<br />
females, the reported risk estimate was :L .47 (95% CI 0 .15-14 .06),<br />
for having worked with a smoker for eleven or more years . Neither<br />
was statistically significant . Despite the large number of<br />
individuals enrolled in the study, very few <strong>lung</strong> <strong>cancer</strong> cases were<br />
obtained . As a result, an extremely small sample size is a major<br />
flaw in this study .<br />
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tf1dNEFISTY OF CutFORtdw<br />
Las Anp&ls<br />
TM FtMatwnstvp ot Pass,va Smobnq to Vuious<br />
Haaltn Outcom.s unonq S.wrnh-day Adv.ntists tn Caliiorrua<br />
A tksi .rtaUon submrtted in parual satUstacUon<br />
of tt4 r .Qur .m .ms tor ttre daqreu<br />
Doctor of Publr. Healtli<br />
by<br />
T*nsnc . LssLa SWw<br />
1988
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TM dusarution ot Ttrr .nc . LtsJ,. Buti.r a approv.d.<br />
Sandv Grs.niuui<br />
Wilum SfwruCk<br />
Unricrsrty of CaJdortua, Los Angales<br />
1988<br />
Bubua V=nsr, Commatee Char
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A<br />
~ -1.._<br />
.`<br />
© CopynVM by<br />
Terrencs L*slr BuU.r<br />
1988
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Dadicat .d to the mwmory pf my moth .r<br />
Sarah Joan Burd .r11922•1987)<br />
A IHs of Immsa"abis qualnies<br />
ri
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Ust of Fquret<br />
list of Tahies<br />
TABLE OF CONTENTS<br />
Acknowi.dqements zw<br />
Vrta. Pubticanons and Prnsentanons za<br />
Absua a xx<br />
Ctupter I INTRODUCTION 1<br />
1 .1 Sadcground 1<br />
Paqe<br />
12 Researcti Hypott"as 3<br />
1 .3 SpecifiC Ob}rzctnws 4<br />
1 .4 Defrunons and Classtinnon nf T.rms 5<br />
1 .5 Sl9ruficance, Relevance and R.thonale 8<br />
1 .6 Orqancsnon of Thesa 9<br />
Chapter 2 UTERATURE REVIEW 11<br />
2.1 Introducnon 11<br />
2 .2 Companson of Mansiream and S+dsstream Smoke 13<br />
2 .3 Measurement of Passnre Sm>kan9 Ezpouxe 15<br />
2 .4 General HeaJth Ett®Cts 20<br />
2 .5 PtausibiYty of a Heatth Effect 22<br />
2 .6 Lung Cancer 23<br />
vw
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PaQe<br />
2 .7 Ott>.r Cancers 32<br />
2 .8 ti .art Dtsaase 36<br />
2.9 AJI Caus. Moriahty 40<br />
2.10 Summary 40<br />
Chapter 3 METHOOS 43<br />
3 .1 Bactcpround of Study 43<br />
3 .2 Study Destgn 52<br />
3.3 Dsscriptwn of tM Study Poputatwns 52<br />
3 .4 Data Dscnpuon 58<br />
3 .5 Outcortw Ascenanmant Procedures 61<br />
3 .6 Pass+ve SmoWn9 Exposura Assassment 65<br />
3 .7 Delntttons of Other Exposure Vanables 70<br />
3 .8 Data Anays+s and StatuticaJ Mslhods 76<br />
3 .9 Lirtrtahons and Potenuat Problems of Study 79<br />
Chapter 4 DESCRIPTIVE STATtSTfCS 81<br />
4 .1 Spouse Pars Demograpruc Data et<br />
4 .2 Smoknq Exposure 82<br />
4 .3 AHSMOG Cohoh Demographtc Data 90<br />
V
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Pa9e<br />
Ctupte . 5 LUNG CANCER RESULTS 97<br />
5 .1 Spouse Pars Cohort 97<br />
5 .2 AHSMOG Cohort 105<br />
5 .3 Summary 112<br />
Chapter 6 SMOFaNG RELATED CANCER RESULTS 114<br />
6 .1 Spous . Pars Cohort 114<br />
6 .2 AHSMOG Cohort 131<br />
6 .3 Summary 135<br />
Chapter 7 ALL INCIDENT CANCER RESULTS 140<br />
7 .1 Spouse Pa'rs Cohort Inddent Cancars 140<br />
7 .2 AHSMOG Cohort AJI Incident Cancars 145<br />
7 .3 Summary 149<br />
Chapler 8 MORTAUTY RESULTS 153<br />
8 .1 Spouse Pars Cohort - Ali Cause MonOty Resufts 153<br />
8 .2<br />
Spouse Pairs Coh«1- Iscrserris Herrt Disease<br />
Mortality Resutis 160<br />
8 .3 AHSMOG Cohort - A8 Cause MortaJity Resutts 163<br />
8 .4<br />
AHSMOG Cohort - Ischemie Haart Disease<br />
Mortality Resuns<br />
173
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Paqc<br />
e•5 SumerwY 176<br />
Chapt«' 9 DISCUSSlON AND CONCLUSIONS 180<br />
9 .1 Data Ouatity 18D<br />
92 Lung CancK t67<br />
9 .3 Smo+cmq R.lat.d Cancsn 191<br />
9.4 Csrwcal Canctr 194<br />
9 .5 All ~Cid.clt GuK1ri 196<br />
9 .6 Mortaltty Rautts 198<br />
9 .7 Condusans 199<br />
Rt/er .ncss 203<br />
Appan6oes 1 Gbssary of T4rmmotoqy and Abbr.matlorts 214<br />
2 AHS C.nsus Qu.stiomair. (1974) 216<br />
3 AHS lits" Qwstionrsalr . (1976) 226<br />
4 A1dSMOG Qwstionnair* (1977) 246<br />
5 AHSMOG Qu*svonnainl (1987) 254<br />
6 Drtta Cdleehon Fom1s 269<br />
1977 Nospitaf Hisiory Form . 270<br />
1883 Hoso+tal Hkstory Form 271<br />
bischarga Diaqrwsia Forrn 273<br />
Tumor Abstraet Form 275<br />
NI
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t15't OF AGUaES<br />
Fiynr• 3 .1 Row Criar1 of Advennst HMttti ShKly 47<br />
TabN 1 .1<br />
Paqa<br />
32 Firtabonstwp of Spous. Pars arxf AHSMOG Suo-<br />
Populatiorts to the AOvantist Health StuOy<br />
Incid.nc. Poputatwn ' 53<br />
tJST OF TABZF.S<br />
Smoiclnfl Fi .tatsd Canoars 7<br />
2 .1 D+stribunon of Consutu.nts in Manstraarn Smok•<br />
(MS) and >n. Rabo of Sioestnam Smoke (SS) to<br />
MS o/ non-fih.r ciqa»ttas 14<br />
2.2 Summary of Cas. Controi Studi.s of Lung Canc .r 25<br />
2 .3 Summary 0 Cohort StuCiss of Lung Cancor 31<br />
2 .4 Summary of Studas of Other Cancera 33<br />
2.5 Summary of Studi.s of H.an Dmeasa 37<br />
2.6 Summary of Studss of AJ Causa Mortality 41<br />
3.1 Aq .-Standarditrd Mortaiity fiatios @or SNretad<br />
Causes of Death Among 25 .000 Wfuto Calitoma<br />
AdvenCSts. 1 960-19L0 45<br />
3 .2<br />
8asa LUna Vutablss Msasut .d on ttw Thrs Sa1t-<br />
Admntst .md Owsbonnarea . 1974•1977 50<br />
3 .3 Spous . Pars Cohort : S .N .ct.d D.salptrv. Dan 55<br />
3 .4 AHSMOG Cohat: Ssl.et.d D.acriptn+. Data 57<br />
3 .5 Spous. Pairs Cohort : Spouse Smokrtg StatuY n<br />
Marnaqe 68<br />
vii
I<br />
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Tab1• 3 .6<br />
Paqe<br />
P .rcentaQ. Agresm.rit Batw..n two MtthoCs o1<br />
Class~ Husband's Smoknq Sunu in Marrap• 70<br />
4 .1 Spousa Pairs Cohort: Sax-SPscifiC Nsbibution of<br />
Aqe al LO by Ape Groups 01<br />
42 Spouse Pairs Cohort : Sex•Specific D+suibution ot<br />
Smokvp Siuus. 1976 82<br />
4 .3 SFOuxa Pairs Coftn : Sax•Sp.dflc ®+stn4uaon of<br />
MumCNr oi CiguMtts p49utvfy Smok" 83<br />
4 .4 Spov" Patrs Cohort: Sax-SptCtfiG Dismbubon of<br />
Nurnber of Yaars Fi .qutvty Srrwk.d 84<br />
4 .5 Spouse Pairs Cotsort Sax•Sptd6c Distritxnion of<br />
Pack Years o/ Cisar.ns Smoked 85<br />
4 .6 Spouse Pairs Cohort Smakxiq Status of Spouse<br />
Pairs 86<br />
4 .7 Spous• Pairs Cohort: Spouse Smokin9 Status in<br />
Marnaya<br />
4 .8 Spouse Pars Cohort : Ssx-SPscific Mortality,<br />
1976-1962 . by Unde(" Gausas a8<br />
4 .9 Spouse Pairs CoAon: Ses and S+t! SpaotliC<br />
InaderM Ca"s of Cane.r, 1977•1fl82 89<br />
4 .10 AhlSt./QG Cottiort: Srx-Spaeifio Distnbuaon of<br />
Age CwOups<br />
4 .11 AHSMOG Cohort Sax-Spstafic Datribuiion of<br />
&moiunq Status<br />
4 .12 AHSMOG Cohm Ssx•Spscific Octtnbuuon of<br />
Cigar .n .s Smoked<br />
4 .13 AHSMOG Cohort: Sex•Spacific Distribution of<br />
Ysars Smoked 92<br />
ix<br />
87<br />
90<br />
91<br />
91
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Paqe<br />
7aWe 4 .14 AHSMOG Conort : Sex•Sp+ahc DWjbubon ot<br />
Pack Years o4 Gparenes Srtwkod 92<br />
4 .15 AHSlAQG CctWrt : Sax-Splahc Daubutbn at<br />
Yean Lrved vrsth a Smokar 93<br />
4,16 AHSMOG Cohort 5ax-Sp .cftic prstribut,on ol<br />
Yeant Wark" wrCt a Smokrr 94<br />
4 .17 AHSMOG Cohort Sex~S~ec4fic Mortalrty . 1976-<br />
1982. by und.rty+nq Catq.s 95<br />
4 .18 A!-tSMOG Cohort Sax and Sjte Speclfic incttlsnt<br />
Gasrs ot Cancer . 1977-1982 »G<br />
5 .1 Spouse Pars Ftmatea : Histohgy d Lung Cancer<br />
Cases 98<br />
5.2 Spoaue Pairs Females : Ltnp Gancer, 1977-1982 .<br />
D+stnbution of ktadent Cases . Person Y.us, and<br />
Inc+dencA Rates by Age Grntp uKi Husbands<br />
Smokny Status n 1Aarnape 99<br />
5.3<br />
5 .4<br />
5 .5<br />
SPotus Pars F*rrtales : Age Adrusted Rate Ftat,os<br />
ol Lung Cancer . 1577-1>3E2, for Sekrcted Faeposiue<br />
Factcxs<br />
Spouse Pa+n Femaie Non-Smokers : Aqe Adfustad<br />
Rate Ratio Iw Linp Gancer, 1977-19M tor<br />
S.1s1.d Exposure Faators 1pA<br />
Spouse Ps+rs Fomate Non-Smokers : Cornpanson d<br />
Lung Cancer. Aqe AdEusisd Rat. Flatros IGr<br />
Exposure to Stwusa Srr+o~ usrnq Dinerent<br />
SI2USUCa1 mettWr*s<br />
5 .6 AHSMOG Cphort : HlstoloQy d Lunq Cancer C.zsss 106<br />
5 .7 AHSMOG Gurrent Non-Smokars : Lung Cancer,<br />
197'1-1982, DSstrrbuuon d Inpdent Cases, Person<br />
Years and Incdence Rates by Age Group ane<br />
Yeus l.rvW w+tn a Smoker 107<br />
a<br />
101<br />
105
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Tab1e 5 .!! AHSMOG C+xr`nt Non-Smokers : Lrxtq Cancer, Page<br />
1977-1982 . Ckstrbwon of ltvNdent Ca.ses . Person<br />
Years and tncrdence Rates by Age Group and<br />
Years Worked wrth a Smc+ker 108<br />
5 .9 ALHSMCY Fernales : Adjutted Rate Rntbos of Lung<br />
Cancer . 1977-19i32M for SMected Exposure Factors, 110<br />
5.10 AHSMOG Males : Ad}ust.d Rate Rat,oa of Lung<br />
Cancer, 1977-1982. For S.lected ExPosure Factors 11 t<br />
5 .11 AHSMOG Lung Cancer Adjusted Fiat . Rat,os for<br />
Varying Years and Types of PaSsive Smoking<br />
E, tsasur• 113<br />
6.1 Spouse Pars Females : Site Specific Distrtbtmon<br />
of Smoking Related Cancers 115<br />
62 Spouse Pairs Ferrules : Nt Smoking Related<br />
Ca .ncers, 1'd77-1982 . Distnbumon of irtoldent Cases,<br />
Person Years and Incidence Cases by Aqe Group<br />
and Husband's Smoking Status in Mamage 116<br />
6.3 Spouse Pars Females : Age Adjusted Rate Ratio<br />
of Srralang Retided Cancer Exdt6ng Lung Cancer<br />
tor Selectod Exposure Factors, 1977-19t32 117<br />
6 .4 Spouse Pairs F.rtules : Age A4{u:sted Rato Ratio<br />
of All Smoking R.tst .d Cancer lot SefeCted<br />
Expoux . Facior= 119<br />
6 .5<br />
6.b<br />
6 .7<br />
Spouse Pars Female NonSmokafs : Age Adjusted<br />
Rate Ratio of Smoking Related Csneer Exclfidmg<br />
Lung for Satected Exposure Facioes. 1977-1982 121<br />
Spouse Pars Female NonSmok .rs : Age Adjusted<br />
Rate Ratio 01 Smoking Related Cancer IndudNng<br />
Lung, 1977-1982 . for SNect.d Exposure Factors 122<br />
Spouse Pairs Frmale Non-Srtsokars: Smoking<br />
Related Cancers Ag. Adtusted Rate Ratios for<br />
Females Married to a Smoke{ or Mamed to a<br />
Non-Smoker 23<br />
n
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P aqe<br />
Tabte 6 .6 Spouse Palrs Females : twnrical Cancer, 1977-<br />
1982 . Diwibut,on of Irxad .rtt Cutas, Peruxt Years<br />
and Inadence P„^.tas Ly !qw Group artd Husband<br />
Smor
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Page<br />
TaGe 6.18 AHSMOG : Ai Srtwkinq R<br />
.tatad Cartcers Age Atttusted Rate Ratio for Vary»p Years and Types<br />
of Pass+ve Smokx+q Exposura 138<br />
7 .1 Spouse Pars Ferriales : Ap Incident Canwrs, 1977•<br />
1952, Drstrbuuon ot anoWnt .r.ases . Pe.ison Yeara<br />
and Inadence Ftates by Age Group and Husband<br />
Smokrnfl Status n Mamaqe ' 141<br />
7 .2 Spouse Pairs Fsmsles : Aqe Adjusted Ftate Ratio<br />
oi All inadertt Cancsr br SektieC Exposure<br />
Factors.1977-1982 143<br />
7 .3 Spouse Pars Non-Smokusq Females : Aqe Adiustsd<br />
Ftate Ratio of A!i hcidux Cancar, 1977-19E2, for<br />
Sebect.ci Exposure Factors 144<br />
7 .4 Spo+1se Pars Females : Adjusted Rate Fttmo ot All<br />
tncident Cancers, 1977-1982, for Selected<br />
Exposure Factors 146<br />
7.5 AHSMOG Current Non-Smokers : All Incedent<br />
Cancers, 1977-1982 . (hstnbubon of bncWent Cases,<br />
Person Years and Incidence Rates by Age Group<br />
and Years Lived wrth a Smokwr 147<br />
7.6 AHSMOG Curreni Non-Smokers : All h„rclent<br />
Cancers, 1977-1982 . pisiribuUon of dncdwu Cases .<br />
Person Years and Mxtidence Rates by Age Group<br />
and Years Worked w+th a Smoker 148<br />
7,7 AHSMOG Females : Adjusted Rate Ratio of AII<br />
Incident Cancers, 1977-1982, for Selected<br />
Exposure Factors 150<br />
7.8 AHSMtJG Males : Adjusted Rate Ratio of All<br />
Incident Cancers, 1977-1982, Ior Selected<br />
Exposure Factors 151<br />
8 .1 Spouse Pars Females : A11 Cause Mortainy,<br />
1977-1982, OLstnbut)on of peaths, Person Years<br />
and Inadenca Fiates by Aqe Group and Husband<br />
Smoknq Status n Mamaqe 154<br />
XIN
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Page<br />
Table 82 Spouse Pus Females : Age Adjutti.d F;a1a Ratio<br />
of AI Natural Cause AAortality, 1 fi76-1982, for<br />
Sel.cted Exposure Factors 156<br />
8 .3 Spouse Pars Non-Srralanfl Femalts : Age Adiusted<br />
Rate Ftat» of Ab Natural Caus . Alortaib, 1976-<br />
1982, br Selected Exposure Factors 158<br />
8 .4 Spouse Pa,rs Females : IsdMrrrc Hrart Ditease<br />
Mortality, 1976-1982, !)istribubon of Dsaths .<br />
Person Years and krcidenca f3ates by Age Group<br />
and Husband Smoknq Siatua in t4larnafle<br />
8_S Spouse Pan Non-Smokinq Fsmales : Age Adjusled<br />
Rate Rata of lsch.rnc Heart Dtsease t,Aortaity.<br />
1976-1982, for Selected Espmxe Factors 162<br />
8 .6 AHSMOG Curr .nt Non-Smotcers : All Cause<br />
Mortality . 1976-1982 . Distributicn ot Deaths .<br />
Person Y .ars and Incid .nca Rates by Age Group<br />
and Yaats llved wRtt a Srnacrr 16a<br />
6 .7<br />
AHSMOG Currant Non-Smokefs : All Cause<br />
Mortality, 1976-1982 . Dutributwrt of Deaths,<br />
Person Years and Incidenc• Rates by Age Group<br />
and Years Worked with a Smoker<br />
8 .8 AHSMOG FemaJes: Ag . A6)ust.d RaU Ratio of<br />
All Caus. t,Aortality, 1976-1982, /or Sebct.d<br />
E :poura Factors<br />
8 .9 AHSMOG Males : Age AdjuSfed Rate Ratio of All<br />
Cause Mortality, 1976-1982, for Selected<br />
Exposure Factors 169<br />
8 .10 AHSMOG Curr.nt Non-Smokars: tsChsrmc Heart<br />
Disease Mortahty, 1976-1982 . Distribution of<br />
Deaths. Person Years and Incadsno. Ratss by Age<br />
Group and Yeats Lived with a Smokef<br />
nv<br />
161<br />
165<br />
167<br />
171
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Paqe<br />
TaW.8 .11 AHSMOG taxrsm Non-Smok.rs : 6sctsarnic Heart<br />
Drsaast Morta4ty, 1976-19Q2, Distributwn of<br />
Dautu, Persort Years and incid .n>~. Rat®s by f.q.<br />
Group and Yraars Worked wrth a Smoker 172<br />
e .12 AHSM4G Females : Aqe Arijusted Rate Ratio of<br />
Isch .rric Haart Assaafe L$orsaliry, 1976-19lt2, tor ~<br />
SN.aad Exposure Fscoors<br />
e .13 AHSMOG Maltt : AQe AcffWRtd Rate Rauo of<br />
isctt.rrrc H .art Disaas. ftAarta[tty . 1976-1982, f r<br />
Se1ect.d Exposurs Factcrs<br />
9 .1 Spouse Pa/rs: Subjw Smokinq Status Perc .rtt<br />
Apr.am.nc Between 1978 artd 1967 Responses 182<br />
92 Spouse Pairs Females : Percent Aqr*.mant<br />
Batw*.n Cr.at .d Varnbl. 'Husband Smoked fn<br />
Marnaq.' and 1987 F4esaor4sa 'Lmd wRh Husband<br />
who SR1oked' 184<br />
9 .3 AHSMOG Cohort: Aqrsrt> .r1t Between 1977 and<br />
1987 Responses to ETS Expown Oueruons 166<br />
9 .4 A Compuison of R .4atiw Risks of Lung Cancer<br />
for ETS Ezposwe among tM AHSMOG anC Spouse<br />
Pars Cohorts<br />
9 .5 A Comparison of Retuiw Risks of A : Smokinq<br />
Fietat .d Cano .c toc ETS Esposur• among tt-*<br />
AHSMOG and Spouse Pars Cohorts i93<br />
9.6<br />
A Cornparison of R .latiw Risks oi All lncrder»<br />
Canc .fs fox ETS E:posure amonq the AHSMOG<br />
and Spouse Pars Cohor¢s<br />
9 .7 A Comparison of RNatiw Risks of As Cause<br />
Mortality lor ETS Expoetre amorty tt w AHSMOG<br />
and Spouse Pars Cohorts<br />
174<br />
177<br />
1a8<br />
197<br />
9 .8 A Comparison of Relative Risks of tschemrc HOsrt<br />
Drsaase for ETS Exp~osixe among tM AHSMOG<br />
and Spossa Pars Cohorts 202<br />
xv<br />
201
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CH/1FTHR 5: LUNG CANCER RESULTS<br />
In Uus chapter the results of ttk km9 <strong>cancer</strong> analyses are presented tor<br />
both the spouse pairs females and tM AHS/.1OG cohon. For the spouse<br />
pars femabs the hwtial analysas rtclude both the current and past<br />
smokers . Hovrever, later analyses are resuided to ;4 non-smolunfl<br />
poputation of th+s cohort. Akhouqh 0,4 major variables of interest afe<br />
the passrve smo" ezposures, other sefected factors are chosen for<br />
lndusan n the anatyses because triey may be irxlependent nsk factors<br />
or have some protective ettect on the outcome . TThe methods of<br />
analyses induded the calcuiation of a anude measure of ettect and<br />
stratdied anatyses .<br />
5.1 SPOUSE PAIRS COHORT<br />
In the ferrale population of tfle spouse pairs cohort nne incident Cases<br />
of pnmary king <strong>cancer</strong> were diagnosed duenp the toiow-up period 1977<br />
to 1982 . Histoto¢cal confirmation was obtarted for eactt case and the<br />
inforrnation abstracted from medical pamoloQy reports . The distnbuuon<br />
by histological type ts presented 'n Table 5 .1 . S+nce there were very<br />
few cases these were grouped together for analyncal purposes and no<br />
eNor1 was made to drfterenuate by vanous tustoloqicat types .<br />
97
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14Mobqcd TqVO<br />
t arp. cH urcx+o+rr<br />
ox ar qrv,arna<br />
TALILE LI<br />
Si'OUSE PARS • FEMALES<br />
iA3TOLD0Y OF 11LK1 (CMJ .'FA GAM<br />
Ap.roqrcmpm4 7<br />
A1I ths cases occurred in the age ranys of 45 to 69 and ony one of the<br />
rans cases was diagnosed n a former srnolcer . No cases occurred among<br />
females ctass,hsd as current smokers whiis eigM ca .ses were among nor-<br />
smokers . Table 5 .2 prtsants ths disatumon of inadent cases, person<br />
years and inadence rates by tsn ysar age Qroups sccordinq to ttw<br />
smoknq status o1 subject and spouse .<br />
A stratdied anaysrs, stratdynq on ten year aye groups . was pertormed<br />
and Mantet-HaenszN turnmary rate ratiGs and corresponc~ng 95! .<br />
conlidence ntervals were caka,fated 1or seiected <strong>exposure</strong> tactors . The<br />
inadence rates, crude rate rauos, age ad)usted rate rauos, confidence<br />
intervals and p-values are stwwn in Tabe 5 .3 . The ditterences between<br />
the crude rate ratios and adjusted rate ratios indcate that there was a<br />
98
c<br />
i.rVV !'S Ei'G(.ro(s<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
u<br />
d<br />
T ABt E 5.2 SPOUSE PArtS - tENtAt ES<br />
LUNG CANCER (1177•M02)<br />
Dt3TRJBU110N OF RiC/OEHT CASES. PERSON YEARS A1q MCIOEMCE 1'1/ITES NY AOE GROUP<br />
ANO Hl1S8AWD SMOKING STATUS 1N &tARfNA(DE<br />
A0 . ci-up<br />
MWKE _~~QtL''a110KEtt<br />
1K£ Si4OKF$__<br />
FRfSBAND SMOKER HU^o8AN0 NbPt SMOiKER IRt3fIM0? SMOKER II1tSBNW NOff SMOKER<br />
C.asss! RaW Cas.d RsN/ Cs.>tl ReW CassJ R»d<br />
P. ..on r.m 10.000 PY Prrson 1wo. 10.00o Pr Pw.on p.rr 10.000 PY P.r.oe fvan 10.00o Pr<br />
26-3R 0 9.2 000 0 800. 0 00 0 711 0.00 0 Mm 0.00<br />
3.5- .A 0 1652 0 00 0 1%37 0 00 0 t99 000 0•ti 000<br />
16-64 1 2190 4 .67 2 l520 2.10 01011 000 0 042 000<br />
6544 1 3000 3 .33 2 ®570 2.33 11240 9 .09 0 976 0 00<br />
65-71 1 2169 < .113 1 6900 1 .67 o' 02! 0 00 0 305 0 00<br />
75-01 0 602 0 00 0 2112 0 .00 0 70 025 0 39 0 00<br />
as 94 0 63 0.00 0 220 0 00 0 0 0 .00 0 L 000<br />
toul 3105)0 2/H 613052 1 .1s 1 46" 2.14 03610 0 00
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
contounding eftect by aqe tt7at to some extent was accounted ta n the<br />
stratdied analysis . The smal rxxnber ot cases and tow statabcal power,<br />
militate against the pouibiiity of achi .vuN stansticalty srgndicarn<br />
resuits . Pt is also mposs#Ne to sssass eftect mod'dication witt, so tew<br />
cases .<br />
For our ma(ar <strong>exposure</strong> tactor of irsterettt husband smokng status n<br />
marriage, summary rate raWs of 1 .94 (95% C .l. 0.46-824) and 2 .47 (B5• .<br />
C .I . 0 .29-21 .te) were obtanad for past and currenn <strong>exposure</strong> respectn+ely<br />
when compared to the refererd group o1 navef exposed . A smilar<br />
doubbng of the nsk was observed wnen the husband's smoking status<br />
was dichotomued nto never and ewr smoked, RR of 2.04 (95% C .I . 0 .5d-<br />
7 .55), No increased nsk of king ctnqr was observed in this popu(ation<br />
for the subiects own smokng sYariis . Fiowever, when smokers of more<br />
than ten pack yeus oi caga»tte amok»g were tanpared to the referertt<br />
group 04 non-smokers iTere was increased risk obserued, RR of 2 .22 (95%<br />
C .I . 028-17 .74) . The sofitary case n ttN ecposed category ikustrates<br />
the equivocal nature Ot these resutlf .<br />
There is a suggestion of a decreased risk for those subtects who have<br />
anended college versus ttwse with a high school educaUon or less and<br />
an increased risk tor subtects with blue colar work,ng spouses compared<br />
100
0<br />
TAIILE 5.3 SPOUSE PAdAS • FENWII E5<br />
AGE ADJlJ3iED RATE RASIQS Vltl) OF 111F43 CJVICER 41177-11t2)<br />
fOR 3ELECIEO EJO*OSUIIE FACTORS<br />
f.ct« L .,.ds ' Cs.'J • Vad (', .ud. Ad}est.d<br />
Pr.on Y.r. 10 i'V N(1 /1R- 06% C.1 .)<br />
1 hesbrd SmoM.+O F/ .v.r 6 A7270 106 ft .l. Rd<br />
s1aR» n Prsi J 11564 259 2 44 1 .94 (0 46-92J1<br />
mareu{7• Curnrd 1 3912 256 2.41 2.47 10 2931 _ 1 ./ p -0 69<br />
l lusband smok.d No 6 4727. 106 Rd. Rd .<br />
It, r„~„vq. Vs 4 15560 257 2.4J 2 0o t0 .61-7 .651 P' 0 27<br />
F .mat" rrio4irq Nw.r 0 54091 146 Rs/. Rsl.<br />
stalut P.sl 1 755! 132 091 0/18 10.11,{92/ p•0/l4<br />
Curnni 0 8e4 0 0.00 0 00<br />
F:meh 9.eo4od Non-sa+mU.r •54i91 146 RN. Rsl.<br />
Smowr 1 8443 lii 001 0.i0 (0.10-1 .3i1 p∎0.03<br />
Pack y..rs d Noa+. 156772 14/ Rd. ArtU<br />
t.nokin0 Mnuf. 0-10 0 3534 0 0 00 0 00<br />
> 10 1 2e27 354 2 51 2 22 (020-17.741 p .0 5S<br />
EducaNM lkqh 9cAod 421036 100 Rd. f;s[.<br />
CoMOqr • 4 4J26] 116 061 0 75 (0.20-2 1131 p- 0 64<br />
Liw in nr.i v.s 330201 99 Fl.l. R./<br />
~'~j ~iy roa No 632490 154 1 55 1 .59 (0 J6 6 65/ p• 0 SJ<br />
~-ii~ Y~_,-.lV~~r~'ylll.r<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
a
d<br />
9V YTSr 0S ryv 0z<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
T/IEILE 5.3 cawnm.d<br />
f actor Lr.l. ' Cassd<br />
P.roa, v.w tO P1r<br />
Cends<br />
Ra<br />
A4rsW<br />
r1R- hs% C.l)<br />
Syous. Wha. Caaar 234665 66 R.1 R.1_<br />
Oocup- Beu. Cosar 626120 230 3.96 4.16 t0 .78-22 .161 P' 0 10<br />
feuA kds. 11 - tras w.a 126169 153 R.f_ Nl .<br />
•-10 lrnst w"k 423951 167 1 .0! 1 .22 10 31-4 101<br />
0-3 Mm.s w.w 1 12005 N 0.6f O.N IM0)-6 .011 p1 0 67<br />
R.u-Cardwr NqA 422104 171 Rs/ . Rs1.<br />
bn0. 9406wm .19a.2 201 1 .12 1 .23 (0.31- . .1/21<br />
0 lo,. 1,21317 47 0.26 0.31 p.03-2 .92/ P"0 .46<br />
' pesa.prncol M casss snd pnson yws Ms dw b<br />
mrarq v.lust n s.pos.rs Isdat ToUf 'ub,.eb - 11 .060<br />
• RsN p.« I nrwon pwson rws lunp Canc.r Csss -9<br />
~ µamN Ns.nst.l summ.ry uN nNO PRR/ - s6p+st+d ia "0 7otd 0'caam tloce - H.407<br />
Rd. R.1«aA prOnp
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
to subt.cti with wtwt, cotlar woricir>q apousas . Mowever, bcth rasutts<br />
ara subfect to biss because d thw unwwwn csassificat,on of one of tt,e<br />
cases and ttts rttissrV nurnber d p .rson years .<br />
Since tttere was only otte case among tf» 1 .475 ftma}.s who had ever<br />
smoked, k was d#fiauti to assass the lntk*nc* of active smoldng on t1x<br />
overall .#tact of ETS sgxosurra. Th .refon hxtt>.r stratified artiatyses<br />
w.re restncted to ttK 9 .370 never anokinq Iemalss . The results oa<br />
these analys.s ar. presant .d n Table 5 .4 . Somewhat similar resutts are<br />
otuerved as n ihe prwbus analysis and t'he same caveats conceminq<br />
ettect rnodihcauon, bias and sutistrcat sipniflcance aApiy. For the<br />
vanable husband smoked in rnaniaqe, the aqe-adNsted rate ratio was<br />
2 .02 (95'i. C .I. p .48-8 .56) .<br />
An additanal analysis usnq tfK conditional maximum EkeGhood mmator<br />
and an exact method tor spars~ data was pertormed and the nasid! a<br />
compared with the Mantel-Maeruzei estimates in Table 5 .5 . Tnese re"s<br />
have sirrulat pont lstmatas with tM mid probab+ttty exaCt bnornal<br />
confidence intervals beinp somewhat w+du and more conservative .<br />
103
NVV L .-7 ® . .'T C.i llZ<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
TAdLE 5 .4<br />
SPOl7SE PPi1S - FEM1L .E WON-S/iOaEAS<br />
A[1E AD.R7STED RA)E R/17109 (f" FOR U1N0 CJIF7CER ftf77•1M2y<br />
FOR SELECIED E7fPOSURE FACiOFt9<br />
Factar L.../a ' C1's. ./<br />
P.rson Y.us<br />
• 1}aw<br />
~ PY<br />
Crwd.<br />
RR<br />
Ae~shd<br />
RR- "b76 C.LI<br />
IbsWrd$mofaYtO N~oN 6430?7 11t Rof. Rd.<br />
status o P .st 2 i090 247 2 13 1 s! 10.32-t.pl<br />
n.una" CwI .nl 1 2466 102 341 337 t0 .3f/-21.051 p-Q M<br />
Misb .nd « No 6 43007 I ti RM. 71d.<br />
b wurr..p . Y.s 310576 2!4 2.45 202 10 N-6 661 p-0.32<br />
Edustics IfipN 3cMd 316063 te7 Rd. FM/ .<br />
g CoMO. • 631670 129 069 0.06 p0.20-3 971 p• 0.02<br />
Lkv fn nsrai Ys 3 26013 115 R.i . Rd .<br />
o.. No 427694 144 1 .26 1 .30 (0 .21-6 H 1 p . 0.73<br />
9ponta WtrN tollar 231217 E4 FFaI . RAI1 .<br />
pccup- BOw co4r 420768 269 4 .61 4.19 10 f0-2t.71) p .0 06<br />
g®b Carelur F40A 410454 206 PAL RN .<br />
Y1dos RMOcun 311065 176 0 65 093 (0.21-4 .17)<br />
Low 117660 67 027 033 (004•211% p-05!<br />
Dsci .pwKrs n c .s.s and pKton y.rs re Guw to<br />
~•a+q .rua n•.posw• Lctoes Tdal S„bpcts - f .370<br />
/1n* pw I nwwn pwsm y.ais LunO Gi+cw Casos -•<br />
Mam .i iu.nuN summary caas roo 1OR1 • .dlusNd ta ag. To1al P.rsa+ Y.ars - 54 $98<br />
Rd tht.r.M piwp
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
TAN .E a .f<br />
Si'OtlSE rAitS - FfA4ALE MOii-S00WRS<br />
A COtiPARI*aL1N OF Llt*lp GMCEfi AliE ADA1STM iNTE MTIOS<br />
FOP D0'OSUFlE TO 3pOIJSE aM010rKi lR3t+lli<br />
OFF9*NT $TATISTICJI . METt'100S<br />
FACTOR tFYELS • sETFK10<br />
LC,JUSTED<br />
M 05'Y. C.L)<br />
F4,abard fmdied No i'4=7 MMU6144"nusi RM .<br />
n Marnaq. r .. 11051s 2.02 ro .•a.a.lAi<br />
rb µanTom, t .&Gi+,ooe a.r .<br />
Ys 201 )0.9l-L7s1'<br />
• taaa DKSOn yrars<br />
^od MObWh Ir,A .ev»n/ enomrl CW1FK%nrc+ MW rv.i•<br />
5.2 AF-tSiA 0G C'.O FiORT<br />
purr>9 the yeus 1977-1982 tttuteen incidertt casaa o/ kng <strong>cancer</strong> w.re<br />
diaqnosed in th4 ourrarn non-smoke«s a the Ai-tSMOG cohort Seven or<br />
the cases were maMs and six w .re Lmsla . ThA hictobqicsl types ot<br />
tumors are presented in Tabl . 5.6. As witft tne spouse pairs cohort the<br />
most predortrnant histoloQieal type was adonocareinama. However, all<br />
Ptisto)oqical types wera grouped to9etfxK tor anYyUCnI purposas .<br />
105
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TABLE 5.6<br />
NMSMOG<br />
HlSTOLOGY OF LUNG CANCER CASES<br />
Mestoioqicai Type Idai. F.male<br />
Large al carcinoma 1<br />
Circnortsa NOS 1 1<br />
&quamous ca1 carcinoma t<br />
Adenocarcinoma 4 4<br />
Unknown 1<br />
For females, cases occurred in the age range of 55 to 94 years while for<br />
maes, cases were fimqed to t?» 55-84 yaar aqe range . The disvifwtton<br />
of ncident cases, person yeafs and incidence rates by ten year ape<br />
groups for the two ETS <strong>exposure</strong>s o( antereat-years frved with a smoker<br />
and years worked with a smoker--are presanted in Tables 5 .7 and 5 .8<br />
respectrvely . There is an ncreaserd risk for age, however, the lacsc ot<br />
sufticaent cases prevent a carefui assessment of trend across passNe<br />
smokinq <strong>exposure</strong>s .<br />
106
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TA[1LE 5.7 A1kc.rf.UXl - CURREMT NOM-SIAOItER3<br />
tuFx) CANCER 4»77-1sW)<br />
D191RIOl1TqN OF iNC1QCMT (',1lSfs . PERSON 1IEJIf1$ JtPdO WClDEFICE RATES ®Y A(1E (DFFOUP<br />
M1D YEARS LIVED NFlR1 A SA/OttER<br />
FEIMLE<br />
A0. 0ra+'<br />
Cas.fl<br />
Pason y..n<br />
YEAFR9 LIVED MNTl1 SMOKER<br />
NDM 1-10 YEMR I I • yFpJL1<br />
Rwl<br />
10.000 PY<br />
Caa.sl<br />
Prrson y.rs<br />
tirW<br />
1D.000 PY<br />
Cas.y Fl.1N<br />
Pr.on y.rs 10,000 PY<br />
26-31 0 $36 0 00 0 243 0 00 0 3" 0 .00<br />
35-44 0 1671 0 00 0 420 0 00 01149 0 00<br />
0<br />
J<br />
45 64<br />
6594<br />
0 2617<br />
0 329Y<br />
0 00<br />
0 00<br />
0 947<br />
0• 072<br />
0 00<br />
0 00<br />
016219<br />
17?6!<br />
0 00<br />
4.41<br />
i6-74 1' 2687 3.72 0 677 000 11791 6.6e<br />
75-04 1 139! 7.16 0' 254 000 o m 0.00<br />
25.54 1 340 29.41 0' H 000 1 169 92.02<br />
Total 112647 2.37 0J202 0 .00 10171 3.9?<br />
MSLE<br />
Aq. (kow<br />
26-31 0 382 000 0 102 0 00 0 142 0 00<br />
3544 0 960 0 00 0 264 0.00 0 379 0 00<br />
4554 a 2109 000 0 495 000 0 77! 000<br />
5564 2 2371 8 _44 0 403 000 0 fS5 000<br />
65-74 0 1683 0 00 0 311 0 00 2 596 3359<br />
75 64 3 •70 34-17 0 il 0 00 0 204 0 oo<br />
8594 0 212 0 00 0 s 0 .00 0 11 0 00<br />
laa/ 8 a61s 6~0 01724 000 23107 s44
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
9 s 4888288 :•<br />
oooOeoo .i<br />
I<br />
I<br />
fi =ow p -<br />
10 ~ N<br />
OOOa%-Oa -<br />
888 t 888 ,It<br />
00004000 -<br />
000 :.000 -<br />
88888-8 Si<br />
O00OI4111g W<br />
i<br />
O O O O--N •<br />
8888888 8<br />
O O O O O O O O<br />
h<br />
eooeo00 0<br />
9888988 s<br />
O O O O OAO .<br />
~<br />
b O O O O N O N<br />
9889328 A<br />
ooo .^ - O .<br />
i<br />
O O O N N -O q<br />
Tf = T S W S mi 7 W V n mmiz S g<br />
a<br />
~~ RAM" ..<br />
ioe
l<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Th .re w.re no casas ot " canc.r for *Vw saa an u» subjects who<br />
had liv .d for 1 .10 yean with a arTwka}r . For males tRere were no cases<br />
among ttiosa who had workad eleven years or more with a smoker .<br />
Four of the tfvrieen cases ocourred among form .r smokers aM of whom<br />
smoked more uan 9an pack years of cs9ar .des . In a s»afied analysu .<br />
adjusting for aqe and aex. 1lye rate ratio of " <strong>cancer</strong> among those<br />
amoknq more tfun trn pack yaars compared to tllosa who wae non-<br />
smoke+t was 2s1 (95`h C .f . 0.T8-1020, p-0 .0fs). Cons.vwntly, past acavvs<br />
smoknq .xposwe was tr.al .d as a ooMeurx3er and contralNd for by<br />
suatdication in addRional artafysls.<br />
The results of stratified anaryses for sefected expostue factors<br />
controlRr.q for age and sutaocts past srnokin9 status ar* presented 'en<br />
Tabre 5 .9 for fernales and Table 8 .10 fer males. The diNerances in the<br />
cnrde RR and adjusted RR wxficate sortw confounding due to past actrve<br />
smokinq arKVor age difl.rences n tM popufation and therefors tr~e<br />
adjusted summary rate ratios are considered as unconfounded by tne<br />
subjects pazt smoking status or aqe . For females who had Iived eleven<br />
or more years with a smoker as compared to females who had newr<br />
tived with a smoker the rate ratio of (unq <strong>cancer</strong> was 1 .16 (95y C.t.<br />
0 .20.6 .61) . For temahs v.tw Rad worked eWven or rror• years vntth a<br />
smoker the correspondinp nte ratio was 1 .47 (95', : C .1 . 0 1 5- 1 A 06),<br />
109
VsV 6soG CsoZ<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
T11[f1.E 5.9<br />
F .c1a iwdt ' Castsl<br />
Ptrsort Y.rt<br />
/Y13M0(3 - FE/MLES<br />
AO.A/3TEO RAIE FiAil03 .(F1FZ1 OF IIXJO GUVCEfl /ttT7-111t?)<br />
FUR 9ELECTEO E]0'OSl1FZE FACIORS<br />
JaW<br />
10 F'Y<br />
Cnd.<br />
Fni<br />
Adpsltd<br />
fvl- 05% C-i. )<br />
Ywws Uvod Norr 3 12ttt 23s RN. q.l.<br />
.Nh Snak.r 1-10 ywt 0 3301 0 0 00 0 00<br />
11 • lr.rs 34213 365 1 .56 1.16 (0.N1-661k p•0.a<br />
Ywrs YVoa1ad Non. 413161 299 RN. RsF.<br />
.rAo $rtnlow 1-10 ys.t 1- 6602 172 060 103 /0.11-10.11)<br />
-11 • "art 14670 214 0.7s 1 .47 (0.15-11 .06) 0•0.11t<br />
o lbut d 0-160 1 0273 16! FtN . FIM.<br />
®widw 161-3000 013421 2" 1 .t7 1 .7, t0 .20-1625)<br />
> 10 ppiw > 3000 1 0[3S 216 1 .36 0.90 10.05-16 .t3) p- 0.t0<br />
tburs d 0-100 1• 632t 1q RM. FiN .<br />
TSP 101-7000 .•190'7t 907 1 .63 1 .25 (0.14-11 .2M<br />
> 200 ppw > 3000 1t Sl66 168 0.n 0.69 (OVi-s.t1) y•i-a<br />
Eductpiaft mu.'s seteem 3 9213 326 W/. pd.<br />
CqMqt • 3 1496/ 200 0.61 1 .22 (0-2f-8.231 V o 062<br />
Ba/a-Carotwi. FiOA 2 t590 m F1N- RtF .<br />
Ind" FhdM" 3 7197 417 . 1 .71 111 (0w-t0 .ts1<br />
Low / 02" 121 0 62 035 M 07-4Jtl 0-01/<br />
DtscsopMUNS n csSSS arM pNlsOn YlMt re dUe 10<br />
nnsw+q afus n sposur . /saor. Tald 3uANcH - 4 .024<br />
• Raeft p.. I m+on p.. .on pwt Cancr Cass - 6<br />
- }AuMtl 14wn.1 surwrnarY mtt wbo (fMII-t4 /m aqt i smokr+0 stsAvs Tola/ Psrson Yws - 2t .100
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
3AULE 5.10 JWtsMoo - wIAt.Es<br />
AI7AISiET) F6iTE TTAiIOS (1tli) OF LUPI(I CANCER {1677-10rt2}<br />
F .ctor L.vsb ' Cos"<br />
Paaon Ysrs<br />
FOA SELECTED E)fPQSi1RE FACTORS<br />
• F~td<br />
10 PY<br />
Cnd~<br />
FiR<br />
la~usMd<br />
F1R" (ti6X C.C)<br />
Yoms Lov .A Non. 6V723 673 Fi .Q . R.f .<br />
wAr Snde.e /-10 years 01729 0 000 0.00<br />
it . 1 .ars 21123 640 1 .12 1 .i7 (0 .21-b.{1) P∎064<br />
Y.rs WrJrt .d Mon. 517m 625 p .t. R.t .<br />
.MU, 8woko. -1-10 Yamrs 23159 633 1 .01 1 .72 (0 .3 T-0.01) P- 0.3lS<br />
11 . y .ars 034.10 0 000 0.00<br />
Ftmws d 0-160 0 3S0!<br />
Oririnl 1e1-3000 47429<br />
> /0 Ww > 3000 32942<br />
ltaxs ml 0-100 !S3M<br />
1SP 101-3000 3EOS4<br />
> 200 Ppm > 30m • M/•<br />
Edacatian NiQY+ 8chool 3 3221 705 Tt'sf . Fisl.<br />
CoM.p. • 39692 310 a3T1 O.i6 /0.i7-3 .77) P-0.02<br />
BolaGrgWrw F1-gA 14114 243 SiYt . ROi.<br />
Ind+r Med:um 3101* 746 3 07 .1.61 (0 l1-9$16)<br />
Low 25302 377 t .55 1 .116 (0.ti-21 .73) p-0 .23<br />
DiStrlpanC.N n ta"s Wd DMfd7 yMmvt aee l1ue lkx<br />
mnsng vaiwt n .rpaturs l .c6i.e laUt Sub»cts - 2 .261<br />
. Rm per I aciron p.rson yeart Cw+c .r Caset - 7<br />
- AAx*c1 FRs .nSloi tunwnuy 1lt. iaao iRR)-&q ta eyes t sr.rokws0 tiafui 7,ta1 P~wsan fiurs - 13.A55
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Srmlar resutts are obs.rvsd n Table 5 .10 for t:he male cohort . There cs<br />
a slight ncreased nsk for subjects who lived eiew,n or rtwre years wrth<br />
tl srnoker as compared to thase wtto had not hvtd with a srrwker,<br />
RR R 1 .17 (0 .21-6 .81) . For ETS •xposur• at work the raie ratio of <strong>lung</strong><br />
c,ancer rn males is 1 .72 (95% C .l . 0.33-sa .0d) . Since we tuv .' vcry few<br />
cases the concht,ortat maximum tkefihood RR estimate and the exact rn+d<br />
probabltity brnorrwal confdence ntervais were also calcuLated and the<br />
rsutts are detaied in Table 5 .11 . TTwse resutta aue simiiu to the<br />
0.1atuf•Haertazei stsatifi.d anstysis .<br />
5.3 SUMMARY<br />
In both populations anah/zed tfWe appears to be a positrve eftect Of<br />
passrre smoking <strong>exposure</strong> with the outcome of <strong>lung</strong> <strong>cancer</strong> . Each of the<br />
adjusted measures of eftect for aD the ETS variabMas atxyw a positrve<br />
effect for expowe . However, the maQrviude of thatt effect vanes<br />
dependng on the cohort observed and the pyrticutar <strong>exposure</strong> vartable<br />
used . For both sexes n the AHSMOG cohon the reaults indicate ttut<br />
workng with a smoker has a gruter Nisd on " <strong>cancer</strong> than living<br />
wnh a smoker . However, the resulis shouJd be wuerpreled cautiously<br />
because of the small number oi casss that occurred n both populations .<br />
Further dacussion of the resutts ue prasented tr : t1ie finaf chapter .<br />
112
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
TAaIIE f.tt<br />
MiS4Ot] • UAJCi CJJ1CEFl<br />
` AD,It131® RATE RATIA3 FOR VAJiY1NCi YEARS<br />
Jm TYPES OF rA33tNE f11fM10 DO•OSt1RE<br />
rammw an+oM F.n>tM"<br />
E,pos,r• C.saPl RR ,'llOx On"<br />
Ysw tiwd<br />
sh SrMOrar<br />
td"<br />
Crm+PY RR MSx C)•°'<br />
/ioni 3'i'sltl<br />
0 030,<br />
AM .<br />
a00<br />
Llna<br />
a'1 T24<br />
aa<br />
0000<br />
„ • 1 7219 , .22 10-W .lil<br />
o•0 .a<br />
U1YJ 1 .1t (0 154 74)<br />
p•au<br />
Yan Wrated<br />
.iW Smok.r<br />
No" 4,3161 fiM . L7*6 Rrl<br />
,•t0 1 SA02 t .0t Va04•9.091 21151 1 .68 (0 .72-L11)<br />
„ . , 4670 , .34 (0 05-126b) 02420 0 .00<br />
o-0.7s<br />
v-o3S<br />
• Cmowrw mazarusn 6t .wuroa arm.fa aa aA .qua,.a r« ps n.o pass<br />
Wr+ok ..fl ass,•<br />
AAa vrowwry (M .w,«,) e .uoen.+ cc.,Fd.C,cs ".wW<br />
113
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3
Fontham, E .T .H ., Correa, P ., Wu--Williams, A ., Reynolds, P .,<br />
Greenberg, R .S ., Buffler, P .A ., Chen, V .W ., Boyd, P ., Alterman, T .,<br />
Austin, D .F ., Liff, J ., and Greenberg, S .D ., "Lung Cancer in<br />
Nonsmoking Women : A Multicenter Case-Control Study," Cancer<br />
Epidemiolocry, Biomarkers & Prevention 1 : 35-43, 1991 .<br />
Fontham, E .T .H ., Correa, P ., Reynolds, P ., Wu-Williams, A .,<br />
Buffler, P .A ., Greenberg, R .S ., Chen, V .W ., Alterman, T ., Boyd, P .,<br />
Austin, D .F ., and Liff, J ., "Environmental <strong>Tobacco</strong> Smoke and Lung<br />
Cancer in Nonsmoking Women : A Multicenter Study," Journal of the<br />
American Medical Association 271 : 1752-1759, 1994 .<br />
Another American study was first published in 1991 by<br />
Fontham and colleagues, as a preliminary report on a case-control<br />
study of women in five U .S . cities . For all <strong>lung</strong> <strong>cancer</strong> cell types<br />
combined, an odds ratio of 1 . 34 (95% CI 1 . 03-1 .73) was reported for<br />
those women who reported that they were ever exposed to ETS in an<br />
occupationall setting . Fontham and colleagues (1994) recently<br />
published a report on all five years of the study . They present a<br />
"crude" riskk estimate for workplace <strong>exposure</strong> of 1 .12 (955~ CI 0 .91-<br />
1 .36), which changes dramatically after adjustment for a number of<br />
variables to 1 .39 (95% CI 1 .11-1 .74) . The magnitude of the change<br />
following adjustment is much more pronounced for the workplace risk<br />
estimate than for the other risk estimates in the paper . Moreover,<br />
the upward increase after adjustment_is suspicious . Fontham and<br />
colleagues do not address this apparent discrepancy .<br />
al . ., 1994 report :<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Additional criticisms may be made about the Fontham, et
• Despite the study's use of cotinine to assess current tobacco<br />
use, the authors acknowledge that misclassification of ever<br />
smokers as lifetime never smokers is "problematic" because<br />
there is "no biomarker of lifetime tobacco use ." Moreover,<br />
only slightly more than half (54%) of cases had cotinine<br />
determinations . Thus, not even recent active smoking was<br />
excluded for nearly half of the cases .<br />
• While the authors stress that their study is a multicenter<br />
case-control study, if the characteristics of the study<br />
population are examined, it is seen that the vast majority of<br />
cases and controls come from two areas in California (Los<br />
Angeles and the San Francisco Bay area) . Yet, the authors do<br />
not indicate that air pollution, which has been suggested to<br />
be a <strong>lung</strong> <strong>cancer</strong> risk factor, was "adjusted" for in their<br />
analyses . In fact, the authors provide no breakdown of the<br />
data by study center, and it is not possible to ascertain<br />
whether the reported risks were consistent across the centers .<br />
Heterogeneity in the data among study sites would argue<br />
against combining the data as was done in this paper .<br />
• Among other potential confounders that were not considered in N<br />
0<br />
the analyses is dietary saturated fat intake, recently N<br />
~<br />
reported by Alavanja, et al ., to be associated with relative ~<br />
Ll<br />
risks as high as 6 .0 to 11 .0 . The risk was highest in ¢,<br />
r1~h<br />
nonsmoking women with adenocarcinoma ; over 75% of the cases in n<br />
0<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
the Fontham, et al ., study were adenocarcinomas . Alcohol<br />
consumption, another potential confounder, was also not<br />
mentioned . Recent studies have reported that smokers, and the<br />
persons living in their households, are likely to consume more<br />
fatty foods and more alcohol .<br />
• The presentation in the Fontham, et al ., study does not<br />
provide data for the possible associations between diet and<br />
other potential confounders and <strong>lung</strong> <strong>cancer</strong> . It is thus<br />
impossible to judge whether fruit and vegetable consumption<br />
was associated with <strong>lung</strong> <strong>cancer</strong> risk but not with smoking<br />
status, or with smoking status but not with <strong>lung</strong> <strong>cancer</strong> risk .<br />
The reader must take the authors' position that the factors<br />
were not confounders at face value, without the opportunity to<br />
examine the data .<br />
• The "adjustment" of the reported risk estimates is difficult<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
to interpret, as the adjustments take into account both study<br />
design variables (e .g ., subject age) and potential<br />
confounders . It is not possible to determine what might be<br />
affecting the adjustment . In particular, the dramatic upward<br />
shift (1 .12 to 1 .39) in the risk estimate for workplace ~~<br />
~<br />
<strong>exposure</strong> is puzzling and surprising . The shift is opposite N<br />
~<br />
the direction expected, and is of a magnitude unlike the other ~<br />
~<br />
adjustments in the paper. ~<br />
~<br />
M'i'
• The study population characteristics also reveal that over 70%<br />
of cases and controls were aged 60 or older . This calls into<br />
question the accuracy of childhood <strong>exposure</strong> estimates provided<br />
by these women, who were asked to recall parental smoking<br />
habits of more than 50 years ago ._<br />
• Furthermore, the socioeconomic and educational composition of<br />
the study population argues against generalizing results<br />
reported from this study to the United States population as a<br />
whole . The majority of cases and controls were drawn from low<br />
socioeconomic strata : more than 40%- had household incomes of<br />
less than $20,000 . In terms of education, one-third of cases<br />
had no more than a high school education .<br />
• The conclusion stated in the abstract of the paper -<br />
"Exposure to ETS during adult life increases risk of <strong>lung</strong><br />
<strong>cancer</strong> in lifetime nonsmokers" -- gives the appearance that<br />
the reported results are applicable to both men and women,<br />
when in fact, only women were studied .<br />
• Fontham and colleagues neglect to discuss the available<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
workplace data from other spousal smoking studies . Of<br />
particular interest is the notee that several large recent<br />
case-control studies (Janerich, et al . ; Bro4mson, et al . ;<br />
Stockwell, et al . ; Wu-Williams, et al .) have reported results<br />
for workplace <strong>exposure</strong> that were not statistically
*-qaIVI---I<br />
significant . Fontham, et al ., should have put their data in<br />
context .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
1<br />
Environmental <strong>Tobacco</strong> Smoke and<br />
Lung Cancer in Nonsmoking Women<br />
A Multicenter Study<br />
El zabeth T . H Fontham, DrPH, Pelayo Correa, MD ; Peggy Reynolds, PhD ; Anna Wu-Williams, PhD,<br />
Patricia A Buffler, PhD, Raymond S Greenberg, MD, PhD, Vivien W Chen, PhD, Toni Alterman, PhD,<br />
Peggy Boyd, PhD . Donald F Aust n, MD, Jonathan Liff, PhD<br />
(3toctiv. .-To determine the relative risk (RR) of <strong>lung</strong> <strong>cancer</strong> in lifetime never<br />
smokers associated wit environmental tobacco smoke (ETS) <strong>exposure</strong> .<br />
Design,--tviutticenter population-based case-control study .<br />
Setting .--Five metropolitan areas in the United States : Atianta, Ga, Houston,<br />
Tex, Los Angeles, Calif, New Orleans, La, and the San Francisco Bay Area, CalK .<br />
Patients or UtMr Pa rtlclpants .-Female lifetime never smokers : 653 cases<br />
with histologicalty confirmed <strong>lung</strong> <strong>cancer</strong> and 1253 controls selected by random digit<br />
dialing and random sampling from the Health Care Financing Administration files<br />
for women aged 65 years and older .<br />
Main Chltcome M .asur. -The RR of <strong>lung</strong> <strong>cancer</strong>, estimated by adjusted odds<br />
ratio (OR) with 95% confidence interval (Cl), associated with ETS <strong>exposure</strong> .<br />
Resutts -<strong>Tobacco</strong> use by spouse(s) was associated with a 30% excess risk of<br />
<strong>lung</strong> <strong>cancer</strong>. all types of primary <strong>lung</strong> carcinorrla (adjusted OR=1 .29 ; P< .05), pulmonary<br />
adenocarrinoma (adjusted OR=128 ; P< .05), and other primary carcinomas<br />
of the <strong>lung</strong> (adjusted OR=1 .37 ; f~ .18) . An increasing RR of tung <strong>cancer</strong> was<br />
observed with increasing pack-years of spousal ETS <strong>exposure</strong> (trend P= .03), such<br />
that an W16 excess risk of <strong>lung</strong> <strong>cancer</strong> was observed for subjects wftt180 or more<br />
pack-years of <strong>exposure</strong> from a spouse (adjusted OR=1 .79 ; 95% CI=0,99 to 325) .<br />
The excess risk of <strong>lung</strong> <strong>cancer</strong> among women ever exposed to ETS during adult<br />
life in the household was 24% ; in the workplace, 39% ; and in social settings, 50"k .<br />
When these sources were considered joint)y, an increasing risk of <strong>lung</strong> <strong>cancer</strong> with<br />
increasing duration of <strong>exposure</strong> was otuerved (trend I= .001) . At the highest level<br />
of <strong>exposure</strong>, there was a 75% increased risk. No significant association was found<br />
between <strong>exposure</strong> during childhood to househoki ETS <strong>exposure</strong> from mother, father,<br />
or other household members ; however, women who were exposed during<br />
childhood had higher RRs associated with adult•Ilfe ETS <strong>exposure</strong>s rilan women<br />
with no cNldhood <strong>exposure</strong> . At the highest level of adult smoke-years of <strong>exposure</strong>,<br />
the ORs for women with and without chikihood <strong>exposure</strong>s were 3 .25 (95% CI, 2 .42<br />
to 7 .48) and 1 .77 (95% CI, 0 .98 to 3 .19), respectively,<br />
C, wianai IMUtulg ta<br />
Occup,tovU sat .ty and HeaNn Cr+crnatut owo<br />
of Autt~ a nov, wrtn tM Orapon F4atm D-san,<br />
PoruanC<br />
a.wrru r.a, .st: to l.wrsun, sur, urvv«,M kMdrcai<br />
Gna+ D.partm.nt of Patnaogy 1901 P.raao St .<br />
N.w. OMU,¢ U 70112. 1393 (D+ FonUurn)<br />
IN JANUARY 1993, the US Environmental<br />
Protection Agency (EPA) issued<br />
a report on the reapiratory health effects •<br />
of paaaive amoking in which it concluded<br />
that environmental tobacco smoke (ETS)<br />
is a human <strong>lung</strong> calrlnogen, responsible<br />
for approldmately 30001ung <strong>cancer</strong> deaths<br />
per year in US nonamokera' A total of 30<br />
epiderniologic studies conducted worldwide<br />
were included in the EPA risk aateasment,<br />
including 11 studies conducted<br />
in the United States?-'t Of the US atudies,<br />
the report of findings from the fitst 3<br />
years of this multicenter study' contributed<br />
the greatest individual study weight<br />
to the US aumrnary relative riak (ER)<br />
estimates for <strong>lung</strong> <strong>cancer</strong> . 1 .19 (959o con-<br />
5dence interval [CI), 1 .04 to 1&i) assoaated<br />
with "ever exposed" to npauaal ET5<br />
and 1 .38 (95% CI, 1 .13 to 1 .70) for the<br />
highest level of spousal ETS <strong>exposure</strong> .<br />
The weight accorded this etvdy in the<br />
EPA report reflected the large number of<br />
tifetime nonsmokers with hing <strong>cancer</strong><br />
(n-4X), as well as the study design used<br />
in thia caae-control study . This study was<br />
designed epecifScslly to evaluate the role<br />
of ETS <strong>exposure</strong> in the etiology of <strong>lung</strong><br />
<strong>cancer</strong> in lifetime nonemokera .<br />
Two large US studies have been publiahed<br />
aince the preparation of the EPA<br />
teport~ Becauae t}>ese studies are aimilar<br />
in size and scope to our first report,<br />
their findings would have had a timi)ar<br />
impact on the summary US risk estimates<br />
. Brownson et ala observed no increased<br />
risk in the ever-exposed category<br />
for spousal ETS (adjusted odds ratio<br />
[OR)=1 .0; 95% CI, 0 .6 to 1 .2, however,<br />
the CI indudes 1 .19, the US summary<br />
point estimate . The highest <strong>exposure</strong> aategory<br />
(greater than 40 pack-years) in the<br />
study by Brownson et a] yielded an RR<br />
estimate of 1 .3 (95% CI, 1 .0 to 1 .7), quite<br />
similar to the US "high-exposwe" alunmary<br />
estimate of 1 .38. In the secorld study<br />
by Stockwell et al," the RR estimates<br />
are among the highest reported for US<br />
studies : 1 .6 (9596 CI, 0.8 to 3A) for ever<br />
exposed and 24 (95% CI,1 .1 to 53) for 40<br />
or more smoke-yeara in adulthood .<br />
Thia report extends the findings of<br />
this multicenter study on completion of<br />
2 additional years of subject accrual .<br />
METHODS<br />
Ihe methods and procedures followed<br />
in thia study have been previously deuribed<br />
in detaIl.' The study was & population-ba>,ed<br />
case-control study of hing csnces<br />
in rvomen who have never used any<br />
tobacco product- Eligible cases included<br />
racnoes-ropically rnnSrmed prvnary carcinoma<br />
of the <strong>lung</strong> (International Claaaifioation<br />
of Lhaenara, Ninth Rrvirion [1CD-<br />
9), code 162) that .vere diagnosed between<br />
December 1,1986, and November30,19£?f3,<br />
1752 JIJUA, kna 8. 1994-Va 271, No 22 Tooacco Srrnko antl Lunp Cancer-Forvr)wn tt a+<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Y~ g (y . °' won<br />
n :, ~3<br />
I ei ;; e~~"'wo<br />
- o aa ~so~ - s :,ah - 0<br />
s fV N<br />
I<br />
2029051465<br />
Y!II ~~' oogo ~ ~'<br />
oc{c~y~ (,<br />
~~S~~Y~~Cs~"~ ~~°~,a~°~~~<br />
~g~s~ 8<br />
~~ ~ E~ ~ 8°~ ~ ~E fl^°~~<br />
~<br />
2*<br />
Y 79<br />
y Y<br />
qllli'I 0 s~-~ .5d<br />
-s Ls
0 0<br />
e<br />
.<br />
0<br />
,<br />
1<br />
years (7`` ,6) with a similar proportion of<br />
controls in this age group . As noted pre•<br />
viousl} .,= the age distribution in this series<br />
of female Lifetime never smokers with<br />
<strong>lung</strong> <strong>cancer</strong> is older than all female <strong>lung</strong><br />
<strong>cancer</strong> cases in the Surveillance, Epidemiolog}•,<br />
and End Results (SEER) Pn}<br />
gram, 1973 through 1988 .°<br />
The largest proportions of hulg <strong>cancer</strong><br />
cases (58 .5%) and controls (61 .1%) were<br />
Tahite. A larger proportion of cases were<br />
uelf-identilled as Asian American and Hispautic<br />
and a arnaller proportion as A5-ican<br />
American (btacks) compared with convrols<br />
. Approaimately 42% of cases and<br />
38% of controls reported an annual household<br />
income of less than L20000 per ye.u'•<br />
Compared wit}t controls, <strong>lung</strong> <strong>cancer</strong> cases<br />
tended to have A lower level of education :<br />
66.35-r of cases and 52 .6% of controls had<br />
no more than a high school education .<br />
Table 2 displays the estimated RRs of<br />
<strong>lung</strong> <strong>cancer</strong> associated aith ever living<br />
aith a spouse who smoked by type of<br />
tobacco . A 30% excess risk associated<br />
with tobacco use by spouse(s) was ob-<br />
6erved for all histopathologic types of<br />
<strong>lung</strong> <strong>cancer</strong> combined (adjusted OR=129 ;<br />
P< .05), for adenocarcinoma of the <strong>lung</strong><br />
(adjusted OR=1 .28 ; P< .05), and for primary<br />
<strong>lung</strong> carcinomas other than adenorxrcinoma<br />
(adjusted OR=1 .37 ; P= .18).<br />
The only individual types of tobacco asnorinted<br />
with sigllificantly elevated risks<br />
of <strong>lung</strong> <strong>cancer</strong> are cigar- and pipe-smoke<br />
<strong>exposure</strong> for bronchogenic carzinornas<br />
other than adenoc$rcinoma : cigars, adjust<br />
.ed OR=1 .88 and PS .01 ; pipe, adjusted<br />
ORtt1 .79 and P= .Q2 .<br />
The estimated RRs of <strong>lung</strong> <strong>cancer</strong> associated<br />
with pack-years of <strong>exposure</strong> to<br />
spousal ETS are presented in Table 3 .<br />
1nc:,easing risk of <strong>lung</strong> <strong>cancer</strong> with increasing<br />
pack-years of spousal ETS <strong>exposure</strong><br />
is observed for all <strong>lung</strong> carcinomas<br />
combined and for the two histopathologic<br />
subgroups . The risk estimates are<br />
similar within the histopathologic subgroups<br />
; however, the trend is 6ignificant<br />
only for all <strong>lung</strong> canc<strong>ets</strong> combined (P= .03)<br />
and pulmonary adenocarcinoma (P< .05) .<br />
When the analysis was restricted to selfrespondents<br />
only, similar estimates of<br />
risk of <strong>lung</strong> <strong>cancer</strong> were observed with a<br />
trend of increasing risk of <strong>lung</strong> <strong>cancer</strong> at<br />
inavasing levels of <strong>exposure</strong> (P= .03) .<br />
Exposure to ETS during childhood and<br />
adult life 5rom multiple sources was evaluated<br />
. The risks of <strong>lung</strong> <strong>cancer</strong> aasociated<br />
with household ETS <strong>exposure</strong>s during<br />
cluldhood as a resuh of father, mother, or<br />
other household member amoking are<br />
shown in Table 4 . None of the RR estimates<br />
sigTtiScantly dit7ers 5rom unity . The<br />
association of cumulative years of household<br />
<strong>exposure</strong> to ETS during childhood<br />
with <strong>lung</strong> <strong>cancer</strong> riek was evahtated (Table<br />
5) . No increased riik was associated with<br />
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cno+suroW urnry tustory 04 k/ng unc .r anp rrmployrr»nl n tyqn-re . p=.T+atront OA mautn 0oas r .t,a CI<br />
oo0w.n~* ax.N .<br />
Tae,. 5-.4aaoa.u«, sah~..n Rmk ot Lunq Cancar " ChAdhood SmokwYSars of E*OSUro Anwnq<br />
Nonsrrmokirlp Women (Sen•rasponoents Onty)'<br />
ChllOfaod tmo~Y"rs<br />
CtuM oR<br />
A4jurMd OR<br />
ol How».MM Eapoaurs Ca.as GontroM<br />
("1. CI)<br />
(f41. CI)<br />
AN kmp nrarlornu<br />
0 148 ... 100 100<br />
1•17 ss 291 asam73•1s2t oes(07s1as)<br />
,16 146 aas o90(07o-117) 0t6(067 .116i<br />
Tr.no k . 56 TrnC R.,36<br />
Aa«,oaaruhon>a<br />
0 120 ... 100 1 00<br />
1 .17 73 29+ oo3to67ns9 ; 0sato6slzv~<br />
ae 123 .ea owro71•1sa, 0a9(06&11A)<br />
TrKW A, 66<br />
Tror1C P*< /3<br />
oe,.r n.aa~tycs<br />
0 s6 u, t .oo 100<br />
1•17 22 291 120(067•214) 1s2(o72•24 1,<br />
:16 23 aas o 75 (0 .3-t ss) o .ns (0 .7 .1 sa)<br />
Tr .M P. 13 Trsno Pr 56<br />
•Atlµx1 .0 fa .0q rscee swoy ar.a . .bucaoon, huts rp .ud+s mW a.pp+.m.nu' vnam+n rW0x dyury<br />
ybist.rd . lanvy hrtory 0( k.ap urxnr, r•rstl .mpaymen/ n hgr.rxx Ocayrlt.orn O(i rd,cafts a0ds rato Ci,<br />
oonne .no* w.rva<br />
increasing duration of smoke <strong>exposure</strong><br />
during clu7dhood . Cku7dhood smoke-years<br />
were urtlawwn for a large proportion (20%)<br />
of the interviews with proxy respondents<br />
and for 6% of the interviews conducted<br />
with the study aubject. For those interviews<br />
with data avat7a.ble to alclilate<br />
snwke-years, 54% of proxy respondent<br />
interviews ve 88% of direct study subject<br />
interviews reported no <strong>exposure</strong> during<br />
etu7dhood . The data presented, therefore,<br />
are for analyses restricted to self-respondents<br />
. No differences were ob6erved by<br />
pathology review ttat•us ; dietary cholesterol<br />
intake ; level of the fruits, vegetables,<br />
and aupplemenul vitamin use index ; age<br />
group; or educational attainnlent, Black<br />
study aubjert .e had a twofold elevation in<br />
risk ln the highest <strong>exposure</strong> category, and<br />
Alr'ans showed twofold reduction in risk<br />
at this level ; however, these two point<br />
eatirnates did not signi8cantly differ . Re-<br />
stricting years of ETS <strong>exposure</strong> during<br />
cht7dhood to those from the mother ytielded<br />
similar nonsig'rti6cant trends .<br />
Table 6 presents the estimated RRs<br />
aaaociated ait} : adult ETS <strong>exposure</strong> (ever<br />
exposed and years of <strong>exposure</strong> by in(b-<br />
.idual rotuces during adldt life) . Elevatiorw<br />
in risk are associated with increasing<br />
duration of <strong>exposure</strong> at home (trend<br />
P-.11), on the job (trend P= .001), and in<br />
social settings (trend P= .002) . TT1e inereased<br />
risk of <strong>lung</strong> <strong>cancer</strong> among women<br />
ever exposed to ETS during adult life in<br />
the household is 24% ; in occupational settings,<br />
M ; and in social nettings. 60'`.~ .<br />
The pattern of response is aimilar in the<br />
two histologic subgroups ; however, the<br />
tests of trend are statiatucally tigtli8cant<br />
only in the largest subgroup, pulmonary<br />
adenocarcinoma<br />
A,< shown in Table 7, when all sources<br />
of <strong>exposure</strong> to ETS dtu-ing adult life are<br />
. 1 ,w.v,. Ju1e 8 tASa-va 27 t, No 22 Toaacco S+11oke and lug Cance{--Fc*ltnam el aI 1T35<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
5m
of the study, inereased risk of hmg <strong>cancer</strong><br />
from adult ETS <strong>exposure</strong> was stronger<br />
for adenocsrcinoma of the <strong>lung</strong> than for<br />
al7 cell types combined? That ffnding is no<br />
longer apparent with the additional cases<br />
of each cell type . Although the estimates<br />
of RR for pulmonary adenocarcinoma are<br />
not different from tHose for other cell<br />
types, adenocarcinoma of the <strong>lung</strong> is by<br />
far the predominant cell type diagnosed<br />
in women with <strong>lung</strong> <strong>cancer</strong> who are lifetime<br />
nonsmokers, and oo the ef5ects of<br />
ETS <strong>exposure</strong> may be particularly rel•<br />
evant for this histopathologic cell type .'<br />
More than 75% of the cases in this study<br />
were diagnosed with prim.v-yy pulmonary<br />
a.denecarcinoma, twice the proportion of<br />
adenocareinoma of the <strong>lung</strong> diagnosed in<br />
all US women without regard to smoking<br />
history: 37% among female <strong>lung</strong> <strong>cancer</strong><br />
cases in the SEER program .° In other<br />
studies of E'I5 in female nonsmokers in<br />
which histopathology was reported, adwnlocstrcinoma<br />
comprised 60 K or more of<br />
nll cases in six of nine studies .L'"'6' ' In<br />
the other three studies, the proportion of<br />
udenocarcinotna cases ranged from 43%<br />
Ro 549E ." 1' Differences in the physical and<br />
themical properties of sidestream smoke<br />
compared with mainstream smoke, including<br />
the distnbution of the vapor and particulate<br />
phases and the concentration of<br />
Imov.-n or suspected carcinogens!' combined<br />
uith ditferences in inhalation, nasal<br />
vs oral, may yield a higher proportion of<br />
peripheral adenoatranomas .u<br />
Ddisclassification of disease status was<br />
minimized in this study by the eligibility<br />
rriteria (microscopic diagnosis required)<br />
and an independent review of diagnostic<br />
ataterial that was completed for 85% of<br />
the cases . The amall proportion of cases<br />
found ineligtble by independent review<br />
may result from the populat.ion•based tumor<br />
registry affiliation of four of the five<br />
study cent.ers. The consistency of the findings<br />
w-ith and without nonreviewed cases<br />
supports the contention that the study<br />
results were not measurably altered by<br />
incluaion of ineligible caees .<br />
Misclassification of eversmoker6 as lifetime<br />
never smokers is more problematic .<br />
'I11e objective of this study was to evalu•<br />
ate the risk of <strong>lung</strong> <strong>cancer</strong> in women who<br />
had never smoked . At present there is no<br />
known biomarker of lifetime tobacco use .<br />
Cotinine, the major metabolite of nicotine,<br />
is the most widely accepted biomarker<br />
of current (I to 2 days) tobacco<br />
<strong>exposure</strong> and is useful for distinguishing<br />
current active 6wrukers from current nonainokers<br />
.'"' The proportion of reported<br />
nartsntokersin the present study with a<br />
cotininelcreatinine concentration above<br />
100 nghng was 1 .9%, the same proportion<br />
vrith a concentration above 100 nghng<br />
obeerved in a 10-country, multicenter<br />
study of self-reported ETS eupo6ure"<br />
.lAMN, Jwte 8, 1 ;W-VO( 271, No 22<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
TaM. 7--Aauoaanon gfiww Rrk 0t Lunq C .nar sna AdAawod S+rwk.-Y ..n d Expu>r. Amx,q<br />
/lonunoWnO wom.n•<br />
~~<br />
~ cn,a. oa aeWs+ .e on<br />
c., .. oo araft tts+. Co (ss+ cu<br />
aJ1 t.,Rq C.rtMnww (Aw IL.poneenb)<br />
0 ,6 tte 100<br />
1•11 74 299 076(050-116i<br />
122e 136 307 111 (0755163)<br />
29-47 163 3W 12 .(0eA . 1 921<br />
a+6 163 265 1 $10 .03•2 .23)1<br />
Adenoc+rdnae . (AM OLepen6r++tt)<br />
Tnntl fi . 0001<br />
0 36 11e 1 .00 . .<br />
1•11 6. 239 0 7< (o 46L1 19)<br />
1226 1io K7 1 .17(076•1 e1)<br />
20.r7 112 304 121 (07'6•166)<br />
n46 130 M 1 .61 (1 .0b217)1<br />
TnM A. 0002<br />
()Hu . N/lqoiopkal Typ.s (N( /I+spondvrtn)<br />
0 12 118 100 _ 100<br />
100<br />
062(052•1 .29)<br />
112(o7S17o)<br />
135(oe420a)<br />
1 .74 (1 14-2 65)1<br />
Trtntl P. 0001<br />
1,00<br />
074 (0 .•u .1 23)<br />
1 .15 (o 73-1 tJt<br />
119(0e1•20a)<br />
1 77 (112•2 6011<br />
Tnrd H. 0001<br />
20 239 0e2(039-174) 117(052•262)<br />
122e 26 307 090(o4t-162) 1001oA621e ;<br />
24-a7 41 304 1,33(067•261) 1 .58(076331)<br />
:i6 13 265 1 .Y.!(061•216) 1 .76(063.375)<br />
Teur.tl P. 12 TrmO W 05<br />
Aut u" C«otr,a>re ".w~onse(w or+ly)<br />
0 30 11e 1,00 1 .00<br />
;.11 53 238 00E(051•15A) 079(0W 42)<br />
12•2e 103 306 1 .32 (06t•210) 1 20 (0'A•1 94)<br />
2D-~ 7 110 304 112(09ti223) 14+(ot4231)<br />
:a6 105 265 1,56 (0,9cS•2 47) 1 .67 (1 B3•2 70tt<br />
0<br />
1•11<br />
122e<br />
29-47<br />
:i6<br />
AA.norarcMm .n . (s.n+wva,Wa o„H)<br />
TMr+tl P . 002 Tnrb h 0006<br />
23 11e 100 . . 100<br />
A1 236 0 66 (o 5} 1") 0 D 1(0 46,1 , 37)<br />
a6 306 1 46 (o 99•2 45) 1 31 (0 77•2 22)<br />
62 304 1,36(0f.1230) 139 to624 361<br />
91 265 1 76 (1 .06-2 02)1 115 (7 0P3 15)1<br />
Tnnd Fr,001 7rOrd 0. 0005<br />
om« rrwo1optu( Tw« (aas4. .PONOOP" onM)<br />
0 7 116 100 . . . 1 00<br />
1•11 12 236 0a5(031222) 0 91 (0 3A•2 .5)<br />
12•2e ls ao6 o 93 (0 .33•2 06) 062(031•216)<br />
29~7 ~ 304 1 55 (o 66•3 65) 1Ft (0674 03)<br />
14 2a5 0 69 (0 .35•226) 1 12 (o 42r2 96)<br />
TrMO R 49 Twntl P= 32<br />
'Atltuttod br p! . fTp* autly .rN *dY'.11qn. hUR{ . vpartbltt . >/Rtl uuryp+rmfnW VumA r1Wx bftay<br />
dw4surd, s.mry trstory d Mq umr, .nC .mpay*r»m n r,pn-rwK aoa.prba>t OFi rdcws oilos reeo . CI .<br />
oon6cs.np rr .naW<br />
tp< .os<br />
A higher proportion of controle than<br />
cases was exc]uded from the study s6 a<br />
result of elevated ooncentrations of urinary<br />
cotinineJcreatinine, 2.3% vs 0 .6% .<br />
(',ases were klenti4ed at ho6pitals, and<br />
aaeedng of medical records and physieLUU<br />
about the patient's current and past<br />
use of tobaxo preceded the screening by<br />
telephone and at the interview for all 6Ux1yy<br />
subjecw .'Itiia procedure may have eliminated<br />
some curnent amokers from the case<br />
series who would have been inclined to<br />
self-report as nonamokers in an interview<br />
format. Alternatively, some cases who<br />
would miareport smoking status may be<br />
less likely, because of health status, to be<br />
actively antddng and less &ceh• to be revealed<br />
than healthy, free-living controls .<br />
Other data suggest that <strong>lung</strong> <strong>cancer</strong> aa
i-11 33 91 0 7e (0 a4-1 30) 0 76 (o 40-1 tJ) 36 137 1 .SJ (0 96 J 52)<br />
12•26 41 97 0 91 (0 S2•1 58 0 00 (0 43-1 46) 86 2U2 240(1 .06-530)<br />
2947<br />
5_4 97 1 .20(071•20-4) 1 .16(06S-20e) E5 204 229 (1 .0+507)<br />
246 _ _ 53 90 1 .45 10 a5419)<br />
1 .77 (0 .96-J 19) 94 ia2 214 (129-62!)<br />
Trsnd Pe 04<br />
Tr.nd P. 01<br />
Aa laA4 Cwskro~ v. CsnaW (9+M+.pondwxs Only)<br />
0 Z3 71 1 .00 1 00 , 5 44 1 00<br />
Tisntl P.001J<br />
1-11 23 90 0 79 (0i1 .1 .52) 066 (0 54 .1 38) 29 137 1J6(066-510)<br />
12-2! 26 97 0 99 (0 47-1 67) 064 (032•12e) 69 201 J02(115-793)t<br />
2"7 i 97 1 15 (0 63-2 10) 104 (054-196) 67 2w 2 69 (1 10-7 59 )1<br />
za! 31 Do 1,20 (0 64-224) 1 14 t (0 69-2 60) 70 192 J~9(129-669)t<br />
Tmnd P. 26 TrMOR 17 Tr.ntl P. 004<br />
!<br />
'AOluatw tor a" n1a . .aucaeon . tiJOy Ar.. Iivits v"ub4s, uxJ sWWa"nW vTtamin vW .= . d.ury cho4sUrol, tartwy 1ysloryol kx+q ClnWr. rv+d vnpoyrrsM n t,p~nsk<br />
axupaoon Oq u o,ca .c o0as rac0. CI . oonhb .na nunnl<br />
tP< 05<br />
tF< .01<br />
Refusal to protiide a sample was similar<br />
among Liv-ing cases (19%) and controls<br />
(17%); however, because of illness and<br />
death, a higher proportion of the total<br />
subjects in the case series had no cotinine<br />
measurement . Of study subjects for whom<br />
no sample was available, 63% reported<br />
ever having lived with a spouse who<br />
smoked ; for study subjects with cotitilne<br />
detesTninations, 639(c of eligtble women and<br />
68% of excluded women reported ever<br />
having spousal ETS <strong>exposure</strong> .<br />
Analyses using a lower cut point (55<br />
mg/ng) for exclusion based on urinary<br />
cot.171ine concentrations provided slightly<br />
higher estimates of risk associated with<br />
ETS <strong>exposure</strong>, but the differences have<br />
little or no effect on study conclusions .<br />
Compared with recent large US studies,<br />
the proportion of proxy respondents<br />
for <strong>lung</strong> <strong>cancer</strong> cases in this study was<br />
small : 36.9% compared with 65% in the<br />
study reported by Brownson et al" and<br />
67% in the study by Stockwell et al"<br />
Nevertheless, it is important to evaluate<br />
wheth,er the 5ndings differ when proxy<br />
respondents are excluded from the analysea<br />
. The only appreciable difference was<br />
noted for childhood <strong>exposure</strong>s . Of those<br />
interviews with proxy respondents, 31%<br />
were conducted with the study subject's<br />
spouse and 48% with an adult offspring<br />
of the study 9ubject. These individuals<br />
had lived with the study subject and<br />
shared life experiences during the study<br />
subject's adult life, but not during the<br />
study subject's childhood years . The opportunity<br />
for misclassification of <strong>exposure</strong>s<br />
is greater, therefore, for childhood<br />
<strong>exposure</strong>s . The lower reliability for child•<br />
hood <strong>exposure</strong>s compared with estimates<br />
of <strong>exposure</strong> from a spouse has been noted<br />
previoualy!0"1 The consistency of finding3<br />
for adult-life <strong>exposure</strong>s in the total<br />
175E J.UA6.. Jtx1e 8, 1994--va 271, No 22<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
series and among self-respondents only<br />
suggests that systematic misclassification<br />
by proxy respondents for adult-life<br />
ETS <strong>exposure</strong>s was minimal .<br />
The inconsistency in the literature with<br />
regard to the association of <strong>lung</strong> <strong>cancer</strong><br />
with ETS <strong>exposure</strong> during childhoodl'<br />
"~123' may stem from the limited<br />
power of many of these studies, as<br />
well as difficulties in recall of distant<br />
events and/or incomplete knowledge by<br />
proxy respondents . The effect of each of<br />
these factors is likely to vary among different<br />
cultures, as well as by the proportion<br />
of proxy respondents in any given<br />
study . Failure to find an independent effect<br />
of childhood <strong>exposure</strong> in case-control<br />
studies might result also from the latency<br />
period of <strong>lung</strong> <strong>cancer</strong> and the age distribution<br />
of female nonsmokers with <strong>lung</strong><br />
<strong>cancer</strong> . Lung <strong>cancer</strong> arising as a result of<br />
childhood ETS expoaure would be expected<br />
to occur relatively early in life .<br />
Even with a latent period of 30 or 40<br />
years, these casea would be young>er than<br />
60 yeara at the time of diagnosis, aad<br />
such caaes comprise a small part of the<br />
total case series. No differences were observed<br />
in this study, however, when risk<br />
assoriated with 9rnoke-years of <strong>exposure</strong><br />
during childhood was examined for subjects<br />
in the case and control groups who '<br />
were younger than 60 years compared<br />
with those 60 years of age and older . A]though<br />
no independent effect of childhood<br />
<strong>exposure</strong> was observed, such <strong>exposure</strong><br />
appears to modify the effect of aubsequent<br />
ETS <strong>exposure</strong> during adult life.<br />
Twofold increaaea in risk are observed at<br />
all levels of adult <strong>exposure</strong> for subjects<br />
who had any childhood household <strong>exposure</strong><br />
compared with those who did not .<br />
Individual nutrients and micaonutzienta<br />
associated with <strong>lung</strong> <strong>cancer</strong> were included<br />
100<br />
1 93 (0 99d .a6)<br />
24J(1 .07•551)t<br />
294 (1 16-601)t<br />
325 (1 42•7 46)S<br />
TnnO P. .00o6<br />
in preliminary analyses . The final model<br />
includes an index that captures the intake<br />
of both dietary and supplemental antioxidants<br />
and a variable for dietaryintske of<br />
choleaterol adjusted for calorsea . In this<br />
study, high intake of hu.its and vegetables<br />
and supplemental vitunins is asaociated<br />
with derreased risk of <strong>lung</strong> <strong>cancer</strong>, and<br />
dietary cholesterol is associated svith incrv.a9ed<br />
risk. Although it has been suggested<br />
that low intake of csrotenoids or<br />
>}tritb and vegetables and high intake of<br />
dietary fat are potential confounders of<br />
the association between ETS and <strong>lung</strong><br />
<strong>cancer</strong>!4 this was not observed in our atuiiy<br />
or in the recent report by Kalandidi et<br />
aL" In addition, similar trends of increased<br />
risk of <strong>lung</strong> <strong>cancer</strong> asaociaied with ina~<br />
ing smoke-years of <strong>exposure</strong> are apparent<br />
at all levels of both dietary cholesterol<br />
intake and the index of fruits, vegetables,<br />
and supplemental vitamin use . Household<br />
radon >reas measured by 48-ho(ff paesive<br />
diltusion canisters in a sample of study<br />
subjecte' homes, and these scrcening levels<br />
in all five geographic areas were uniformly<br />
low and not associated with casecontrol<br />
atatua . These obees vations i.ndiate<br />
that the strong association in this<br />
study between adult ETS <strong>exposure</strong> and<br />
<strong>lung</strong> <strong>cancer</strong> risk cannot be attnbuted to<br />
any likely amfounder .<br />
A positive dobe response between ETS<br />
<strong>exposure</strong> during adult life and <strong>lung</strong> <strong>cancer</strong><br />
risk was found .+hen individual sources<br />
of <strong>exposure</strong>, such as household, occupational,<br />
and social settings, were examined<br />
separately, and this pattern of risk<br />
was clearest when these <strong>exposure</strong> sources<br />
were considered jointly . The point estimates<br />
are somewhat higher for <strong>exposure</strong>s<br />
in occupational and social settings than<br />
within households, but these differences<br />
are not statistically signi8osnt .'I11e higher<br />
TOba= Smolce and LunQ CanCm-fonUlam et sl
del<br />
tke<br />
UC]a<br />
of<br />
his<br />
tles<br />
ed<br />
3nd<br />
Ql-<br />
a of<br />
ang<br />
udy<br />
i et<br />
lbed<br />
eas .<br />
ual•erol<br />
ttvtd<br />
sive<br />
udy<br />
lev<br />
]mi-<br />
-Asemdithis<br />
and<br />
-d to<br />
estimates in the former settings may retlect<br />
etunce, some recnl) bias, or the potential<br />
for a larger nt.lmber of smokers<br />
and smoke <strong>exposure</strong>s in these settings,<br />
Workplace ETS <strong>exposure</strong> has receivedless<br />
attention than domestic ETS <strong>exposure</strong><br />
in studies of <strong>lung</strong> <strong>cancer</strong> to date ;<br />
however, monitoring of ETS or its conatituentL<br />
in workplace settings has demonstrated<br />
detertable markers of ETS by<br />
penwnal air monitoring and biomarke .ls<br />
with average concentrations similar to<br />
residential levels but writh higher maximwn<br />
v»lues .l In a etudy of workplace<br />
ETS, the correlation between number of '<br />
smokers encountered during a workshiil<br />
and personal sampler nicotine concentration<br />
(micrograms per cubic meter) was<br />
0 .'6,.`y (Pj <strong>cancer</strong> tn Texaa, !n : Iltull M,<br />
CoeTta F, K111.LwQ CanCeT' Calllei and PreUentsm%<br />
. Ne- York. NY . VertaQ Chemu lntern.tional<br />
lnc~ 198483-99,<br />
{. Chan WD, Funa SC . Lung <strong>cancer</strong> ]n rwa+moken<br />
ia HostgKortt In: Grundtnann E, ed Caue+ Campatqn,<br />
Vl. Caner. Epdernwlapy Stirtt;art, Germany-<br />
Gauv Fischer Verlar. 19EL19&2t2-<br />
7 . Carre. P, Fonthun E, Psekk L Lm Y, Haanrtcl<br />
W . P.etiv'e amold4 and katg euwer . 1-aeaa 1989 ;<br />
L5Ws5e7 .<br />
{- Gw Y, Blot WJ, Zheng W, et al, Lung eancer<br />
amona Chuuse women . !nt J Canerr1fl67 ;itr•604eo9<br />
1, GarGnkel L . Auert,arJ 0, Joubert L. lnvdutr<br />
ury alrroidng and Imtt <strong>cancer</strong> . a cue-eorttrd study .<br />
J Natl Caweer lut 1985,75 :463-469 .<br />
10, Gen= G, LianQ ZH, Zhant GL On the relatim,<br />
alup bet .+een smoking and fernale <strong>lung</strong> <strong>cancer</strong> . In :<br />
Aolc 1(, Hutmichi S, Tominags S, edsSmoktnq<br />
andHwlth Amaterdam,theNetheriands,Elsevier<br />
Science Publuhen, 198E :4£~3 1&6<br />
11. Humble CG, Samet JSf, Patluk DR . M .mage<br />
to a emoker and <strong>lung</strong> <strong>cancer</strong> risk . Am J Pwblic<br />
Healtk 1W4,77:59es-602<br />
12 Inoue R, Hzreyuru T Pasdve emolartQ and hrrtg<br />
oanorr in women ln Aoki ed, Hiumiehi S,Tornuuga<br />
S. ads Smokinq a+d Nealth Amatenlam, the Netheriands.<br />
Elsevier Soenee Pubtuhers; 198&283-285,<br />
11- Janerich DT, Tbompaon WD, Vanla LR, at al<br />
Lung <strong>cancer</strong> and <strong>exposure</strong> to tobacco rmoke in the<br />
hoasehold, N EKg1 1 Med 199tr323 .632-836<br />
14, Ktbst GC, Vlynder EL. Lung canaer in nonamoicen<br />
Caerer 19Bf ;53,1214-1221 .<br />
ls. Kahrdidi A . Kuaouyanni K, Volopoubu N, el al .<br />
Pe.dre arwianQ ard diet in the etwbr• of htng anoer<br />
amonQ nonmiokat Ca~ Ca u.ce Cowtrol. 19Btr<br />
1 :1521.<br />
1C Koo LC, Ho JH . SaR D, Ho CY . Neastaements<br />
of paasive amokinQ and eetirnates of htng urxer<br />
rlak amortg notumoklnY Chinese femtk..l+u J Canosr<br />
1987 :39 162•169<br />
17. Lam TH, Ktug 17?!, W oetK Cld, et al SmoinnQ,<br />
paice m o1anQ, and hutologtrul typee in hwq atscer<br />
trt Htxtg Kong Cl»nae vornen . Br J Cawcrr, 198'116 :<br />
E73-b75<br />
I& Lam V+'K. A Cltxicd ard Ep6demwlopieal Sts+dy<br />
c/CarcinornaoftkeLunptnHonpKonp HongKoap-<br />
Unh'vsity of Hoeg KortQ I965 . 7heda,<br />
19 . Lee PN, CLarnberiain J, Akerwn YR, Retation<br />
.ltip of paaaive tmokinQ to risk of hutg <strong>cancer</strong><br />
and other emokmg-as.ociated dueues, Br J Caeeer<br />
19B6 ;Si97•]05<br />
!6. Liu Z, He X, Chapman RS . Smoidrty and other<br />
risk f.aon for hutg <strong>cancer</strong> tn XtrrtweL Chins . l.t<br />
J Epitemiol. 1fle1Z-26-S1 .<br />
21 . Per.hagen G, Hrubec 2, Sveruson C . Pt.aive<br />
aatoidltt and iutte <strong>cancer</strong> in Swedish w•omen• Atn J<br />
Epidem wl 198-7;126 :17-24 .<br />
!t Shimia H, Idorislilta )i, B[isww K& et al A<br />
a.se-crontrol stvdy of hung <strong>cancer</strong> tn norAmsoltint<br />
wornen . ToAokw J Erp Med 1988161 E89J97,<br />
i3. BobGx T, SauJd R, N akayanu N, et al• PaasSve<br />
asnoMng araonQ nonarnolW women ard the rek .tionahip<br />
between ladoor aSr pollution .nd hutt nneer<br />
ksddcnce . C,aw No RtwAa, 11DU,J6 :S19S33•<br />
14, Bvensaon C, P<strong>ets</strong>}um G, Kkxniaxk J . Smah-<br />
Ir>z and peulve atnoidrtl in relation to kum <strong>cancer</strong><br />
in woenen- Acta O.eol. 198MdZ;iL29 .<br />
T[• Iridtopottba D, Kilandidi A, Bparx. L lausQ<br />
eanoer and passive amoidrg , Lawert .19B33•667-668ti.<br />
M'u AH, Hender.on BE, Ptke HD, Yn NC. SmokisQ<br />
aa,d othet riak faRora for kmc anaer in wanen .<br />
J Nail Cawar. lsui 1985 ;74:747•751 .<br />
!7 . R'u-Williaau AH, Samet JH . Envirorunental<br />
tab.c-co mwke : <strong>exposure</strong>-reeporuu re4tioelehipe in<br />
•pidemiolopfc ntldiea . Ruk Anal 199(T,1tr39-48-<br />
2& Butkr TL, The Relatuouktp ojpausva Smok<br />
aap to Vanow Healtl Osleomea Awonp SnVnlh•<br />
Day Adtrxtuu tn Caltfomia Loe Antnles . Univenny<br />
of Calilornu-Loc Ano ke ; 1968 Tbeeiu .<br />
!!. Gar4rtkel 1 . . Ttme tmds in kc* aenec n+oeubt y<br />
annew mrmokm and a rwtr on prwve anoionQ<br />
J Nat1 Cawcr* lntt 19817B :1061-1066<br />
8!. Ha+yurr TCanocr tnoetality fn wicnmlang<br />
.ortscnwSth aa/o1miQ lw .banda based on a lar{t.ok<br />
eotsort "y m Japan Pm• M.d 19B4;IIh68Jd90<br />
11 . Hok DJ, Gillia CR, Chopr . C, Ha.nhorne VN<br />
Paative unolanQ and nrd areepira ory hsalth tn a<br />
t<strong>ets</strong>eraJ popuLtion in the west of SeoU.nd. BMJ<br />
I>189~ t2112 7 32- Brawoe RC, Akavvt}a MC, Hock ET, Loy<br />
T8 . Paadve rnoMnt and 1ur1g anaer tn nonamok ,<br />
bftjwomen, Am J Pa bltc H .a1tk 19Q=,15251 S3G .<br />
fL Bt«kwell HG, Goldtnen AL, Lytran GH, et a1<br />
Earborune.ntal tab.nv arnoke and hrY <strong>cancer</strong> risk tn<br />
aanetwidrc wonun J Nail Cewrr hue ICfQ8/a 417-<br />
1422<br />
34 . Haley NJ, Axelrwd CY, T11ton fLA, Va}idation<br />
*( seu-reported anokint beharror bioctsenucal<br />
an.lyca of eotinine ar,d thioeyaruu. Am J Pybl c<br />
FleaftA 1983 ;73:1bD4-= .<br />
i6- Largone JJ, Gjika HB, Van Vtmalu . H . NKa-uK•<br />
a1d its rnetabohtts : tadiaunmuno.uays for tucounc<br />
and cotittine, B a'kemittry 19T3,1r5Q2SSa36 .<br />
K. Riboli E, Preswn-ldart n S, Saracn R, et al<br />
Expoeure of nonamoldn6 vomen to en~-iralmenul<br />
tabac•co mwke : a ten eountry collaborative atudy .<br />
Caneer Cavu. Control . 1M,1'1A3-ffi2 .<br />
17. Jarvv NJ, Tttrrutall-Pedoe H, Feyerabend C,<br />
Veeey C, Saloo}ee Y . Comp.rison of tests used to<br />
dittulfttiah emokers from nonmsokers . Am J P~b<br />
1u Healtk 1967 ;77 :1435-1438,<br />
SL Haky NJ, Coloaimo SG, Axeb-.d CH, Hami R,<br />
Sepkovic DW . Bioehenval ralidation ot .elf-ropotted<br />
expoaure to enviratmental tah .cco smoke .<br />
Et,oron RestarrA 1989,4J.17i-M<br />
38• HoEmaltn DW, Haley NJ, Adams JK', Brun .<br />
aeaan KD . <strong>Tobacco</strong> aideatrum talsoke : upt,ake by<br />
aonmsolten, Prer M .d 19& ;1~~615,<br />
a Hu .txn ME . Boyd G . Boyd D . et al Psniave<br />
a61 saokaS on eoeartrseal aitiine Eiat~u JA![A 19eia,<br />
ffi7-9TL<br />
41 . Schkaaetmann JJ . Ca.e-Ca+tml Strdu<br />
: Oxford<br />
. !krnpn, Conduct, Analyeu, New York, N5'<br />
University Preu ; 1982 .<br />
4t KYstbatan DG, Kupper LL Margemnem H, Ep<br />
demsobpu Reamircklannripla ad Quowlimtur<br />
MdAoda Beltnatt, Calif, Lffetune LwrtilV Pubbaa,<br />
tims; 1962<br />
13- Rees LAG, Hankey BF, ltilkr BA, Hartman<br />
Ald, Edw=rds BK Co%cer Stafut rs Rmrsr J9'd<br />
tA Bethe .da• Md : National Canoer Inrutute : 1991 .<br />
152-V123, NIH publintion 91-Zf89 .<br />
44. Committee on Parive Smolmt4, Board on Enrr<br />
rarutsental Studies and ToodeolV•, Nauotul Reaeard,<br />
Cauta7 . Ent~rowrwulalTobarcoSmokr Jd~nuq<br />
Erpoevres awd Ataeaaenp HrohA E1Tecu v,• ..huy<br />
tan, DC: Natiotsal Academy Pre .s; 1996<br />
4& Wynder EL Goadaan lfT . Smoidne and big<br />
t.mr. wne tmrodved i.nlaa Erdnn usl R", 19Hi .<br />
k177-l07 .<br />
16 . Pron GE, Burch JB, Ho .ve GR. iG7kr AB The<br />
reliabllity of pusive amobrq kiatoeiee reporned in<br />
4 taae-Cont.rol study d yuatt <strong>cancer</strong> . AM J Epuir<br />
sRiol, 1988;127367-2'f3,<br />
47 . Coultai DB, Peake GT, suett JY Quealon .<br />
saire araea .ment of Hfetfine and rrcent expoRure to<br />
entironrnental tabuM arnke, Aat J Epid.niiol<br />
1lRP 11Cr33R-b/7 .<br />
46• LeNaretund L, N'tlkina LR, Hankin JH, Haky<br />
NJ, Dietuy patterns of fevule aawtwkrrx with<br />
u+d .rlthout <strong>exposure</strong> to emironmemul tobacro<br />
amoke . Ca .err CaY.y CoRtrd . 1991 ;2 .•11 • I6<br />
11. Couha. DB, Baznet JM, MeCaMy JF, Spen<br />
tier JD A personal moetftoeint study to a.xm<br />
veStpLce <strong>exposure</strong> to envirr,nlnental tohacoo<br />
crrqke . Am J Prb1K H.altA 199PA09hti 99(,<br />
i4 Brtauxnunn KD, Cox JE, Hofhcunn D Analy •<br />
.ia of tobaecoapecific A"•nitrosamines In tndoor air<br />
C.xiKO9eweau1992131415-241fi .<br />
-1,D1 dl 1 ,IAAAA, ,kxle 8, 1984-Vol 271, No, 22 <strong>Tobacco</strong> Srnoke and Ltrsp CarKx - Fontr am el al 175i<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
I<br />
.<br />
q+ r . a-el +•.~, w•!L>.r.+w• rtr r<br />
t~ w+..t.n t.ro6. .% a w.w.a ., u<br />
Lung Cancer in Nonsmoking Women : A Multicenter<br />
Case-Control Study'<br />
[(ittbett, T . a{ . fonfham! Ie(aye Ce:enes, Arwu W W<br />
WIIlitml, Ptltl ltrsotds, t.a+nond S . Ctetnber},<br />
t'etrici/ A&uitttr, Yi .ien 14' . Chen, rt,tt sord,<br />
Ton1 jkIttrmtn, Donild F . Arntin, lonathajk Uf/,<br />
and S Dw4ld CrrenLer•{<br />
p.•p.A ~,r•. e+etA.Mer• lt..w. .•u lurr l>~+sR. W4[J Cwn<br />
.- abrnr tw•,w lo+u It t M f . r C v v. C I Drs+"~<br />
p re+ ..ir t .! Ce•,~•,,nnr watwt V++rn~. " C~<br />
tw e.+Yewr Cl1,teMd eCC)l l~ v . v. 1 C'a .mr L1.rr+, .. .. r<br />
terrq, trwxr t~+'r+•t. Cwr ."v Ir t, D tA .l 0••..• et<br />
te.+-a+o= (~ tr«-v, kM.ofve.rwrc wrrth AA..,<br />
e . : tiu iCtt) it f C 1 t 1 kbo v r .A+t arreR tJw.e•t•+r<br />
wj+tr. krcr C~r uwrre+` 1r.e~ f70)D tr A t,<br />
. : Cs`rrw e-V. wrt- 1.NW . CaJ~rnr M7)p<br />
rr t 1 ..,r AcM,-v,e{.w Crrr4p .r waK .e<br />
Nr+u... . 1tr,m t70)O It D C I<br />
Alrira n<br />
Tl.e alroci .tion 16et-ren etpoeurt to rmrironaw++ts(<br />
tob&ccm tmole end Ivnt C .ncer in fern .te Wttrmt<br />
non/moltri .tt t .alutted utint dau Collected durinj<br />
the firrt 7 tu+t of an ontoinS uk .eontrol aardt . Thit<br />
urSt, tnuhicenttr, poputetion•btud ttudt war<br />
deutntd to min(rni :e torne of the methodo(ot
,1 lsy Cerw M Mwwft.tM11,60"<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
erntiuuonl and cLssrf,catron of tht h .uopttho+o~ca1 ct6<br />
ol9r<br />
Kf Reu(f ay .es Two control R oups ex+e w++h cD+on<br />
<strong>cancer</strong> end ont from the Ienert,t popu4tan . an neirCSed<br />
6ot cese•control comp.ntont Ddfetentul reutl brc.Yrn<br />
a+ses end co4on <strong>cancer</strong> tontrofs should bs te+m+mutd<br />
Nnce both `roups are umlLriy tesosrvited to rec.aU earyer<br />
eraaoaxrs .<br />
{dl S~~e of p?S f .DOSUre M+fon+utan on dttdlsood<br />
taposutes from a fether, mothtr, and other hosnehotd<br />
enemben end adult e.posuret from hutb+rdlsl, t>tdser<br />
household memben . and occvy4tran+l end nocul ae .<br />
esMV 'r oblorned br quetironrur+t The riti <strong>ets</strong>oc+sted<br />
vnth nposurt to 1rTS from dd(ennr tewrca enE iuusR<br />
dd(erent time perrod, ean be tv .tuaud<br />
fe! Confoundtn and C)ther Rnt rKton Rtuwe the<br />
ru=nwude of the m+tn ETS tlleet rt etpttud to be veu11 .<br />
h rr iMponlnt 7o tltt rntolctov'Ir porentylcOnfoVndtnj<br />
tanorc and t(feci mod,rY,nt 411111 sn , pudy w-+th a<br />
wfhcnnlly farte number ot eetts end eOnuols h et<br />
ttnhcrpated that upon complelwn of thrs ttudy ebout fA0<br />
utes and twrce th4t ewmbei o( controh wiA have<br />
p&nrctp+ted<br />
Thrs rtpon reprerents frndutp fro+n Nx c>rsWn ;<br />
t ;tudy and Mx(udet the Lrtett nurnber of fr/etrmt non•<br />
tmolt't vrfth iunS tencert repaned to date Thn report<br />
wit (th to ba tuttified {-ventht public htttth wnpon .nce<br />
of the tfsue under m,tsi,}ttron<br />
I<br />
Methods<br />
The s,udr is e popu4rion•based cese-conrrol ttudy of<br />
tune c .ncer rn .wor*en who ha .t ne~er t»ed .nT tobacco<br />
prodvrt This prr6enrv-y trpon rnctudes eeses du=•<br />
nosed dur,nl the hru three rer*t (Decemtxr t, 11d5<br />
Ihrou'^ December 31, I9S6, ol a S-yar ttudy At the<br />
rme o( d4) .+os s uses wert residems of one of (rvt<br />
nujor rnerropoLUn areis rhrouthout the tJnned Sutes<br />
(nclud^g Atlanta (CLt'ton Cobb Dea.tb Fuhon, and<br />
Gwrnnt'I countr
)IV~ r VaV'~ iM+~eKNt~+~M ~.~ w w
somommammmazzo<br />
as a, . ., t,.W r NON- ::k;,<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
a.*<br />
ou. e .~ e. & .!a rrer .., ...M+w ',<br />
Aome i Tmuhs or mae du+ini chWhood ChfldhoorJ<br />
tivas defwd as thr iru 11 rears .rlie Eaye»ur$t (rom<br />
parents after ehit t1me , .." cia»,f,e•d as other M,w<strong>ets</strong>old<br />
mtmbers dunnj ad .,h ldt Dichotomous ETS e :powrn<br />
wtrt firtt tUmrnad Itvtr rY Re+Trl bt type of tobaccoo<br />
craarettes p'pr c,la•, or any of tMst tyqes of tobacto<br />
pose w+s est'mared at approprure by M++emrry /t ` .<br />
numbtr of crg+rrnes/darl, duurwn (e t, numbe, of<br />
ynrs e .posrd' or a comb-nat,an it 1, pack•y .arnl Pack•<br />
Ytt'n of ti{erette e .posure trom cht spouu arrt ca9cu•<br />
l4rtd by mulr'ply,nl the numbtr of packr unolced ptr<br />
dar b1 rht number of yte .rs the i.po%ne tenoktd e11arrnn<br />
wfi,k 4vrni ~,,h tht ttudy subttrt rack•yeers of tapKture<br />
wtrt eummed (or all r,nwk,ni tpouses of eaCh tWdr<br />
wbttcf<br />
Ont of the obtec+rvrs of thn etudy was to r-vaiwte<br />
the essoc,ar,on of ETS with sptcifK hmopa+holo`icel cel+<br />
types of fun& <strong>cancer</strong> 7he altwrd dntrrbutron of hatopatholog'cal<br />
trpes prec)uded anis, mtanrntfuf ana)tsn by<br />
tpe0 .c cell type orht, thin adenocaremoma arnd all<br />
orher ceP sypt, comb~ned The reaults are presented /or<br />
+11 (unb <strong>cancer</strong>s tomb,ned In .. 420I .nd adenoc .*cmomas<br />
cont,rmtd by 1+lstope's+ofog~cal reYreM (n . ={1) .<br />
Cates wtre cornprtd so each control lroup wnh<br />
re`ard to the d,vrrrbyt,on of rrle .ani co>aruur such as<br />
aIt educat,on sncomt ar,d race/tthn~crtr The aswcr•<br />
at,on of ETS tapoture w~th IUnti <strong>cancer</strong> rnk was dr ..estr<br />
P+td Lrst rn eont,ngeneis ubks ttratrLtd by dnrfn oe<br />
ump!mg .arables la`t, ract, u,.dr etnter) and eilevant<br />
co .ar,ates Sumrna•y adsusted odds ratw+ and tett euus•<br />
hcs v,ert caku4ied bt the mtthod of rvtantef and r4en .<br />
sre) t)J) Uncond,t,orul tog,stuc rta-tss,orn analy>•n yrrtre<br />
then used to ettmn+se the attocut,om by nummary ad•<br />
jutted odds ratros, eonfrdtnce hrnns . and (nt wxrusei<br />
q7 .14) .<br />
te.arftt<br />
DemoSraphic tharacneristrn !+t tasr+ and eewuroh are<br />
presenttd in Table 4 Casts and eontrols wert u+nitar<br />
evrth tnpen 6o matth,ns varubles and tnoel ieerw•<br />
1 raphK wr,abtes The larlest ewmbt+ of ta6n in • 1tiQ<br />
1141 were rts+dentt of tos Arqrln, Ootto-td Ivr eAetc<br />
lrom ttu San irancnto sar Nta !n . 149, )S!k) . and<br />
then the three t.mat(er Nudy centers h the southtrn<br />
Unrted Statn AtLnta tn . ai, 1 t161 ; Moutton (n r»,<br />
p•ti), and New Oritant /n r=i . trx1 .<br />
The a=e d,st,ibution of tases arsd tonwoSs ts exvfoeen,<br />
wnh f) to 74% of tach .erKS betwten the ain of Lo<br />
ihrouo !1 The proponbn of otdtr .romen ws thsu {rovp<br />
of fenute norumalen whh kml unttr 1t hsher thtn<br />
...____._-.<br />
w.. .r «r+~~<br />
r» e,,., t.+<br />
rN M~ i. rwr, .' ~t".u` mf r.w~. t+e~9*~<br />
-<br />
thai antonl •A kr+,ak kRy cantrr cyu1 t't the SEER<br />
irofram W4-1!!6, en wb+ch tanty 43% Mt eht Cases<br />
were aRtd iS or esidtr E)S1 .<br />
Cases tended to have a>,oR .ewfut Iorm isouse~d<br />
1 .co+ne an$ kss eduut on than the popuUtwn tontro{s<br />
P,tp a .,rnattY~ D51t, of castt$ tnd conrrob Upen+ t#een<br />
rf. :tiood m crt,es wr>h poputatrons of 50 OOC or tnae<br />
and rnt enatornY of uses and tontrolt f70% i8% ,17f+<br />
for ta<strong>ets</strong> Colorr Cancer conr,ols and populas,e,+, cor+troo .<br />
tetptctrr2ly) rnrded en CArn durdy r+rasr of tM•r aduh<br />
Mft . The ntrnuttd r:sks of IvnS unctr In no+srnoArtq<br />
women astocattd w9h gve, hav,n` Ir .t•d wnh a ~t<br />
who tmoked are plestrtited .+Tabk S The adtusttd Olls<br />
and tht 1S'r. Ct are verr e+m,tar (or en tpoutio-ralaud<br />
eepo+ures reEardkss of controt Sroup for ali h,srotyth•<br />
olo{,csl tyrpes of )und tance comb,ned a 10', . srycrtau<br />
r, rrsk rs obur.3d lOt . 1•SI and 1,Y4 wnh coko++ea+_et<br />
and populat,on tontrotst For tath of tht thrte rvpt, of<br />
tobacco trrsaled the ORs ranged from 1 14 to 1,36<br />
When thr case ser,ts rs tetrrtoed to the Sit ®ulrnorteR<br />
adenocarca+omas conr,rmed bv h t+opa+t oto= ca~ n .+t . .<br />
the ast•acur,on it mort pronounced Appro .,marNr Sa%<br />
ekvat+ans m rnl of adenocartrnor?,as of tht Ivn= 1t s<br />
p OS1are assocured wrtt•.anr s»p ar tabacco by tpoustts) .<br />
and cla,ettt smolinj accounts for n+ost of the tobacco<br />
vu The ewnuted rt4t, .t rnk of pufmawh ad+noctr•<br />
t,nomi associated .smh tr`a,ttte tnnoLms by eto'uttr<br />
was 1•)i 1142•1 .N1 W+th tht poputtitron tontrois as<br />
comparrton and 1 .31 (0 }e .1 1 .t1 wnh she cobn carce+<br />
tonnolsascomparM1On No~ettotUl,onbtlweMtpOUi4f'<br />
lobacco vst and bunf eancen oahe, than adrnocrcr<br />
rr,rru tsquamous tetl . M>+tI tei!, ierse cell, and other ; Fit<br />
. ~/I was observed . '<br />
Sepa,att ana)nn .rtrt tonduc+ed cor wbtent .Mto<br />
prr .onallt rtspondtd and So+ whtm mtornyt,on a+ys<br />
obumed (som eurolate rnp"ents The tadds satrot tyr<br />
involuntary tapotute to ET5 were very oreni{ar fot droth<br />
groups of tespondtnts ; thtrefore, the eetuhs set noe<br />
presensed in the ubtts etparate)r by trp* ol neaondrru-<br />
Orne such tumpk 11 tht ty1,RUted tetalwt rnk of e++onary adenoca ctnorvs a+wcuted wrth erp*tnt<br />
vnol,na by tht spouu OR . 1 .18 and 11 .110 to+ eunoµte<br />
and reif•rtrponden7l, Ieropectn,tlY, tompar,na use+ eo<br />
eofon Canctr eoetirph .<br />
tffedts by ttsrdr tenttr wert at .o t .amrntd Yke<br />
odds rafros bY censer ranled froM a bw of 1 .17 to a hrit,<br />
of S i4 to, rnl of pulmonart adenocarunoma assoeetttK! ~<br />
with tpc,usn'tiL arnu .mok,nl drreust of the kmntd ~<br />
6ampk wn . nona of N .e rnd,vrd"l suudv eentet aqt .• ~ .+<br />
N<br />
~<br />
~<br />
Jot<br />
~<br />
~<br />
0.114
tYa'4 QMNy.nN s, LH( cMC . tM M6 rlwY RfllWle r<br />
a . .c,.e M'Mi'tv^c rwu .ww'r,<br />
~ C«r<br />
i.~co. Bx~<br />
u.rt evnh<br />
en • 3a0~ r^ • 3Sti<br />
r.<br />
INv.+tr .~<br />
eo-l.n<br />
« • 7•0,<br />
A~ w ftr<br />
immi, c~<br />
Alr.n,<br />
K /tt* M /1J31 )r et f i<br />
lanre.•<br />
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enates vsrt tutnrtca8r /if n,ftcant . •nd shey sAd no( V4•<br />
niLuntly d'iltr Gom orse anWhn .<br />
is+mam of rt4tivt risl •swcuted .r+th thr nvmber<br />
of cisa'ellet smoled by 4 spauu wefe /ynAtcantfy, tittroted<br />
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c~ renrtpddsr : 2 .06 (1 .N•) IFltand 141112i•2l11bt<br />
adenocerctnoml o/ sht hxti comp+rrn uses lo ir,bn<br />
cJncer tnd popu4lwn con/toll r»penNtly pdds ra+tos<br />
wert am,i+r, ahhou>ih aJ1)hllt iower . Io, atl (ypes ot kmS<br />
taae+ comb~ 1 .7011A7 •1,ta) Ind 1 .M /0 f0•2 .0b1<br />
Ofac1•yelrs .rrt tumrnrd at a ceNS+brntd t}wvwre<br />
Irf duratron and doa of eapo .ure to t1,t husb+n4 s csy•<br />
rrne t+noktnl The odds ralat la an cen types el prnj<br />
pncer comb,ned and (a •denocarco+ema o/ the iun)<br />
Ke drsp4ytd m iq 1, Separ+rt anatysh trert canduned<br />
wnh each conarot roup fa canp+nson . I+cauu Nx<br />
Fndtnjl wtse t,0 b+en+4 br •Kh jrp)p the Kyt/ks art<br />
ptesenttd (o, tht ttw contrd •efKS tombttsed fn .<br />
11)11 An ncrtas,nl rnl of tunl tlnce+ and aderwcarc,•<br />
ttoma of tht lun` nwculyd .rnh an rscrtasrr4 Mrr1 ot<br />
tepcsu+e to the tpouu's epl+reue Imoltna evas ksxad<br />
The posn,+a Irtnd n nsi by psrl•y .an o/ tVo"t a<br />
µttrst-clh, u{n,(K1n1 kr adtnoc .rcw+ortu of th+ du+tg tr<br />
t O Ot) / "elrr dou rrspome • tsbtierred w4~rn all<br />
Iuslopathotot cN typrs o! {vey carxer art eombmed<br />
pttnd ~ • 0 .071 .<br />
Eapd+vyt 1o fTS hom ranous wwcet tlunq aduh<br />
ik wts evafw+ed The resuhs ut wmrturaed sn Tab4<br />
• for t•rmpl,cnt of Drt+enul o+, the 4a11 m ttw table<br />
•ts0 tepresenl the t,nd,ngs usmg the t .0 control roups<br />
eomb"ned becauu the tndwtduai re+uhs usmS eK1, ton•<br />
erott aup .trt ent rely cor»atenl ERpossxrs so eopp<strong>ets</strong>e<br />
ImolInI lrom syoustltl . olhtr hou+rhold men,ben, on<br />
!ht pb and ,n ather aclrvnel o+ aduh l,+t thocaarr ste<br />
trach assocuted wsh an over.ll 10-60ti% y qqrttcanl rk. .<br />
vatwn sn Ihe r»1 of adenoc .rc,nwru ol !hs h+rs2 /u<br />
ewted prr.~oustr ta tpavu•rt4led tipo+vret the eak<br />
p,I+Mlet to, all lun` ceMe't .hti0ut rfjArd lo cell t1-pe<br />
ltnd to bt ilthti, bwrr sh .n the tompirable t+tmutrr<br />
/a •denocarc«nonu of the hmt inntlKanl yasene<br />
utnds il c 0 05) sn rul oi adtnocarctrwtn+ bl tht 4md<br />
"re •ssocuted .rth rncreannq durlt,on tyearsi o( et•<br />
"urt to ctj.wte smole hom a Ipoure . Wher 1vw+r•<br />
hold members and wcul ocratrons fot aduh hovsrAold<br />
ttiposurts (IOR1 1 spouse and othrts Opsrrmates eN tssl<br />
tose hom b. .ett 10 h,1hesl r+ Ihe 30 a rnae .+t» ol<br />
t .posure cale•loh, hoWr .er, stends wtre not >,rnoaih {w<br />
taposuret m occuptt on+l Ind wcul unsrs#s<br />
No assocutan s.1t tound be+aeen rtsk ot an, tvpc<br />
of lun2 c+ncer and childhood taposute to tsjan .'aptt, e>i+'ettel<br />
. or all irpes of lobxco comblned lable 7<br />
p+esents the estirwttQ se4t,vt mks or lun` eaPrct, and<br />
adrnacarr,nonu o/ Ihe luna amons narnmoltey sbnsrn<br />
whose /11her, ossother, os orhtt househo3d Rsember<br />
/molItd duttna childhood None d,lleted •r{ndKamll<br />
kom un+rr• t'etn ottaposufe end amaurU snu>atd .*,e<br />
also tumined No i.I2n'tKam ek .Ittom tn txa wf"a<br />
four.d at anT krel of Imol,n4 br hovwhold +armbers<br />
"ft ch,ldhood .<br />
ditl'1RfiM<br />
One ®f tht mosl plslm ; Gndrkjt of ehis etuds a H+e<br />
`ntribulson of ahe hittopaholopcal eell erpts of krrs;<br />
tyncer an a pbDu4lan•batd lertes ot u3t•s a11<br />
Klttned lo dtletm,ne Wkt,mr vtoMmoler Otalus irv•<br />
Rntr-t,/ht % o{ )5f re--r .•td tL`ible cates snlhn retoa<br />
.~ete c4lurKdas aarnocalc~nomat Th,s h}h p+opcvtasr<br />
ef adrnocacusomas and the p•rurny ot lo,,amcnn ind<br />
/ntatl eell cactnomat .at tBM,t1H,l arrens AA MWly<br />
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centen M the etudt 01 Kibet .nd Wyflder W, a timiL,<br />
propon,on l74'. .i o+ Krevberj It trpe turnoh wJs fov+sd<br />
in thea wrxl ol 9' non/rrtoi,ng rtrru/es who+e /eIi•<br />
reponed nonfmoLmg S71tus rts con6tmed by than r!•<br />
.+e». In the U^ted Sutet .denourcmom+ n the most<br />
tommon hntot>a+holo~ al Cen type o( Pt+mi-y iunt c•n•<br />
eer m women bu+ fhe proponion oi tll /envte iunj<br />
etncer uset wtth il; subrvpet o+ edenocerc,noRUS (pJp•<br />
illrn . tnru bronch o~ai~eorJ+, tnd ta4di n}a'w tSEFt<br />
Publtc U .er Ttpe 117i• tl17t<br />
Ouf l+ud, rn whicA tdenoctrc+nOrru n prttiannunt<br />
and rs tt,e cell sype ckut . awc4led r,u, wecreo .ed eMl<br />
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Orce, w .+Ye .DOf .Q asre.cae.nr t.wr/et•f rdt<br />
trom .duh ITS eajmurei n te+ comrtst ro rererai et! Me<br />
•tri,er ttudKy o( se,,.olunuh t :pau+e to ET5 Tnchw<br />
poubs et tl 12) m the mny/ ct/e•comrol etudy o+ hP4<br />
ttnce+ tnd passivt tmolmI .monA rarnn+olml won,tn<br />
tsctuded uses o( adenat+cmorru mclud,nl bronch+oiwl,eo(V,<br />
however, thtt ttudy K+ciuded r,o histop+thobf,ctl<br />
tevK . Thet rcponed tn Dddt (tt a hom 1 .1 to<br />
) A tewcu+ed +vtth the husbtnd / fub+ts Di6•<br />
ser tt Jl 1141 rtponed t)•told ekrtled nsd astoented<br />
Wlth the {pouSe I 1mG!
1W t ..st~~e+Irr+ ..e~ r .r .~ 4•t crrr rO .r .+ esp.+~n<br />
a cw+'a~. swe.r / .ary a+~nsnx .~w•<br />
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142 4 V • : o•,<br />
>be 130Ce3•510, t3'De]•24),<br />
ore.w r .sia t«.W r .oto<br />
i.r .+ ess.u-r<br />
0, .•euuw6' t3lrt .l)•2o+r t{o 1 114• : t i r<br />
0 /00 tOc<br />
1 .1s t)+ar .ta, )2" an•te1,<br />
ta)o rotr,)t•),tr 2 6onii-)b,<br />
>IC tesr0u•JOOl tsos0 :a• . ."i<br />
t ..+,or .oaocti<br />
t . .•se•oac :<br />
' Nir+~.~t w' Mr utr siAr ~~ .~ frnr.w~ srrne IV N~cMis~+<br />
'1lOM<br />
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" i+c a' .arn r a w' .w ar t vw .+ « J .• wa .r s•h. .+s *r.<br />
w-r/h VhP tM+ KtA++w' Md irw*de wr'V .•r rrwM~<br />
ttr.+.e<br />
'1t0At<br />
veaiL+ utcinoma, comprised 46 1% of the total knuk<br />
nons+ a} nc ustc 1n the Swed,sh ttudy o( ftrshaitn rt<br />
at 13i1. 57'ro of 77 ttmtie nonsma4en wtrt adenocu•<br />
cmomat and 31% tAu{mous .nd tnutt cetc urcrnorrwl .<br />
The only suoaticlfiy /tjnifKam TtS•atsocuted a.crtastd<br />
tisk was tot Iquamous and artull celi cetca+o++us, the tefl<br />
types with she hr=hts+ rotat„n risks assocrated wtth annt<br />
vnoklnj At the prtsent trmt +rnaif numbert Of /qwerasn<br />
ctn and t•nuil cN( c.rcnwm+s tn ow dau set prttiude<br />
an adtquett t+tstlsment of tisk aISacuted with [TS t>
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prAn lir,.a.r/ .r .rl .~ US tu tpt<br />
~ A{MrM W Kr IK 1 YA . r>ti1 IM•rr K'M" . arY rf•fiow<br />
• CAifti .M . Mwe r/rV 11 wr+ M Yw<br />
dur•tron In comb,rwt on may Y.tfd rrwn mtlanin{fuf d,i•<br />
ferences rn e+po+utt than Ihit meetured by duratbon<br />
alone The rncluuon of nules m the New York Nudr,<br />
with poss,biv bwer douy oi ETS t .posure from tmokrn{<br />
wwts fo, (t+•e! ytjn and dunn{ a more recent aR+e<br />
peood mat h.ve reduced +he reUr+ve rrsk nt rrules tlut<br />
were not ;ender tpecdre A pudy /n nonheast Chw,<br />
whrch . 81 cornpirable in $12t to our study Ktuatly<br />
found • decreesed rnk o+ lun{ <strong>cancer</strong> usocuted wrth<br />
E15 etpotures rrom spouset +nd rt tuiSest, .e r,c+eatt•ed<br />
rrsk essocyted wdh pt+er+ul smokmE (40I Aj /,ug ;esred<br />
b, the authort, theye women had heivt eaposurts to<br />
both mdoor and outdoor poflutantt . Minrch met ha`•e<br />
obscured anv e(tect of ETS .<br />
Thr stud,es which ha,•t tun+r»rd rh,tdhood rapa<br />
eufes •,t more Irmned then those wh,ch !uw (ocusrd<br />
on tobacco use b~ /pou+el and thr over1,11 findrnts are<br />
inconclutrvt I), S, 11 .14, 22 411 5+ud,rs o/ 1he relyb,hty<br />
of recsN of ETS e :potures w{Eest thet reuU of a petenrs<br />
/mokrnE hu+orr n kss rel,ib4 thjn thit lot tpousts 1)1<br />
)9i and this rru~ account'T, p•rn (or Incomntencrts<br />
berween stud,tt Nnerrch n al f22i (ound e )•sofd In•<br />
crttsed rnl atwcurtd with =S a nwre Imoktr•wars<br />
durinl chJdhood rtnd adokscence but rw /ncrtau for<br />
chiIdhood e+powre+ ot ksl than 2S smoker•reaus IOR<br />
. 1 09I In most ttud,rs which have reponed posrtwe<br />
alsocNt ons, the fmdm{s hive bern prirturrfy for eyttr•<br />
rul E1S ecposu,ts m smol,ers rather th .n m rwntmoken<br />
Conei ti at, (Sf found a .qndrunt(y u+cre•r•td nik pf<br />
lunE unter IOR • 1•)i1 among /moken whotit Irlp(her<br />
emoked but no incree .ed rnk m nonsmok.en and elo<br />
ekvited r,sk assocuud with the u+her'/ t.mol,n` Wu el<br />
J!. ttti reporned a nontr`nd,ctntly ekveted msk o( ade<br />
nocircinor>•u of the lunj fOR a 11) in knules, W% of<br />
wham hid a history of smoking Srmit .rly• in a Swrdnh<br />
tuudy of (ern+lt 6un{ <strong>cancer</strong> whlch inc{udtd jecimln+oke du}ml .duh hfe erom a<br />
s•trtty Or tLpoSUtt •o6rrcet The a1t•oCYi,on wa1 i4e'cffK<br />
fo, kat1, adenocarcrnoma ot Mt krnll •nd /or atl (unj<br />
uncen comb•ned compared to colot, eancer<br />
Ac{no .{t1,ww*ti<br />
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l.y .W w Mw w.. u,I, r/0 . PM ww Ar- lk,.r+w• wM e.rM<br />
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1 . C•,,, y ., .., .u•J,ws 1.on.• .M b .y . i.•w w ra'4 `y+-<br />
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4
Garfinkel, L . Auerbach, 0 ., and Joubert, L ., "Involuntary Smoking<br />
and Lung Cancer : A Case-Control Study," Journal of the National<br />
Cancer Institute 75(3) : 463-469, 1985 .<br />
Another U .S . study, by Garfinkel and colleagues, is a<br />
case-control study of hospitalized women in New Jersey and Ohio,<br />
published in 1985 . It includes the following estimation of<br />
workplace <strong>exposure</strong> to ETS :<br />
The interviewer also asked about the average<br />
number of hours a day the woman had been<br />
exposed to the smoke of others at any time<br />
during the past five years, during the past 25<br />
years at home, while at work . . .<br />
The authors report the following :<br />
[The] OR for <strong>exposure</strong> at work during the last<br />
five years was 0 .88 [95% CI 0 .66-1 .18 ; 14<br />
cases, 52 controls] ; for the last 25 years, it<br />
was 0 .93 [95% CI 0 .73-1 .18 ; 34 cases, 118<br />
controls] .<br />
These two point estimates represent negative associations between<br />
reported ETS <strong>exposure</strong>s in the workplace and <strong>lung</strong> <strong>cancer</strong> in<br />
nonsmokers .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
Involuntary Srnoking and Lung Cancer : A Case-Control Study'<br />
L.vnnncs Qarf)nktl,2 Oncar Auarbach,z and Lou Joub*rtz'<br />
1.OSTqACT-In a casa-control study in A hospitals from 1671 to<br />
ta8`, taf cases of lunp <strong>cancer</strong> snd 402 tusas ol colon-rrctum<br />
qncar (the Gontrolsi w+re /Csnfifwd tn nonamoktnp woman AII<br />
casns and controls w.rs confvrr> .d by htstoloqic ryrvhw of ftio",<br />
and nonsmokinp status and axpoaurss wars wrnfs.d by sntsrrs.w<br />
Odds nt os (OR) sncnasrd with Incr .as,np numb .r of ciparanrs<br />
smoltso by the husband parttcutarly for cipanttss smokso at<br />
horna 't•na OR for wom4n whose huabandt tmohsd 20 or mora<br />
oiparnnas tt home was 2 tl (45ti4 contid.nca hmm t 13 . 3 .95) A<br />
ioqtsttc nsqrasa,on anatysn anow.d a significant poa+Uw trsnd of<br />
tncraas+np risk with incr.asQd .xpoaura to the husbands srnokiny<br />
at hCme contr0l}10 for age hospital soQioeconomic claas and<br />
y.ar of oiaqnovs Comparison of women class1l,rc1 by numper of<br />
hours Utposed a day to smo>
,<br />
481 ()rrflnk .l, Auarbaoh, and Joub+ri<br />
verification of the smoking history ln a study of the<br />
histologic type of <strong>lung</strong> <strong>cancer</strong> in relation to asbestos<br />
<strong>exposure</strong>, 49 of 774 men and women with a discharge<br />
diagnosis of miaoscopically proved <strong>lung</strong> <strong>cancer</strong> were<br />
rccorded as nonsmokers in the hospital chart (10) . After<br />
review of hospital records, histologic sections, and<br />
interviews, only 10 nses retnatned who had died of<br />
primarv <strong>lung</strong> <strong>cancer</strong> and who had never smoked . One•<br />
half of the others had smoked at some time and, one•half<br />
the confirmed nonsmokers had a primary <strong>cancer</strong> other<br />
than that of the <strong>lung</strong> .<br />
lt is apparent, therefore, that more studies on involuntary<br />
smoking are needed, with parttcular attention<br />
giver, to obtaining microscopic proof of primary <strong>lung</strong><br />
<strong>cancer</strong> and more detailed information about <strong>exposure</strong>s to<br />
cigarette smoke,<br />
METHODS<br />
To have available enough subjects for a case-control<br />
study of involuntary smoking• we obtained access to the<br />
records of 4 hospitals-5 in New Jersey and I in Ohio . In<br />
each of these institutions, we identified all <strong>lung</strong> <strong>cancer</strong><br />
cases in women recorded during 1971-81 . In 2 hospitals<br />
the cases were selected from the Tumor Registry ; in 1<br />
hospital, they were selected from the surgical index in the<br />
pathology department~, and in the other hospitals, records<br />
from the pathology laboratory were checked against the<br />
medical records diagnostic discharge index No case was<br />
selected that had been diagnosed prior to 1971, Cases with<br />
<strong>cancer</strong> of the colon-rectum served as controls Colonrectum<br />
<strong>cancer</strong>s have been shown in epidemiologic studies<br />
not to be related to cigarette smoking Charts then were<br />
located and reviewed Cases that were diagnosed clinically<br />
only or by cytology, or as sarcoma or lymphoma of the<br />
<strong>lung</strong>, were excluded Those that occurred in smokers (or<br />
ex-smokers), according to hospital records, also were set<br />
aside . Only those charts in which the patient was<br />
specified as a nonsmoker, or in which the smoking habit<br />
was not recorded, were further investigated .<br />
All the slides for these cases and controls were pulled<br />
from the files (an average of -15 slides/case) and were<br />
reviewed blind (by O . A .) . In a small sample, slides for<br />
cases and controls were reviewed a second time to check<br />
consistency of the findings . Another sample of slides for<br />
smokers with <strong>lung</strong> <strong>cancer</strong>, and for subjects with diagnoses<br />
of sites other than <strong>lung</strong> or colon-rectum, also were<br />
selected for histologic review and were mixed in with<br />
the slides of nonsmokers . If slides were missing or not<br />
available, or of too poor quality for accurate diagnosis,<br />
the blocks for the case were located and new slides were<br />
prepared<br />
An interview based on a standard questionnaire was<br />
obtained for all cases and controls, along with microscopic<br />
proof . The interview was with the woman if she<br />
were still alive or with next of kin if she had died .<br />
Seven interviewers did all the questioning, three did<br />
interviewing in all 4 hospitals . About three-quarters<br />
of the interviews were with the patient or with spouu<br />
or children . All other informants had known the sub .<br />
JNCI VOL 75, NO S . SErTEMI
TABLE 1 .-Lui19 caM1ffl ill HTOflKti u•ho nn~r* nnokrd<br />
Recordr of 4 AotPUL• 197J-a1<br />
Status<br />
No of women examined<br />
At hoapials-<br />
A B C D<br />
Total %<br />
ldtcro.
4" Garilnk .l, Autrrbach, and Joub.rt<br />
Variable<br />
No, of easa<br />
No, of mntrols<br />
OR'<br />
}5t CL<br />
TAltl 5-STMOkr rrpoavse beJon tuwp cowcCr dio.pn.o.u . os elasriJud by hYaband'i smoking k&bvL<br />
N one'<br />
43<br />
148<br />
1 .00<br />
N one '<br />
Husband's touW smoking habits<br />
Cisarettesiday Cigar and/ All typts<br />
Specification<br />
"$ f3arifnkel, Auerbach, and Joub .ri<br />
a1SCUSS(ON<br />
In a previous paper (4) the problem of classifying<br />
involuntar . smoking on the basis of the hus,band's<br />
smoking habit was discussed It was pointed out that<br />
questions directed at ascertaining a quantitative estimate<br />
of the number of hours a day that subjects were exposed<br />
might be a better measure than the total number of<br />
cigarettes that the husband smoked, inasmuch as not all<br />
of the husband's smoking was done at home . In the<br />
present study we classified the <strong>exposure</strong> both ways : by the<br />
number of hours per day the subjects were exposed to<br />
smoke of others and by the husband's smoking habits .<br />
We also recorded the respondent's estimate of how many<br />
cigarettes a day the husband smoked at homeIn this<br />
`ioup of women, husbands who smoked cigarettes<br />
smoked an average of 27 cigarettes a day, of which 11 .5<br />
cigarettes on average (M) were smoked at home . Of<br />
course, all cigarettes smoked at home were not necessarily<br />
smoked in a room where the sub)ect could have been<br />
exposed, In this study, the husband's smoking at home<br />
was related to the women's <strong>lung</strong> <strong>cancer</strong>, whereas number<br />
of hours of <strong>exposure</strong> a day to all sources of tobacco smoke<br />
was not related .<br />
A potential source of error was the hospital's report of<br />
whether the subject smoked or not, In this stud), 40% of<br />
the women with <strong>lung</strong> <strong>cancer</strong>, classified as nonsmokers (or<br />
smoking not stated) on the hospital record, were smokers<br />
at some time (table 1) . Another 13% did not have primary<br />
<strong>lung</strong> <strong>cancer</strong> It is apparent, therefore, that in any study of<br />
involuntary inhalatton and <strong>lung</strong> <strong>cancer</strong>, the smoking<br />
histories of the subjects have to be confirmed as well as<br />
the extent of their involuntary <strong>exposure</strong>s Smoking<br />
histories of husbands were obtained for the 113 women<br />
who were smokers The distribution by smoking habit is<br />
shown in table 9 . As we might have expected, smokers are<br />
more likely to be married to smokers than are non•<br />
smokers The table shows that 43 of 134 women, or 32 1%,<br />
of the cases included as never smoked in this study had<br />
husbands who never smoked ; but only 21 of 113, or 18 6% .<br />
of women who smoked and were mistakenly classified as<br />
nonsmokers in the hospital record had husbands who did<br />
not smoke . Among the controls only 8 .5% of women who<br />
were called nonsmokers (or smoking was not stated) were<br />
smokers<br />
The table shows the effect on the OR, when one<br />
assumes that 8 .5% of the additiorul controls needed for<br />
the 1 :3 match had husbands with the same smoking<br />
distribution as the husbands of cases who were smokers,<br />
and that the balance had the same distribution as that of<br />
the 402 controls included in the study . The OR (or the<br />
husband's smoking increase to 1 .61 overall and are as<br />
high as 1 .63 for the 20-59 cigarette a day smokers and 2 .32<br />
for the women whose husbands smoked 40 or more<br />
cigarettes a day . For <strong>exposure</strong> to the husband's smoke at<br />
home, the OR are 1 .66 overall, 1 .53 for women whose<br />
husbands smoke 10-19 cigarettes a day, and 2 .85 for those<br />
whose husbands smoke 20 or more a dny at home Thus<br />
the inclusion of women whose smoking habits have not<br />
been reviewed greatly increases the OR .<br />
TABLE 9 .-Nypot)ttical OR resvltinp from rombininp wrom .tn in etudy u•itA women oripinally ctassiJud<br />
oy Kotttmoktrs but u•ho actaally smoked<br />
Husband's toul smoking hsbiu<br />
Variable Ci`arettes; day Cigar All Touls<br />
None<br />
endr or<br />
types of<br />
< 20 20 39 Z40<br />
pipe<br />
smoking<br />
No of cues<br />
Nonsmokers (in study) 43 11 82 30 18 91 134<br />
Smokers (originally called nonsmokers) 21 9 43 24 16 92 113<br />
Total (untcreened) 64 20 75 64 84 163 247<br />
No . of controls<br />
Nonsmokers (in study) 148 45 102 52 55 254 402<br />
Additional controls' 119 88 90 45 47 220 339<br />
Total (unureened) 167 63 192 97 102 474 741<br />
OR 1 .00 1 .01 1 .63 2 .32 1 .39 1 .61<br />
None<br />
Htuband's smoking habits at home<br />
Civarettu/day Cir .r All Totals<br />
l<br />
The classifiation used in this study might be criticized<br />
because some women married to ex•smokers could be<br />
counted in the same <strong>exposure</strong> ategory as a woman<br />
exposed to smoke up to the time of he~ftnal illness .<br />
However, all patients who have gone through diagnosis<br />
and rcreatment for <strong>lung</strong> <strong>cancer</strong> had some period of time<br />
when they were not exposed to others' smoke, either<br />
before or after treatment . We believe that the classification<br />
we used was indicative of the "usual amount of<br />
smobce to which the person was exposed ." To determine<br />
the i:xperience of a"pure" nonexpoud group, 17 cases<br />
and 56 controls in this study were identified who were not<br />
expcned to the smoke of others during the last 5 years,<br />
during the last 25 years, whose husbands never smoked at<br />
home or elsewhere, and who never were exposed to smoke<br />
in Kheir ehildhood . These cases and controls were<br />
eompared with all other subjects The OR was 1 14 (CL :<br />
0 .81 . 1 .59) .<br />
In conclusion, we found an elevated risk of <strong>lung</strong><br />
<strong>cancer</strong>, ranging from 13 to 91%, in women exposed to the<br />
smoke of others, although the increase was not statis•<br />
ticall% significant . The women who were married to<br />
smokers of 40 or more cigarettes a dav or who were<br />
exposed to the smoke of at least 20 cigarettes a day at<br />
horne showed a risk twice as high as that of women not<br />
exposed at all . This result is consistent with the dose•<br />
response risk of <strong>exposure</strong> to the husband's smoke shown<br />
in some case-control studies (2, 3). A dose-response<br />
reLationship was confirmed in a logistic regression<br />
analvsEs . The lack of a relationship when <strong>exposure</strong> was<br />
classified b% hours exposed to smoke of others map hale<br />
occurred because this variable does not accurately mea•<br />
sure intensity of <strong>exposure</strong> . There is no consistently<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Inrolunt4ry lrrnoklnq and Lu" Cancor A4g<br />
higher risk for certain age groups or by histologic types,<br />
or by <strong>exposure</strong> at home or at work Exposure in other<br />
areas carried a higher OR, but this finding is difficult to<br />
interpret<br />
!lEFEiiENCEB<br />
(1) HIRAYA4A T . Non•unokmg wives of haw smokers havc a high<br />
mk ot <strong>lung</strong> c .tuer A suudy from Japan !t Med J 1981 .<br />
!>32 1 e s-185<br />
(?) TR>anroE•t.0s D . KAUN-nstr A . SrAaRns LL ct al . Lung <strong>cancer</strong><br />
and pasttve smoking int J Cancer 1961 . 21 :1-4<br />
(1) CoRREA P . FoN7HAw E . rIOCEl CW, in ut Passive unoktnR and<br />
<strong>lung</strong> anar Lancer 1963, 2:59i-597<br />
(I) GARrtwuL L. Time urmdi in IunS <strong>cancer</strong> morutity among<br />
nonsmokers and a nou on pautve amoktn` JNCI 1981, 66<br />
1061-1066<br />
(S) DLAIAT GG. WYNDtR EL Lung eaneer in nonunoken . Cancer<br />
1964, 5! 1214-1221<br />
t4i SANoLta DP .EvtRsoN R6 wtuox AJ Pasuvestrsokrn6rnadult•<br />
hood and ancer nsk Am J Eptdemtol 196$ 121 .37-48<br />
(7) CH1r. WC, Fvr.c SC . Lung <strong>cancer</strong> in nonsmokers in Hong Kong<br />
ln Grundmann E, ed t,.ancer campaign Vol 6 Cancer<br />
eptdemtologN Stuttsart and tier, York Flscher VerlaE . 1982<br />
199-202<br />
tdl Koo LC . Ho JH .C . SAV, D Active and passive smoking among<br />
Irmale <strong>lung</strong> nncer patients and controls in Hong Kong J Exp<br />
Clin Cancer Res 19A3 4 .l6i-375 .<br />
(91 FRIED40, GD PrTTtTI D9 6w,ot RD PretalenceRndcarTelatei<br />
of passive smoJ
Janerich, D ., Thompson, W .D . Varela, L .R ., Greenwald, P ., Chorost,<br />
S ., Tucci, C ., Zaman, M .B ., Melamed, M .R ., Kiely, M ., and<br />
McKneally, M .F ., "Lung Cancer and Exposure to <strong>Tobacco</strong> Smoke in the<br />
Household," The New England Journal of Medicine 323 : 632-636,<br />
1990 .<br />
Conclusions based on a case-control study of 191 men and<br />
women in New York State were reported in 1990 by Janerich and<br />
colleagues, who wrote :<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Exposure in the workplace was measured by<br />
recording the number of smokers who worked<br />
with each study subject during his or her<br />
lifetime and the amount of time the subjects<br />
spent working with these smokers . These<br />
<strong>exposure</strong>s were compared for case patients and<br />
control subjects . Estimating the odds ratio<br />
as a continuous variable for an equivalent<br />
differential of 150 person-years of <strong>exposure</strong><br />
gave an odds ratio of 0 .91 (95 percent<br />
confidence interval, 0 .80 to 1 .04), indicating<br />
no evidence of adverse effect of environmental<br />
tobacco smoke in the workplace . [emphasis<br />
added]
t<br />
f<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
.J : 'k---THE \Etl E\GLk.\y fOIQ•v,U, of mCDICt\E<br />
LUNG CANCER AND EX.tOSUitE TO 7•OSACCO SMOiCE iN THE HOL'SEHOLD<br />
D~,toxT T J, .t>P<br />
prnalttnq an0 tuhq canC .r es ot qrtat pupt,C Matth rmM•<br />
tdnoa rS4mi pffvtous ttutl,ts hava Wq ;tttro that txpP .<br />
aur• to MvtrOnmfnta1 tLCaCco lmptti m!rN AouNnOtO<br />
can uus4 tunq cancst• W ottWn Mva tarnd no anatt .<br />
Snw+, .inQ by mi spousa has bftn Pha m0i1 COAtMOnty<br />
us .c measurt of t'h,s atposur•<br />
blrrfzoas In ord .r to W ttrm,na wharhar k,nq ca•+cyr y<br />
anicciata•6 w,tr axposura to tobacca smo+c• wrCvn ma<br />
MuselroiC wt conaucu-C a paputaton•basea use•••con .<br />
trot Sludy of 1qt pat,tnti witn hiitOtOQ Ca y Wn1i Ky pn•<br />
ma'y tunQ canct, w*a haC rNvt• amoksC dn0 an ~ua<br />
numthlr Ot ptrsOni wtth0ut fung CanCar wtto ha .'. M1fvpt<br />
trnokoCS Ltatima rts,0tnlia ; hiftonaS tnGIutltrg M1tOtTn&•<br />
tWn on ttp63utt to tnvironmtntal tobacco 1mOtcf wart<br />
OOrnp1llC and ana yYtC ExpOtWp waa fiRasurlO,n Itrma<br />
ot'sToka'•yaa't catt'r+,ina•C by muqtp+y,nq tht numbar<br />
of ysars fn aach rall0anca by 1fH numbar Ot trnpk!•'Y dn<br />
" hous .haa<br />
T HE 1972 Surseon General's report dealt with the<br />
health consequrnces of passtte smoktns or en~i•<br />
ronmental tobacco smolte for the fint ttme ` In 1986<br />
the entire report was de%oted to the usuc : it concluded<br />
that ••rn\olunlar\ smoktnS is a cause of disease tnciud•<br />
ing lun>S <strong>cancer</strong> tn healthti non•smolers "= llore than<br />
a dozen tptdemtoloStc stud,es ha .e a3srssed the rela•<br />
tion bet"ten patsa~t smoicani and lun ; <strong>cancer</strong> }'r The<br />
(indine ha~e ran5ed from no detectable increase in<br />
nsk'"' to a moderate (about twofofd), stattstiealir tis•<br />
nificant incrcue "Most studies ha~c found onlv<br />
small ele~ations in risk, which art frequently not >.hu atrs ctrmCil*we 13 ea<br />
trrt .rsth approxtrnact}, 125 4uSnwuc tar ttrsnR+ent fac,t,lm an<br />
ppu4uan Yaar sf ntarf~ 10 mtllwn pevplr , tprttai rtlrm fa<br />
rap .d autrtunmrnt k tasrt o( tunt cbnctr rac n+ablahM! ln th<br />
115 tactluln to lha, panrnu cavl@ ar .denliRrd and ennikd u a,<br />
afirt d,aq++osrt u pats,btt ilt we- taat+ ef 1mnK canrn ,i .atrno<br />
etMfcail,, k;utolorcaJt., of bothl trt rtrulaN, drn,rfifd a,<br />
pnx,t.ann; hoep,uL 't'ht %*t• . 9'ark State Can :r Yi.t;uln<br />
thtekrd rtwtanti• ta .drnuh an- r~ ,Aa, .eyh, aa~t bt•rt a4i<br />
1e+ I~t~+t~ ~lwt~p,ui•Kaard lte~Ywrtl>K t .arm<br />
l~1lV,il4ttan tn tin~i,t4 MaJ7 lNL{ltltv ab1a111rfJ frs~ n1t'!tY<br />
mrdfesi rre .rdt A1i tht tatr Ptcxau npntd u MaweS w,<br />
tn,owrd .r u k.mrr smckan of .k,aw fn+atMt t+urr, eu<br />
tAc.w KK ttmtattk ia . utr.phau and thrrr smsiny tutw<br />
tanarYned Te Ya Mdudcd u a'tare' M tlu atwt ., a pnrnt R.<br />
rts,It IA 11N TJi'BUnf,, ans k 4tt•rrn 2@ an6 /0 .esn rf<br />
Wvtr lu .t tmoktd R+ort t}un tt70 tysrtltn lnansnwlrht of t<br />
1TOl,rif at tWnt UR1t aul nat lU~t tlf+6ard t>sart than 100 c1rtP<br />
i . tl.t It) +tsn Yn•fort /urart t6a .+nrr an+skrni W ka .t i<br />
~ n+ . tiufi,au .t pnrnan iuty tYetn Irtwern Juh 1 1!i?<br />
Ckcrrnber 111, 11i+ . ttul .at etMfirmt! sr, rresaft .•tt .an et<br />
'athoi,ficiJ stecuntns anal chnltal rtcarda Stfde+ w NaW o,<br />
wt .rrr a+i"tat>'k Sof all kat S,'t at tAt tast'atKnn U7 rnatt<br />
an rtnt•. .ed 4. MrtsnSston he .as fttndrd vrcF rrapa•ct I<br />
~suert's rueul dla~no+u anokuq l»loe~ aM atMrr rttl iaf<br />
laumw .+ t .erc c+Rductad .ttA 16 ;wrrcent ®( +ht rt.g~btt p.t~<br />
at tAcu ttoet+t avutaak retauvek s+ hunAt twrrqtt"t<br />
Conti'9t aYIt)tSu trt tadlvdual1r r+auhed t0 ls4 tsurriu<br />
tie+v stirctrd !r scrstnlry ttx >Tiln t( thr wr. Yrri Stttt dk<br />
sitxt .f t,{ata Vrlucln T'4r trrrrt .f can+rolr .u t4rs),<br />
apptt+¢tult kact It ru p»putaust.ba .ed anA prro .Nhd aws+t, c<br />
rsarnuuon atcruar. to perforra t!t anatch,nS A bi af po,<br />
tor,trct tut.pecu fw tatR uat paurnl .at wLrctrd .n t!w iss<br />
a ;r (adun f vt vt+nt, trs . and twMr. .! m,drncr Pstrnlu<br />
trot eub)rtu wtts trntantd b+ ukpl,ofu TTt finl el+t+tatt n<br />
rho as Sound to nutth tAt sast Hl+znl tn trrmi st nnoa nt<br />
ty tttionstnsirr st Sormcr tn+alrr t and aw aS+red ts Wlnps<br />
enrollyd u tht stud~ An add,lwnal ~sctch,n~ ~ansbk carudr<br />
thr umt .( dlta COLKUas aao tht nqr .I u+ttnw . - t t ._<br />
ifttcrv,c~ rMti, st,t pawnt .f caAwt tuh)ect .tnut r+lmuv<br />
wrrnisu respaMent WAtn a surr .,Ktu caa< ptiunl 1,ad<br />
i.urrvx ...r/, .t a.too u+unuor! s wrtnSsu tar As w k.t1 m~<br />
~iqV<br />
~rl<br />
J"A<br />
~<br />
~<br />
I
t<br />
%ol ;:1 •o lo LL''%G Ca .NCEi< kVD HOLSEHOLD TO1+CC0 SMOKE - JkNE0.ICH ET kL i1J<br />
I control r%~n .ehen the control tublect .aa avatl.bk arrd rnUtry to<br />
be tnttn/t-td Furthrt tn(ormatwn M the entt6ait tued tn tit<br />
uud, u atat4bit rlae .hert 't<br />
Data -ere collrctrd (or 459 c .ae-tonlrol P.atn CN thste . 242 lun<br />
utre lonntr tmokrn and 191 paun had ne-tt swwhed Btparaunt<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
the rettdual ttfecu of d-rtct a+noktnt froen thae t! µur .t em.ttnt<br />
smone iormer amokrrn bn .oi+ey more compln anal.ttc and wtter,<br />
prrtstronal uturt thsn does an rsamtnaasler n( ust t{fecu a'! `aaa,r .t<br />
tmok-ne m thox -ho hatt ne+er tmoked This report a tl+nr{nrt<br />
itmtttd to perwnt -ho ntt tr tmoked Su al the 19 % ptn .ho had<br />
nr'er tmoked -tre mumatchtd tn trlm .t sf tht w*t .( ntervr+<br />
~dtr/rt ts wnotate and ha .t thr•rriorr Oetn ntluded Tltya, the<br />
anal .ut rrpotted htn -ere 4std twt I91 taatche•d caae-contrel<br />
pain k Ltal a 1 :9 pain .trt rwtmsir.red titretltt . twd auetnatte<br />
atrl /AIttYK.td ttJr B :<br />
411 mlorminon .at collecuel dunnt a tan•ewfacr xttrn .e- w+th<br />
ute oi a®rtcoded que+twnnarrt Cau'autnu and tanlrtl iuyKU<br />
•ert rntente-ed tn t%actl• the tant . luluon and nct)tt iol uetw<br />
concern,nS the clinical aapecu ta( thr currtnt eiAedrtaw condtuon,<br />
both troupt ant-rred the tame qur+t .ont<br />
InformaHon about tmoktnS m the houuho7d .u eollened .rpa•<br />
ratrl, ior tach re•midence rn rhieh the tubjrci had Irvrd for one .•etr<br />
er more up to a maatmum of 12 reytdencta Tla number s( 't+noktt•,ran' of tcpo/ure -at calculated Is, tnuluplant the numbrcr of<br />
aart the aub)tct li .ed in tach rn dtnce bs the numrrr s{ smokm<br />
lrnciudint tht epousei tn tha{ rntdenct TAt }loducu fol aA retr•<br />
dentef ~trr tummed<br />
SmWtnt b, the spouse .ta a1w reeoltftd .epanrel* frvm that In<br />
otfier houtchold membert rn a aub .equrnt aectton t>t the quntwn•<br />
nsut The tnformation conture•d o! the number o( tan the tpeuse<br />
had smoked .htle httnR with the t"e paneni or eontrol tubltet and<br />
the number o( ntarettes tmoktd oer dat Smoktr•vtan of tapeurt<br />
6om the spouse a tmokrnt wttt eakulated m the aame manner u<br />
fm the entire houuhold Psck••ean sf eapaure (rom the tpou .e<br />
.ere calculaied b+ mulupl .tnt the eumbr. al packs emoked ~er dar<br />
b• the number or .ran that thc apouse emoied .rh,le Irv .nt .rth the<br />
tublrci If the fublect had besn mamrd to mon than one tmoirr,<br />
thtn Ihc numben o( tmoker• .tan and pack• .ean a( ea"ure kr<br />
all spouses wtrt tummtd<br />
The qutattonnatrt also tneluJed utt .au t+n npewurt tn t•nnron•<br />
menul lobacro amoke tn she workplaee and uM ooauJ setunp wl•<br />
a+dr Ihe home The Ioraut (or the+e aluetlweu tlldered Gom that<br />
axd to cs(ltcr data on espro.un ut the househoJd 'ftie sumeaan<br />
results of thu anal,tu are Preunrad Aert, dewled [ .dusr an<br />
stulable elsewhert 't<br />
Staiutteal tKhntqun appaoptutt be the anaJyua d tt.d nduallr<br />
matchtd cue-control ttTn .tn ated se For tlutn t .( plesewu•<br />
tuon, percenutn wtn ubuLted !or ux pauenu and tsntrol eub•<br />
)tcts trpsntel+ rather then for ttute6 .d pun Hc erer• tddt rs•<br />
uot wert eomputed ae+ the l .aut .f tl+e .+.tthed pun The<br />
conditionaJ IoTauc•ttfreaaron .wdd .u u.ed ta tht ntJuvwte<br />
aNlvsts " ComparuoN o( tJtt el .<strong>ets</strong> ttf uroaurs that Kcurr.d<br />
dur .nt dt(frrtnt penodi of tlt aul?eeu' 6'rvu rtn "u'd .n t+ralut•<br />
tan e( diRertncs ia the tnt{rutudt sC appropnau fatuuc•rttrrt•<br />
aron eoeRtnenu Feu tuusueaJ traaj .l tkest Iiffcrc.cet we<br />
used the v.runer-evvatianu nuuu Loe>, ele bRstuc•rsrtursn<br />
ar+ah.ea<br />
Xxx"T$<br />
Smoking by spouses eontributed a Large propor•<br />
tion of lifetime e:posure to environmenul tobacco<br />
smoke but was not the chief source of expoaure . Tablc<br />
I showt the amount of expoture to env'uonmeniml<br />
tobacco smoke (expressed in amoker•yean) dunng<br />
childhood and adolescence, during adulthood, and<br />
from the spouse for the 191 control subjecu who had<br />
never smoled, There were only amall dilTcrencey be•<br />
twctn men and women . The spoux contributed about<br />
30 percent of the lifeJme amoler•yean of <strong>exposure</strong> ;<br />
the correlation eoefficienu for expo .ure from the<br />
spouse and lifetime <strong>exposure</strong> were 0 .37 for men and<br />
T .ot. t Oub9otmx+ d+ fv+Or•Y .en a E,tttcwurs 90 Enwrmn .,<br />
tNyrLl Tpp6eioo w+ tN Mpstai+'0'Z a<br />
C,naat w tyt+u+t<br />
Lqam teenar•}rr*,<br />
eatan tSD<br />
Y asll 7<br />
$2 1242 1<br />
sa+u' - r'++r+ 6'nAi ca,'Mil°w atl aittaowts'<br />
+Mweso tsa[X7a K 1916 2<br />
Mtrr M bltMa ttAaet 7) 1 )0 4<br />
Ct/nuw . vt>'o dtttewt tait.n S 91 9 tt<br />
sr .<br />
a,. .•<br />
fw+an'raww ktw etewre<br />
t+ltao aiD 1)es110 N1s/1t<br />
M/crw er 4{"nu tarywwt 2J 0 IO '<br />
Cesnuot• ase t.tni.r tyaesit 9)1 a rt<br />
rwAilr'rt4S t•f1a4 aeUMr !M M~ MPt tkM tp~<br />
aau., sSD It Isll 0 M 1t :11<br />
ratr. tt W .a est. .re x 1 s4 t<br />
Cavnls.r l.0 kH.1to tyeart a N 01)<br />
•a .r . e t - t9 r• . .sat a .* nw tL<br />
.qr.r W ..,r. r etta.w r+ ft r. .• . b e7 a . . aa rd<br />
t..w er . r .r. iwa~ s, .n ~v~. t. .,rss•+t w .rr. r wtw ue<br />
•t.aww.l, ~.arMai<br />
0 .$1 for women Exposure dunns childhood and aclolescence<br />
(
f<br />
634<br />
Taar 2 n«aW ot 5"Okr rw's oi EAao* .rn o E'M*orr,.r,w<br />
tooaaz SM+o.e to e++ t4ak o+ t-ur+q Cancw ar+onq r .'sa,a wr,o<br />
rr.,- .f SMMr•a tao•e rrW t0o Cpannn •<br />
~<br />
t . .raaa tfi,a LM .n C.-r+... hrt.qrMadl<br />
cti~ rw .. ..~«,k .<br />
0 71 .1411 61J7 6i<br />
t- :e {~ lJ 1 M 0t I)<br />
.rd fi ~i~ a T it! Ii<br />
t . V rT Itt U<br />
3.iloer<br />
AI 115 t+<br />
M ile ti 10 34 3<br />
!0- e<br />
.'e<br />
L1ronr<br />
3r,1tii<br />
:t li .ri<br />
SI0le,<br />
. s i ns 1<br />
0 3I ~tf /~ 33 ct' 3~<br />
- :+ :o~to31 I~'e u<br />
]3-J. SS~u3 ..,ten<br />
x1 . u I u 01 ao '20 .,<br />
33 tt+ 31 It iu 01<br />
• IM :j 114 u : . 11, 6,<br />
S}{B VEw [VGLA .vp)Ol-'R.VAL Oi HE.DtCNL irpi t ifX<br />
t e*,O 66-1T31<br />
3010 tf.-3Mi<br />
0 rr i0 1.-t tt~<br />
anro<br />
1 110co 17-1 e3t<br />
t ti i6 3t-I `•6I<br />
•s ..» . t~ ~ - ,.n a,.. .. iw...~ chf.,.. «<br />
w. . io . r.w .w r ... . ..• -..r . .... .r. .*e As<br />
•e ~..~. ..~ a..- « ft•..µ .... ... d. .. a . .n .. Ne<br />
sr I i fon .i AP<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
durins adulthood were eitimated to have nnualJv no<br />
efTect on nik (95 percent eonfidence interval . -3 .3 to<br />
2 B percent) The difierence in xhe maMrude of the<br />
eR'cct bteween <strong>exposure</strong> dunns childhood and adotescence<br />
and <strong>exposure</strong> dunnS adulthood did not achirve<br />
Ltatutical st5ruficance (P w 0 12) . On the buu af<br />
the distributton of <strong>exposure</strong> le-,eb dunn` cluldhood<br />
and adolescence among the control subjecu and the<br />
masrtitude of the effect of eauly expoture, we otimste<br />
t~t approximauly 17 percent or all <strong>lung</strong> earurrs<br />
t norumokcn can be attributed to totpcsure to paasive<br />
smoke i.n the household duriq ehi.idhood aM<br />
adole+cence . On the baau of the oddi ratia{ for<br />
the 129 case-•control pain wbo were iatervicwed directly,<br />
approximately 19 percent of <strong>lung</strong> eaneer<br />
in norumoken appean to be atuibuuble to expaurt<br />
to environmeatal ci{uene amoke in childhood aad<br />
adolncencx .<br />
Since srnokin= by the rpouae hu bren the tsWrt<br />
commonly reponed mcaattn oC cxpo{urt to environ•<br />
menta! tobacco atuoke ic prtvious studies, we eresmined<br />
expauze hom tbe spouse txpantely, att}sougb<br />
<strong>exposure</strong> to et+virontsuntal tobaecv acsoke from the<br />
rpouse is also included in the tesuJu shown in Table 2 .<br />
The odde ratioe for <strong>exposure</strong> frequeatly d;iffercd ac•<br />
cording to the rype o( intervieti ., etpeelally for the<br />
dats on <strong>exposure</strong> to a apouae's smoking Table 3 xbtrrfore<br />
shows the reytilu of the ansJysn of <strong>exposure</strong><br />
to environmentaJ tobaceo smoke from t3te t;pouse<br />
aeparatciy for subjecu irtterviewrd directly aad tborc<br />
for whom sutrotata were irttt:rvie.wtd . T'be odds ratio<br />
for the dcvelopment of Ittn{ <strong>cancer</strong> for t6cxe who<br />
ever had a{pouu who smoked, as eomparrd with<br />
those who did eot, was 0 .93 (95 percent mnl,dcnee<br />
interval, 0 .55 to 1 .57) for tAo.e interviewed din•ctly . t•<br />
tct•r:u of amoker•yan or tapoattre to the {pouse'a<br />
smoke . the raulu abow little ef!'ert, with an odds ratuo<br />
of 1 07 for 25 or more amoker-vean of <strong>exposure</strong> t95 `<br />
percent confidtnce intenal . 0 .59 to 1 .97) . Lumatet ~<br />
based oe pack-yean of cxpoaure from the spouse were<br />
{,rrtitar to those bued on amoker•yean For botA<br />
meuuret, there was little evidence of a trend accord•<br />
usf ta amount of <strong>exposure</strong> among those who were<br />
expoeed .<br />
All analvsn were repeated for onlv the ust•-control<br />
pa3» for whom we had complete and internsllv coniutent<br />
data for all mtdenca and mams`ei Anv patr<br />
wai dropped from these analyses if data wtre tncom•<br />
plete or musinj for either the t:ut patient or the control<br />
subject, kavtns 113 paiR of nonsmoker•t Our<br />
purpose wu to eniure that our eonclus3ons were not<br />
dependent on the particular methods we adopted to<br />
handle utcoWi{tenctet or misstn ; uerru in the dau set<br />
The findingi were stmJar to those for the entire group<br />
of 191 pun Tht odds r:do for <strong>exposure</strong> to 25 or more<br />
tmoker•yean in childhood and adolescence .+u 2 .59<br />
(95 prcruet eonfidence utttrvsl . 1 .22 to 149)<br />
Laposure in the workplace was measured bv recordin`<br />
the number of smoEen who worked with each<br />
study subject dunng hy or her lifeume and the<br />
amount of time the subjecu spent working with<br />
thex {mak<strong>ets</strong> . These eaposurn wrre compared for<br />
uae patirnu and t*ntsol subjecu E.rumannt the<br />
odds ntio aa a continuow vanabte for an eqwvale»t<br />
differenaal of 150 perwn-ytan of <strong>exposure</strong> save<br />
an odds ratio of 0 .91 (95 percent eonfidence tntnval,<br />
0 80 to 1 .09), indicatin` no evidence of an advene<br />
effect of envtronmenul tobacco amoke in the work•<br />
place, Our aaaeument of smoking in soctal setaap<br />
used an un(ntrd, aemiquanatauve u+dea ut wlueb<br />
the cau patient or control subject used a{eore of<br />
0 throu`h 12 to indiute hu or her retui .u expc .ure<br />
to tobacco smoke in social settinp dunn` each decade<br />
or tife . Cumulative iifeume rtponed awra tunFed<br />
from nearly 0 to rrwrt than 70 . The odds noo for an<br />
increuc of 20 in the t:umulative aeart wai 0 .59<br />
(95 percent a,nlidence interval, 0 .F3 to 0 .11) . Our<br />
analysis of atpo.un in tadal setrin,p vnt,d nse of<br />
ti,is inda sbowetd a{uriatiealJy {isntficant invrne utweiatioa<br />
ber .m tavironmenut tobacco atrt,oke usd<br />
Iu3y Causer,<br />
I)sacu1.91094<br />
We iound a suuitiutly sienificant adwert+e es'ea<br />
.m reLdvely high kvelzt o( esporurt to enruvnrtmataJ trobaceo<br />
saiole dutin ; the eariY decadn of life (up t9q t,lwe<br />
aV of 21) . For ebo.c wbo wcre e:poed ta 25 oe tseat<br />
amokcr-yeua du.riag tbeir 6rst t.w dendea of tik, tbe<br />
rial of tuni nacer doubled, Tdia tim*unt of aporure<br />
i{ equiwltrit to tiviag witb, tt0ort thaa ow tuno&erN<br />
tb.roullbout chiidbood and adai*=ct - a lil* bsttC<br />
troc uaooauaoe icvd of erpwurc. Aa expxur~<br />
this level was rcporud foc apprc:zieuately IS psreeat<br />
the enettrol group 15y eootraat, we found no a,~<br />
e!!ta or ctpaure to eaviroamemtal tobarxe t+<br />
dutin{ aduJtbood, indudin{ e:pown m a aporr. +viC,P1<br />
).A<br />
NOLA<br />
CID<br />
N
~ ol )2! \o 10 LL'NG C .~'sCER t`D HOLSLHOLD TOMCCO S .~tOKL --J{ .\LRICH ET kL .1J :<br />
T`Dis 3 t+4auor+ e Soousa s S+rok,N to trv oknt or Lwq Cancs,<br />
amo/r, h'soSo t lo to .7•Z 141<br />
f .wr/. .n• . .<br />
0" .. . Af. U h<br />
•uiOH-i02i<br />
aurolt•los1<br />
1uto l : .oa<br />
outoo. . .o$V<br />
ou'ou-tso~<br />
ea)4 oo) .i 1]i<br />
• s ur . : r , r-. . ... . .., .~.~ ... ...,,, r f. .w 1. ., .. .++~ . .~.<br />
..- . . .r rbw ., .._/~rv. ..w, .,r.r, .. .,.,. ..+rr ..r .... ..<br />
.,n-t .Irw, .r i- .4er N W K W,~ e .W w .ab pu r ... .~<br />
f. iT urr ..u.~ /.r .4 Ivr ~ .. .r M/r+~<br />
o. . .~ sl w.+ r .,r.+ - n .u .. 1. i :J .,n .,w<br />
Ci a- RL._ ..« . Or.<br />
rywi. . 1 r. . w rrr<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
smoked, Although problems of recall and other poten•<br />
tial biues may have influenced the raults, our data<br />
suggest that <strong>exposure</strong> in earlv life may be a limited but<br />
important contributor to the nsk of <strong>lung</strong> <strong>cancer</strong> in<br />
nonsmoken A previous studN wit}t a smal' number of<br />
subjects found little evidence of an elevated nsk<br />
of <strong>lung</strong> c.ancer among nonsmokers whose parenu had<br />
smoked " Children of parenu who smoke ha%e been<br />
shoMn to be apeciall% suscepuble to respiratory prob•<br />
lems that occur soon after <strong>exposure</strong> to environmentaJ<br />
tobacco smoke,s This type of suscepubifiry might<br />
initiate changes that eventually lead to <strong>lung</strong> <strong>cancer</strong><br />
when the exposed children become adulu, but we<br />
know of no specific mechanism that would explain our<br />
findings<br />
We found no adverse e(iecu of <strong>exposure</strong> to tobacco<br />
smoke in the workplace, althou`h we did not have<br />
enough information about the bevel of expo.ure in<br />
the workplace to auese the precision of our meaiure•<br />
menu . The apparent protective s:fiect of <strong>exposure</strong><br />
in sociai aetunp is difficult to explain . During the<br />
course of this study, s,etulations in New York began<br />
to restrict smoking in the workplace and in social set•<br />
tin`s such as rcstauranu . We did not anticipau thiu<br />
development and cannot estimate how much the<br />
awareness of these new ratrictions might have af•<br />
fected the responses of the study subjects or their<br />
surrogates .<br />
Evidence is clearly mounting that tobacco smok .t<br />
inhaled pusively by tsonsmoken is potentially cur•<br />
cinogenic . In a recent study, Madure et al r' found<br />
elcvated levels of cardnojens in the blood of pusive<br />
smokers Levels of hemoglobin adducu of 4-aminobi•<br />
phenyl and adducu of 3-aminobiphenyl were sig-nifi•<br />
cantly elevated in subjecu with confirmed exposurc .<br />
The validiry of this findinj was supponed by addi•<br />
uonal evidence that showed a tharp declir.t in thr<br />
kvels of adducu among smokers who quit'<br />
At prnent, information on put <strong>exposure</strong> to ent,<br />
ronmental tobacco smoke can be obtatned onh b•<br />
interview . The available biologic marken, such as co<br />
tinine, cannot be used so confirm <strong>exposure</strong> that ox<br />
curred years or decades earlier . The use o( tntetvse• :<br />
to obtain a lifeume history of <strong>exposure</strong> to puu
1<br />
J<br />
836 THE 4EW ENGL,IND JOU0 .NA1 Or 1lLDICINE Lrpi G . 111110<br />
of <strong>exposure</strong> also failed to exclude the null valut"<br />
Garfinkcl et al„' using a difierent mcuure for durauon<br />
of <strong>exposure</strong> (husband's smoking in the lut S and<br />
25 years), found one si`nifiunt usoctstion among<br />
the large number examined Exposure due to smoking<br />
b% the spouse . cxpressed in tcrms of pack•yeat :<br />
while the spouse Aas li%~ing with the subject, wu<br />
Wund not to be sifnificantly associared with lunj can•<br />
ttr . Using a comparable measure of <strong>exposure</strong>, Trichopoulot<br />
et aJ 1 reported relattvelr large increuei in<br />
riuk (treater than twofold) 1'erhaps our data do ssot<br />
ahow that smoking b~ the spouse increased the tisk b .r<br />
itsclf beuuse smoking by the spouse made up only<br />
about one third of the subjecu' Iifetimc <strong>exposure</strong><br />
to cnvironmentaJ tobacco smoke It is aiso possibie<br />
that phvncal circumstances and dtfTerences in studv<br />
areu . the size of retJdences, vcntilation . and other<br />
importan ; phveical aipecu of the ltvtng condition>,, u<br />
well as social habits that alTect <strong>exposure</strong> within the<br />
familv, will need to be measured and Inahied before<br />
tbe diAerences in findings among the studies can be<br />
eeconciJed<br />
The evidence we ttpon lends further support to the<br />
obsenation that passive smokunj ma% snerease the<br />
risk of subsequent <strong>lung</strong> t :ancer, and it sut`esu that it<br />
vta• be parTtcularh important to protect ehildren and<br />
adolncents Gom thu environmentaJ hazard .<br />
'Ae art tndebted to Mdrtas Vuei .ou tot hu usuunte -th the<br />
t:ompuur 2rraSTarnnunt uaed tn .ur anaJ»n<br />
RtlL1t.NCtf<br />
J t7lAL~ .r /{r1t tlsaman rt! M t iroe T1o e ..M e.. ..K,.nr~ .f<br />
.rst t w . .n w+ w i .p ... Car,, tY J r rhNr« D c Cs. ,<br />
?f•ro+r. ttiw" ONa . N'212 ,)1 tD+Q'w rs"arw ttuMt)2<br />
: Defv*nnv sr ka.R rt Nu,va S.-wa Tle t. .la M ..eo.+•.. M<br />
a•»i~ ura.nt e+hv+ a wr LrT .aa tie.arL' *as+weasr D C<br />
G*•.n.r. .. r4uey pss . tKt (t'mssm as oHMS tC'OC1 17 .<br />
1NC1<br />
2 Cwfiue) l Tt.r rraei r Jteed ooienr nerralrri .re^t .oe.notn .r e<br />
s N M.u .e rs>tiy 1 P4tJ t:ar.. W 1991 . Y t0i t•<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Ma .fsaehusctu MedtcsJ Soorty<br />
Irgistrv on Conunuinl Medical Edueatioa<br />
4 Nrri .we T Cr ~ruM % t-mkaet •wa .wy, w<br />
.rrp Whwr, a<br />
.rt r a MT wJe arr^ r7 a MM Ow . Nu 1%- 1) M6<br />
S Yncrw I ..tw 0[eiau/.h A, . aatrne L t.q sv am pr+a wv .t<br />
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h,.t knt aa . ^ew at ..wrrr a wq Kaq 1 ay h Cr.<br />
aa IW .Il..)i7 .7i<br />
To obtain iLtformation on continuing medical education avurxs ia tht Wev Entland arem,<br />
ea11 berween 9 :00 am and 12 :00 ooon, Monda7 through Friday, (6171 /93•4610 or sa<br />
Muuchuscru a•i00422•2303 . tKt 1N2 . lf writin{, direct eertespondenee so f4o"m<br />
ltejurar, Musschusetu Medical Soeiety, 1110 Main St ., K'alsham, MA 02154-IH9 . The<br />
booklct r free to MMS memben . IS 00 for aonmembert
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
5
Kabat, G .C ., and Wynder, E .L ., "Lung Cancer in Nonsmokers," Cancer<br />
53(5) : 1214-1221, 1984 .<br />
In 1984, Kabat and Wynder published results of a case-<br />
control study of hospitalized individuals, mostly from New York<br />
City . A total of 25 male cases and 53 female cases and their -<br />
matched controls were included . The authors wrote :<br />
The plausibility of a role of passive<br />
inhalation in <strong>lung</strong> <strong>cancer</strong> can be questioned on<br />
several grounds . . .<br />
Cases do not differ from controls except for<br />
the greater <strong>exposure</strong> to cigarette smoke at<br />
work reported by male cases compared to male<br />
controls .<br />
The authors reported that 18 of 25 male cases versus 11<br />
of 25 controls reported being exposed to ETS in the workplace .<br />
This result was statistically significant at P = 0 .05 . The point<br />
estimate for workplace <strong>exposure</strong> of males was reported elsewhere as<br />
3 .27 (95o CI 1 .01-10 .6) . However, the authors' reported results<br />
for women are inconsistent with their conclusions on men ; 26 of 53<br />
female cases versus 31 of 53 controls (i .e ., fewer cases than<br />
controls) reported <strong>exposure</strong> in the workplace . This result, a point<br />
estimate of 0 .68 (95% CI 0 .32-1 .47), is not statistically<br />
significant .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
Lung Cancer in Nonsmokers<br />
OECtFFREY C . KABAT, PwD, AND ERNST L WYNDER, MD<br />
NOTICE<br />
This material may be<br />
ptote :ied by<br />
isw (TiUe 17 U .S . Gode) .<br />
Among 2663 prtieats with aewly diagnosed <strong>lung</strong> <strong>cancer</strong> laterriewcd between 1971 aa.d 19a0, 134 cases<br />
«ecvrred in ".alid.ated" .oascsokerx . The proportioa of .oascwkers among all tases was 1 .99k (37 of<br />
1919) for tsuo and 13,0% (97 of 749) for women, ririag a sex ratio of 1 :2-6 . KreybetY Type 11 (mainly<br />
asdetwcarrirsoeu) was more common among nonsmoking cases, espaialty women, tttan asnoa= all <strong>lung</strong><br />
rocer tssu . Comparisoa of tases with equal numbers olaqe-, sex-, tace-, and Isospitil-tstatcised oaumoking<br />
eonerols showed no diRerersces by nligion, Fropottioo of forcigrt-born, saariai sntus, raideoce (nrban/<br />
mrai), ako6ol coostrmption or Quttelet's Isdex . Mate eases teaded to hare Yi=her Froponioos of profes•<br />
sionals and to be wore eduated than controls . No differences ln occvpatioa or tsocnpatioaat <strong>exposure</strong><br />
were seen in roen . Among women, cases were more likely than corttrots to La•t worked in a textiltrxlLted<br />
job (retati .e risk - 3 .10 . 93% confidence iater .al 1 .11-8b4}, but the signifiusKe of this finding<br />
8t not clear . Preiimitnry data oa <strong>exposure</strong> to ptissive itth+lation of tobacco smokt, a*ailable for a subset<br />
of tYses and controls, showed no diA'erences except for more frequent <strong>exposure</strong> among male cases than<br />
eontrots to sidestream tobacco smoke at work . The seed for more complete informatioa on <strong>exposure</strong> to<br />
s+ecoadhand tobacco smoke is discussed .<br />
Gtwter 53 :1214-1221, 1984 .<br />
NfA,e.cr,' l<br />
A LTHOUGH LUNG CANCER risk is strongly associated<br />
with cigarette smoking, <strong>lung</strong> <strong>cancer</strong> dtxs infrequently<br />
occur in nonsmokers .'-2 Several features distinauish<br />
<strong>lung</strong> <strong>cancer</strong> in nonsmokers from that occurring in<br />
smokers. First, most eases of <strong>lung</strong> <strong>cancer</strong> in nonsmokers<br />
are found in women .2-y Second, the d'tstribution of histalogic<br />
types of <strong>lung</strong> <strong>cancer</strong> differs between smokers and<br />
nonsmokers . In smokers the epidermoid type predomi-<br />
From the Divrsion of Epidemiology, Mahoney Institute for Health<br />
Muntnuna, Amenun Health Foundation, 320 Eau 43rd Stseet, New<br />
Yort, New York .<br />
Supponcd by National Cancer Institute contract N01-CP-056t4 and<br />
grant CA-32617 .<br />
Addras for reprints: Geoffrey C. KabaL rtsD . Divis+on of Epdemiolo{y<br />
. Mahoney Institute for Health Marntenancs. Amenan Health<br />
Foundauon, 320 East 43rd Stroet . New York, NY 10017,<br />
The authors thank the fdlowtnj txoqerauni ; institutions and individuals<br />
(or their a)uabk contnbuuons : Memonal Hoapital . Dr . Devid<br />
Schotankld; Manhatun Vetensn's Hotpttal . Dr . Norton Spritz; Long<br />
ktand-Jewish Hillside Medical Center, Dr . Arthur Sawitsky; Uaiversity<br />
of Alabama Hawttal, Dr . William bndrm; birmirraham V<strong>ets</strong>ran's Hospital,<br />
Ds . Herman F. Le?tman : Layota Uoisrsity Hoexul (Chica=o) .<br />
Dr . Walter S. Wood: Hina Veteran's Hospital (Chia=o), Dr. John<br />
fhup ; Hoeplta) of the U .iversity of Tennsylvania, Dr . RoEen M . txrin ;<br />
Jefferson Medical Collese and Thomas lofferson Univatity Hospital .<br />
C?r .1 . E. CotbtM Allegheny t'xneral HoepiW (FitttburYh), Dr. Sunley<br />
A. Eriller, Universiry otHttstwrfh Eye atxi Ear HoepW, Dr . Lewis H .<br />
Kulkr, rittsburflt Veurran's Hoapital . Dr . Eusenc N . Mym; MoRrtt<br />
Hospital (San Francisco). Univtrsity of Ca)iforni+ u San Francisco and<br />
County Hospital (San Francisco), Dr . Niehotts htnicir and St. Luke's<br />
Hospital (San Francisco). Dr . Richard A . t3ohannan . The authors also<br />
thank Ms. Marpret Mushinski for her collaboration in the exrly staaes<br />
of this study . Ms. Nancy Vrouoc for programming assiuanct, and Mr .<br />
Monte He+son and Ms . Mana Nanfiro for manuscript preparation .<br />
Acrcpted for publipuon August 31, 1983 .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
1214<br />
nates, whereas in nonsmokers adenocarcinoma is more<br />
common, especially in women .2-s<br />
This article presents data from a case-control study of<br />
nonsmoking patients with histologically confirmed diagnoses<br />
of primary <strong>lung</strong> <strong>cancer</strong> with rtspect to histology,<br />
dernoQraphic factors, residence, Quetelet's index, alcohol<br />
consumption, previous diseases, occupation and txcupational<br />
<strong>exposure</strong>s, and, to a limited extent, <strong>exposure</strong> to<br />
the tobacco smoke of others . Due to the small number<br />
of cases and controls on whom we have infotTrtation on<br />
passive inhalation, the data presente :d here; on that question<br />
are in the nature of prtliminary results . A discussion<br />
of previous studies concerning this issue emphasizes the<br />
netd for obtaining more detailed information on sidesveam<br />
smoke <strong>exposure</strong> and related variables .<br />
Metbods<br />
All txsa of primary <strong>cancer</strong> of the <strong>lung</strong> occurring in<br />
cases who reported never having smoked on a regular<br />
basis' were extracted from an ongoing case-control study<br />
of tobacco-related ancers conducted in a number ofcities<br />
between 1971 and 1980t and described previously .' For<br />
each txse, the hospital ehart was rc-examined in order<br />
to confirm the diagntuis and the absence of smoking ~<br />
~_. ~s*+<br />
• our definition of a nonsmoker was someone who had never smokedN<br />
as much as one tajarttte. pipe, or erfar ptr day for a ytar .<br />
t T1x ma'oAt otthe ases (+nd matctKd controls) were rnte,viewed X<br />
J Y<br />
at Memorial Hospital in New York City, . 30 of the 37 male asea andQ<br />
70 of the 97 femalc easa .
. Vo 5 LIING CANCER IN NONSMOKERS - Kabat and k'yndtr 1215<br />
.<br />
throughout the patient's lifetime . The histologic type of T .a.c ( . Hiuoloy,c Type of t-uns Cancer<br />
.unQ <strong>cancer</strong> was obtatned from the pathology report or<br />
an Nertt Smoken and srnokers<br />
the discharge summary for each case Those cases in whom<br />
Men women<br />
the diagnosts was not pnmary <strong>lung</strong> <strong>cancer</strong> or in whom<br />
there was an indtcation of smoking . even in the remote<br />
(No 1 (41 (No / (4)<br />
past . were excluded from the study . Those remaining in NeVcr emoken<br />
the study are referred to as "validated" nonsmokers .<br />
Kteybera type 1 13 (35 1) 20 (20 .6)<br />
A control was matched to each case on the basis of<br />
age (=5 years), sex, race (with 5 exceptions#), hospitat,<br />
Epidermoid/squamous<br />
(Jttc tt{l/ti .ant cell<br />
Krsyberf type 11<br />
13<br />
0<br />
20<br />
(35 .(1<br />
(Se .1)<br />
16<br />
4<br />
72<br />
(16 .3)<br />
(4 .1)<br />
(74 .2)<br />
date of interview (±2 yean), and nonsmoking status .<br />
Abenoarrinoma 16 (43 .2) 60 161 .9)<br />
Controls were selected from a large pool of hospitalized<br />
Alvealar 4 (10.E) 12 (12 .4)<br />
patients who wera interviewed over the same period as<br />
Miaed (Kreybers I /c 11)<br />
and undiRcrenuated/<br />
the cases and who had diseases which were not tobacco-<br />
anapltutc • (10 i ) S (5 .2)<br />
related . The distribution of diagnoses among the controls<br />
was as follaws: men, 62 .1% other <strong>cancer</strong>s . 24 .3% benign<br />
Tou! 37 97<br />
neoplastic disease, 13 .5% non-neoplastic discase, women, 5mokers'<br />
$9 .9% other qncers, 14 .4% benign neoplastic disease,<br />
25 .8% non-neoplastic disease .<br />
Krrytxrg t,vpe l<br />
KreyberT type 11<br />
Mixed (Kreybers I & 11)<br />
1111<br />
600<br />
(63 1)<br />
(31 .9)<br />
la 1<br />
219<br />
(52 .31<br />
(42 .6)<br />
All subjects were interviewed in the hospital with a<br />
sxandardiied questionnaire including questions on de-<br />
and undifferentuted/<br />
anaplutic 93 (5 .0) 32 ( 4 .9)<br />
moYraphic factors, occupation, occupational <strong>exposure</strong>a,<br />
Total 111 : 652<br />
tobacco smoking, alcohol use . Quetelet's index (ky,/cm'<br />
X 10,000), and historti of tobacco-related diseases . Two<br />
• A mort detatled bceakdown by htstolo ; c typa n not Presentcd for<br />
smokers because this informsuon + .'u not codxd . For the nonsmokers<br />
different versions of the questionnaire were used over the<br />
10-year period, the first from 1971 to 1976 . and the second<br />
thts information vas tetncved tnanually<br />
from 1976 to 1980 . Differences between the two questionna<br />
.irrs included a longer list of occupational <strong>exposure</strong>s<br />
msponses was smaller for the question "Does your spouse<br />
amoke'.'", since this question appearesd in only one version<br />
in the later version, and a longer list of previous diseases and since it was not answered by those subjecu who were<br />
not married, widowed, separated, or divorced (see<br />
Table 3) .<br />
Differences between cases and controls were assessed<br />
by the chi-squarc test for independence .' and by the Mantel-Haenszel<br />
extension test for linear trend .' Point estimates<br />
of the relative risk with test-based 95% confidence<br />
intervais were calculated following Miettinen's method .'<br />
in the earlier questionnaire (diabetes, Sout, bronchitis,<br />
emphysema . hypenension, asthma, pleurisy, pneumonia,<br />
bronchiectasis, and tuberculosis) than in the later version,<br />
which included only four questions on previous diseases<br />
(chronic bronchitis or emphysema, asthma, diabete•s, and<br />
elevated blood pressure) .<br />
Alcohol consumption was assessed in current drinkers<br />
and exdrinkers (combined) relative to never-drinkers and<br />
oxasional drinkers (combined) . Occasional drinkers were<br />
those who consumed Iess than I ounce of whiskey equivalents<br />
of alcohol per day ot beer, wine, and hard liquor<br />
combined . Alcohol intake was categorized into three levels:<br />
(1) never/occasional drinking . (2) 1 to 3 .9 oz/day,<br />
and (3) 4+ oz/day .<br />
In addition, a number of questions on <strong>exposure</strong> to<br />
passive smoking were introduced in an addendum to the<br />
main questionnairc in 1978, and the addendum was rcvised<br />
in 1979 . Thus, information on passive smoking was<br />
obtained on only a subset of the svbjecu, for men, 25 of<br />
37 ases and their matched controi .s ; for women, 53 of<br />
97 cases and their matched controls . This number of<br />
responses was obtained for those questions included in<br />
both versions of the addendum, whereas the numbcr of<br />
$ otu onenuW male case was matched to a white cYmtrol : two hisa.nic<br />
anrM t.vo oaunul femak nses wett matched to whitc controb .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Results<br />
For the 10-year period, 1971 to t980, among 1919<br />
cases of primary <strong>lung</strong> <strong>cancer</strong> in men . 37 (1 .9%) occurred<br />
in validated nonsmokers . Among 749 <strong>lung</strong> <strong>cancer</strong> cases<br />
in women, 97 (13 .0%) were vYlidated nonsmokers, This<br />
difference in the proportion of nonsmokers in men and<br />
women is hiittly statistically sipifiant. X2(1) - 137 .21,<br />
P
1216<br />
C.wcfn March 1 1984 vai . 33<br />
TAu.f 2 . Dutnbuuon of IIursround vuiables hold for both KteyberY I and Kreyberg 11 types : the man<br />
in Castes tnd Convoli<br />
age for Kreybcrg I and Kreyberg 11 <strong>lung</strong> <strong>cancer</strong> in men<br />
Me n W omen<br />
c. ... c.. UIQ4 c..a cow U-CAS<br />
was 52 .8 and 53 .6 yars, respertively, while in women<br />
Kreyberg I had a mean age of 63 .7, and Knyberg II had<br />
a mean of 61 .0 years.<br />
(No,) (R) (W-1 W Rro .) (*) (No .) (i6)<br />
Age<br />
zs9 13 (35) 12 (32) 12 (12) Is (IS)<br />
l0-S9 11 (70) (2 (32) 26 (27) 24 (2S)<br />
i0 .•69 7 Q2) 10 07) 21 (30) 34 (~s)<br />
70. 6 (14) 3 (l) 30 (31) 24 (25)<br />
Teu! 37 37 !7 97<br />
RAfipo n<br />
hamani 2 (6) s (I4) 27 (211 34 (36)<br />
Cttnol,c 16 (46) 14 /s0) 31 (32) 36 ()1)<br />
Jrnsh Is (43) U (31) 3t (40) 24 (27)<br />
ou,n 2(u 3 (9) 0 (0) I (u<br />
TouJ 33 33 ~6 *b<br />
Yr ot .ducation<br />
1-II 3 (14) # ((6 .Z) 31 (392) 29 (299)<br />
12 7 (l6 .2) 11 (297) 23 (271) 31 (341)<br />
(3--IS 6 (21 .A) 1 (216) 14 (lS .!) 17 (lS .S)<br />
16+ 20 (u .1) 12 (324) 16 (17 ..7) Is (ls .s)<br />
Totil 77 37 97 +7<br />
Qxvp.ua+al auw<br />
t•raka,aul 22 (39 .s) 14 (318) i (L2) 11 (1I .3)<br />
slulkd 6 (11 .2) 7 (11 .9) 26 (21,U 33 (36J)<br />
SrmuJ
I<br />
hi4 5 LUNG CANCER 1N NONSMOKERS - Kabar and Wyndef 1217<br />
btr of ycars of <strong>exposure</strong> in textile-related jobs (16 years)<br />
of cases and controls Among the cases, the specific occupations<br />
were the following : one seamstrrss, two dressmakers<br />
. one sewing-machine operator . one assembler and<br />
yarnwinder . one dress-shop worker, two salesladies who<br />
had done factory work, one apparel manufacturer, one<br />
clothing packer, one typist, one washerette/housekeeper,<br />
one bookkeeper, and one housewife .<br />
Among the 37 male cases only a few (5) rrpotteG <strong>exposure</strong>s<br />
to substa.nces of potentially etiologic interest. An<br />
electronics engineer had 35 years of <strong>exposure</strong> to cleaning<br />
chemicals: a designer had 25 years of <strong>exposure</strong> to chemials<br />
and acids and I S years of <strong>exposure</strong> to plastics and<br />
glues ; a director of sales for a chemical corporation (a<br />
chemist) had 12 years of <strong>exposure</strong> to chemicals and acids ;<br />
an upholsterer had 30 years of <strong>exposure</strong> to asbestos, rubber<br />
. and solvents ; and a machine shop attendant had 37<br />
years of <strong>exposure</strong> to metals . grease .'and oil .<br />
Among the 97 female cases, in addition to <strong>exposure</strong><br />
to textile work reported by 14, few reported other <strong>exposure</strong>s<br />
. The assembler/yarnwinder who reported <strong>exposure</strong><br />
to textiles also reported <strong>exposure</strong> to metals for 28<br />
years ; a machine operator had 10 years of exposurti to<br />
tnetals; an assistant medical technicjan had 10 years of<br />
<strong>exposure</strong> to chemicals and acids ; a social worker had 5<br />
years of <strong>exposure</strong> to metals and welding~ art electronic<br />
prototype technician had 14 years of <strong>exposure</strong> to chetnials<br />
and acids, metals and solvents ; and a chambermaid<br />
had 23 years of <strong>exposure</strong> to ammonia .<br />
We looked separately at the small number of ases who<br />
developed <strong>lung</strong> <strong>cancer</strong> younger than age 40, eight men<br />
and six women . The occupations of the men included<br />
an accounting professor, an accounting clerk (who had<br />
been a teacher for 11 years), a neurosurgeon . a stock<br />
trader, a postal service clerk, a law student, a salesman,<br />
and a self-employed president of a supply company . None<br />
of the men reported any <strong>exposure</strong>s . The female cases<br />
included two houscwives, an assistant mana ;er for the<br />
Ametia .n Automobile Association, an electronic prototype<br />
engineer (mentioned above), a telephone operator,<br />
and a high school teacher . Only the electronic prototype<br />
en=ineer reported any <strong>exposure</strong>s . The distnbution of histologic<br />
types among these younger pses did not appear<br />
to differ from that of all nonsmokin= cases .<br />
Passive inhalarion : Of the 25 male ases and controls<br />
who wexe asked about <strong>exposure</strong> to other peopie's ciprette<br />
smoke at home, six male ases reported having been exposed<br />
compared to $controls (Table 3) . Eighteen of 25<br />
cases reported having been exposed to cirarette smoke<br />
at work compared to 1I of 25 controls,'Ttte difference<br />
ie just stuistically sirnihcant (P - 0 .05). Mantel extension<br />
test for linear trend in the frequency of <strong>exposure</strong> (four<br />
levels) in cases and controls gives a chi-square of 2 .88, P<br />
< 0 .005 . The number of male ases and controls who<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
TAtt..E 3, Exposure to tassive Inhalatton Arnon{ a Subw<br />
of Cua and Controls<br />
Men Womer,<br />
Casa Controls Cucs Controls<br />
(No ) (S) (No .) (S) (No.) f %) (No .) (ti)<br />
At homc'<br />
Yu 6 5 16 17<br />
No 19 20 37 36<br />
Tout 25 25 53 53<br />
At workt<br />
Yes It tl 26 31<br />
No 7 14 27 22<br />
Tou) 25 23 53 53<br />
(P < 00-45)<br />
Spouse smokej<br />
Ever 5 5 13 15<br />
Never 7 7 II t0<br />
Total 12 12 24 25<br />
' Current e>
1218 CANCER March 1 1984 va 53<br />
our computer file of self-reported never-smokess, review<br />
of the hospital chart revealed that 13 were actually smokers<br />
or had smoked at some time, and 9 were not primary<br />
<strong>lung</strong> <strong>cancer</strong>s. These 22 cases were excluded from the anal .•<br />
ysis . Confirmation of the diagnosis and nonsmoker status<br />
of the controls was carried out in the sime way as for<br />
the cases . For none of the controls was the self-reported<br />
nonsmoking status contradicted by information in the<br />
c3tan .<br />
The finding that more cases rave a conflicdng response<br />
on whether or not they had ever smoked than controls<br />
( 13 of 147 primary <strong>lung</strong> <strong>cancer</strong> cases compared to none<br />
of 134 controls) is of significance . This suggests that some<br />
<strong>lung</strong> <strong>cancer</strong> cases tend to deny a smoking history more<br />
than controls with non-tobacco-related diseases. In a study<br />
of the role of ciprette smoking in <strong>lung</strong> <strong>cancer</strong>, such denial<br />
of cigarette consumption or under-reporting, which may<br />
also take place, would tend to reduce the estimate of the<br />
relative risk . In a study of <strong>lung</strong> <strong>cancer</strong> in nonsmokers,<br />
the inclusion of cases with a smoking history (misclassification)<br />
would also reduce associations of the disease<br />
with other risk factors .<br />
Although we attempted to eliminate all smokers from<br />
among the cases and controls by using a conservative<br />
definition of nonsmoker and by excluding any subject<br />
with a history of smoking either in the questionnaire or<br />
in the hospital chart, it is possible that some subjecu who<br />
rrported never havine smoked actually did smoke at some<br />
time .<br />
The current study confirms earlier findings that among<br />
tifelonQ nonsmokers <strong>lung</strong> <strong>cancer</strong> is exceedingly rare, and<br />
that the more conservative the definition of nonsmoker<br />
and the more detailed the smoking history, the lower is<br />
the proportion of nonsmokers found among <strong>lung</strong> <strong>cancer</strong><br />
cases.3<br />
Histologic Type<br />
As found in earlier studies, Kreybery type 11 (primarily<br />
adenocarcinoma) is more common in nonsmokers with<br />
<strong>lung</strong> <strong>cancer</strong> than in smokers and, in both groups, KrryberY<br />
type 11 is more common in women . The percentages of<br />
nonsmoking cases with adenocarcinoma in our study<br />
(43% of males, 62% of females) arr in close agreement<br />
with those from the American Cancer Society's prospecdve<br />
study (46% of males, 59% of fernales, L . Garfinkel,<br />
personal communication, 1982) . In view of the differences<br />
in design and method of selection of subjecu, this a ;rrement<br />
suggests that these percentages may be representative<br />
of nonsmoking <strong>lung</strong> <strong>cancer</strong> ases generally .<br />
Sex Ratia<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
In our nonsmoking cases there are 2 .6 times as many<br />
females as males, even though the male-female incidence<br />
ratio for lua& ancer is 2 .4,'° and the male-fetnale ratio<br />
among all <strong>lung</strong> <strong>cancer</strong> cases in our file is 2 .6 (1919/749) .<br />
The larger number of nonsmoking women with <strong>lung</strong> <strong>cancer</strong><br />
compared with nonsmoking men is presumably due<br />
to the h.istoricaliy higher proportion of nonsmoken amonQ<br />
women compared to men . Doll found no difierence in<br />
the age-specific death rate from <strong>lung</strong> <strong>cancer</strong> among nonsmoking<br />
males and femalea.' Similatiy, C'rarfinkel" found<br />
no difference in the age-adjusted <strong>lung</strong> <strong>cancer</strong> mortality<br />
rate for nonsmoking men and women .<br />
Case-Control Cornpartsons<br />
Prrvious dueascs : Our finding that female ases had<br />
a hi;her frequency of previous history of pneumonia<br />
compared to controls is difficult to interpret since we do<br />
not have information on the age at diagnosis or on the<br />
duration of pneumonia .<br />
Occuparion Earlier ease studies of <strong>lung</strong> <strong>cancer</strong> in nonsmokers<br />
have included occupations in males with txposure<br />
to dust and/or fumes, i .e ., a carpenter, a joiner,<br />
a fitter, and a pour miller among the 7 male cases in<br />
Doll's study ;' two painters, a smelter, a blacksmith, a<br />
gasoline truck driver, agasoline and oil delivery man and<br />
gas station attendant, a cabinet maker, a sawmill worker .<br />
and an engineer among 20 male ases in Wynder's study;=<br />
a plumber/sitamfitter and an auto body and fender repairman<br />
among 8 male cases in the study by Wynder<br />
and Berg .' Among female ases, the occupations wcrs<br />
leis smestive of <strong>exposure</strong> to inhaled subsunces . These<br />
studies interviewed small numbers of nonsmoking ases,<br />
and did not make use of a comparison group .<br />
Our findings of a suti .stically significant threefold excts :<br />
risk of <strong>lung</strong> <strong>cancer</strong> among women who reported having<br />
worked in the textile industry is of interest . Doll, in his<br />
study of <strong>lung</strong> <strong>cancer</strong> among nonsmokers, lists occupations<br />
of more than 3 yeats duration in 7 male and 40 female<br />
<strong>lung</strong> <strong>cancer</strong> cases . Out of 31 women who had been em<br />
ployed outside the home, 5 had worked as seamstrrsse ;<br />
or dressmakers .'<br />
However, therc is no clear relationship in our dat ;<br />
between duration of <strong>exposure</strong> and risk of disease . Thc<br />
mean number of years of <strong>exposure</strong> was the same for cascand<br />
controls. Most importantly, it is not clear that ther(<br />
is a single <strong>exposure</strong> or group of <strong>exposure</strong>s that all of the<br />
workers in textile-related jobs have in common .<br />
Furthermore, it should be emphasized that our o0<br />
cupational data are limited since there was room only tc<br />
code one occupation-,that of longest duration-and twc ~<br />
<strong>exposure</strong>s . Occupational and environmental <strong>exposure</strong>s tc C<br />
specific substances were obtained by asking the subje,=N<br />
whether they had ever been exposed for more than a yea•~c<br />
to any of a list of substances . Self-reported <strong>exposure</strong>s o .Q<br />
this kind are subject to information bias since awarenes,(A<br />
of such <strong>exposure</strong> could be expected to vary with the in},<br />
~<br />
~<br />
N
No S LUNG CANCER 1N NONSMOKERS • Kabai and WwfdCr 1219<br />
dividual, with educational level, with different }obs, and<br />
between cases and conuols . In only 7 of the 14 cases did<br />
the coded occupation mention textile work . The remaining<br />
seven ases reported occupations not specifically<br />
associated with textiles, such as "typist," but reported<br />
<strong>exposure</strong> to textiles . Evidence from existing occupational<br />
studies of <strong>lung</strong> <strong>cancer</strong> risk in textile workers is<br />
scanL'3-" No cahon study of textile workers appears to<br />
have been a.rried out.<br />
The apparently minor role of occupational <strong>exposure</strong>s<br />
in our male cases is consistent with the high peranta ;e<br />
of professionaLs (60%) among them . Altbough our data<br />
do not suggest an important role of occupation or <strong>exposure</strong><br />
to specific substanca, it .vould be desirable in the<br />
future to obtain more detailed and objective occupational<br />
histories on cases of <strong>lung</strong> <strong>cancer</strong> occurring in nonsrnokers .<br />
Passive inAalation The plausibility of a role of passive<br />
inhalation in <strong>lung</strong> ancer can be questioned on several<br />
frounds . Although sidestrcam cigarette smoke contains<br />
higher concentrations of toxic components than mainstream<br />
smoke," it is diluted in the ambient air to varying<br />
degrees (depending on the size and shape of the room,<br />
proximity to the smoker, and ventilation) by the time it<br />
reaches the passively exposed person . As shown by Auerbach<br />
and coworkers," the changes in the bronchial epithelium<br />
characteristic of smokers are rarely observed in<br />
lifetime nonsmokers .<br />
Nevertheleis, the possibility that havy <strong>exposure</strong> to<br />
secondhand smoke over a long period of time could lead<br />
to increased <strong>cancer</strong> risk cannot be ruled out at prescnt .<br />
8ecause questions on passive inhalation were introduced<br />
in our questaonnaire in 1978, we only have information<br />
on this factor for between 28% and 68% of our subjects<br />
depending on the specific question . We present the distributions<br />
of responses to these questions as preliminary<br />
data since the numbers are small . Cases do not differ<br />
from controls except for the greater <strong>exposure</strong> to eijaretu<br />
smoke at work reported by male cases compared to male<br />
controls. Those cases who reported passive inhalation<br />
<strong>exposure</strong> did not differ in their distribution of histolotic<br />
types from unexposed cases . The ditference between <strong>exposure</strong><br />
to ciprette smoke at work between male cases<br />
and eontxvis could be due to information bias, althoujh<br />
there is no indication of such bias in the responses to the<br />
other questions on passive inhalation .<br />
The studies which, to date, have addresssd the issue<br />
of passive inhalation and <strong>lung</strong> <strong>cancer</strong> have differed in<br />
methodology, the population studied, the type of <strong>lung</strong><br />
<strong>cancer</strong> studied, the degree of histologic confirmation, and<br />
in results . These studies are summarized in Table 4 . They<br />
have been commented on by a number of investiptors<br />
." ."''• We wish to draw attention here to several<br />
poinu which are crucial in assessinj a eontribution of<br />
passive smoking to <strong>lung</strong> <strong>cancer</strong> and which need to be<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
considered in future studies . First, the proportion of histologically<br />
confirmed diagnoses in the studies listed in<br />
Table 4 ranged from 35% (Trichopoulos a al (2G)) to<br />
82% (Chan and FunQ 1211) . Given the difficulty of diajnosing<br />
<strong>lung</strong> <strong>cancer</strong>, histologic confirmation is essent .ia).<br />
Second, Trichopoulos et al .i0 excluded adenocarrinoma<br />
and terminal bronchiolarcases, whereas adenocarcinom3<br />
predominated in Hirayama's easesu (personal commuttication,<br />
1981), in those of Chan and Futt=,2' and in our<br />
csses . In the American Cancer Society study reported by<br />
Garfinkel," histologic type was obtained for <strong>lung</strong> <strong>cancer</strong><br />
cases during the first 6 of 12 years of the study . Seventy<br />
percent of these nses had histotofic confirmation but<br />
some of these were only identified as "arcinoma." Among<br />
the ases with confirmed histology and information on<br />
specific cell type, 46% of the male and 59% of female<br />
nonsmokers had adenocarcinoma compared to 23%<br />
among male and 46% among female smokers (personal<br />
communication) . Since tittle is known about the etiologic<br />
significance of different histologic xypes and since the<br />
distribution of types differs in different populations, it is<br />
premature to restrzct studies of passive inhalation to particular<br />
types .<br />
Third, although histologic classification of <strong>lung</strong> <strong>cancer</strong><br />
is imperfect, it is desirable to stratify by the major histologic<br />
types in the analysis if the number of cases permits<br />
since differtnt histologic types may have different etiologies<br />
.<br />
Finally, all of the previous studies used the amount<br />
and duration of spouse's smoking as the measure of <strong>exposure</strong><br />
to passive inhalation . Focus on the spouse's smokin;<br />
may fail to provide an adequate measure of the subject's<br />
<strong>exposure</strong> for a number of reasons : (1) a subject's<br />
actual <strong>exposure</strong> depends on how much time the smoking<br />
spouse smokes in his or her immediate presence ; the<br />
spouse could be a heavy smoker but spend very little<br />
time at home ; (2) in addition to the current spouse's<br />
smoking habits, those of former spouses may be equally<br />
important; (3) the subject may live with other relatives<br />
who smoke ; (4) <strong>exposure</strong> to tobacco smoke at work can<br />
be a substantial proportion of a person's <strong>exposure</strong> ; (5)<br />
<strong>exposure</strong> in cYSS, tommuter trains, buses, and in other<br />
situations, such as restaurants, movie theaters, etc, eould<br />
be sitnificxnt It is for these reasons that we have recently<br />
revised our questionnaire to include detailed questions<br />
which will give a more complete picture of the subject's<br />
<strong>exposure</strong>, both in respect to diffcrent environmental aettings<br />
and to duration of <strong>exposure</strong> for each specific component<br />
.<br />
If passive inhalation in nonsmokers is associated with<br />
increased <strong>lung</strong> <strong>cancer</strong> risk, by what mechanism does it<br />
exen its effect? Since adenocarcinoma is the most common<br />
histologic type of <strong>lung</strong> <strong>cancer</strong> in nonsmokers, one<br />
could hypothesize that inhaled sidesttram smoke increases
,<br />
1220<br />
GNCER March 1 1984<br />
TaaLE 4 . Summary of Studia of the Rolc of Rsssslve Inhatation in Lung Canccr in NonSmoken<br />
Author/<br />
type of siudy/<br />
population No of asss Histology<br />
Hiryyama (t9a1 174 datlu in marncd Out of a sampk of 23 aaes_<br />
fropecu .t/ r«oaxnoicia` .roenen 17 were adenoarrieoma<br />
lap.nesc w/)unb a amonj<br />
twnsmo k i n6 9 I .340 nonszrtokt nt<br />
..iva atKd 40+ wrr+ed +oomen<br />
yClan<br />
Garfinkel (19{l)" 195 daths from <strong>lung</strong> a<br />
Analytis oa dlta among male<br />
from two twnsmokers: 56A<br />
pxospmtve daths from <strong>lung</strong> a<br />
txudies/ACS among female<br />
population and tsonamolcen (ACS) :<br />
Dom study of 168 <strong>lung</strong> a deaths<br />
vetersns" among nonsmokers<br />
(Dorn)<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Histdots SC . Ho HC, lronthial aaar in<br />
the risk for this type. Volatile components of cigarette<br />
smoke, including volatile nitrasamines, are more likely<br />
than respirable particulate nutter to reach the periphery<br />
of the <strong>lung</strong> . Current 6ndings suggest most lesions in nonsmokers<br />
are located in the deeper portions of the <strong>lung</strong> .<br />
Nonsmokers exposed to ciprette smoke in enclosed<br />
spaca are reported to have increased levels of carbon<br />
monoxide in their blood,"2s which su=esu that other<br />
F'indinfs<br />
A dae-rssyonae esiatiooshtp<br />
.as aten herwven the<br />
iocttmoking wivts' titah<br />
aad ahe kustxnds'<br />
amokirtr Mab(t wives of<br />
tatenoktn or of 1-19<br />
dss/day-unokers bad RR<br />
- 1 .61 : Wi .a ot unoken<br />
of a20 eies/day had RR<br />
•2.0b<br />
No aigni6cant iactsax in<br />
lun/aftskfeenin<br />
aasnmokinb wi .es of<br />
amoking husbands<br />
compared with<br />
aonsmokintt wlvss of<br />
monsmokink hustxnds<br />
RR of <strong>lung</strong> a associnted w/<br />
Mayin= a husb.nd who<br />
nrtsokes 1 pock/day wu<br />
) .4 . (xt for linear trend<br />
• 6 .45 : P < 0.021<br />
Amon4 t+onsmokins women<br />
the prnponton of ases<br />
whwe >tpouae tunoked<br />
was slightl,v krwer than<br />
that o(contro(s (34 of 64<br />
or40 .S1,n66of139or<br />
47 .3%). Among<br />
aonsmokin ; women .<br />
there was no aqnificant<br />
diRettnce in the<br />
proponion of ases who<br />
wed kernoene fueltn<br />
Cookin; compared with<br />
tontzols<br />
Hotit Kong 1976-1977, Ir J Csnct* 1979 : I9 :1t2-t92 .<br />
Commenu<br />
Exposurc tadcx was,<br />
based oa tmok nt<br />
hab+u of husband :<br />
Exposure index wu<br />
duad on smok nt<br />
habtts of husbanG .<br />
Exposurc tnbex was<br />
brxd od unottn4<br />
ha.biu of kusMnds<br />
and former<br />
husbands<br />
It is uncku what<br />
quesuon .as uied<br />
feprdins<br />
inhatauon since in<br />
an earlier p.peY .<br />
the quesuon it<br />
pren at'Art you<br />
exposed to the<br />
tob.eeo smoke of<br />
oehen u Mome or<br />
at wo .k?' ;<br />
whCrru here<br />
reference is madc<br />
only to -smoktnt<br />
Mabiu of spouus "<br />
No tnformauan ts<br />
yven on how<br />
many sub~etta<br />
wors tturned<br />
N<br />
volatile components could reach the lunii . It would be C<br />
important to know in this regard whether the loation o!n<br />
lesions in the <strong>lung</strong>s of nonsmoking <strong>lung</strong> <strong>cancer</strong> cascs with C4<br />
<strong>exposure</strong> to passive inhalation differs from that amone(Z<br />
smokers. ' CA<br />
In addition to the etiologic factors discussed in this}A<br />
artick, other possible explanations of the occurrence ofCA<br />
<strong>lung</strong> <strong>cancer</strong> in nonsmokers should also be considered .0<br />
W
t<br />
Exposure to ionizing radiation in the course of radiation<br />
tre.atment could be responsible for some caxs . Also,<br />
Auerbach and cvworkers28 have suegested that <strong>lung</strong> <strong>cancer</strong><br />
could arise in nonsmokers secondary to hei.led tubercuiosis<br />
sraas, althou¢h this is unlikely to atcount for many<br />
cases.z' Another possibility is that <strong>lung</strong> <strong>cancer</strong> in nonsmokers,<br />
es ;xcially adenocarcinoma, is estroQen-related<br />
since it is more common in women than in men . It has<br />
been shovm that adenocarcinoma of the <strong>lung</strong> frequentty<br />
conttins estrogen r>:ceptors .n Still another possibility is<br />
that a.rcinoQr.ns of nutritional origin could be carried to<br />
the <strong>lung</strong> by the blood . These possibilities deserve epidemiologic<br />
exploration .<br />
REFERENCES<br />
1 . Dall R, Mortality from <strong>lung</strong> <strong>cancer</strong> among non-smokers . dr J<br />
Cancn 1953,7 :303-12 .<br />
2 . Wynder EL 7obacco u a cause of lunt ancer, with spaial referena<br />
to the infrequency or <strong>lung</strong> <strong>cancer</strong> among non-smoYers . Pennsyavania<br />
Med J 195A ; 57 :1073-1083 .<br />
3 . Wynder EL &rj Jw. Cancer of the <strong>lung</strong> among nonsmokers<br />
Speaiiv referrnee to histoloyc panerns Cancrr 1%7 : 20 :I161-72<br />
4 . Vinant RG . Ptckren 1V.', l .ine WW et a/ The changint histopathololy<br />
oflunY ancer. A review or 1682 cases. Cancer 1977 ; 39 :1617-<br />
1655 .<br />
S . Ru!!x P, Hinch A. Maruau D, btanon J, Chreuan J . Etude ettolapque<br />
et hata4aypue de L4fi etncen du poumon . Ann Med luem<br />
1981 : 132 :12-13 .<br />
6 . Wyndtr EL StelJman SD Comparative eaidernioJogy of tobamc<br />
. Cancn Res 1977 ; 37,4608-4622,<br />
7 . F1nu JL Statisiinl methods for rates and proportions . New York :<br />
lohn Wiiley and Son, 1981 .<br />
1 . Mantel N . Chi-square tests with one dqnx of freedom : E :tension<br />
of the Mantei Hsensul procsGure . J Am Stat Assoc 1%3, 59 :690-700 .<br />
9 Mieninen OS . Ewmability and ewmation in ptt-refcrent saudtcs .<br />
.fm J Epsdemiol 1976 ; 103 :226-235 .<br />
10 . Amuican Canxr Socuty . Facts and F"Kures Chtato : ACS, 199 1 .<br />
11 . Garfinkel L Time trends in lunt anecr monality among nonsmokers<br />
arsd a nou on passwe smokint . J Nml Cancer Insr 1991 ;<br />
66 :1061-1066 .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
LUNG CANCER 1N NONSMOKERS • Kabat and Wynder 1221<br />
.reLted <strong>cancer</strong>s<br />
Vllter Symposium : Lymphomzs<br />
12 . Nhlltamf RR . Stelent NL Goldsmith 1R Auoc-utions of ancer<br />
da arsd typc with oecupatton and induxtry fnam the Third National<br />
Cancer Surey instrvtew, J Nar! Cancer Insr 1977 : 59 .1 I
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
6
Kabat, G .C ., "Epidemiologic Studies of the Relationship Between<br />
Passive Smoking and Lung Cancer," ToxicolocTV Forum, 1990 Annual<br />
Winter Meeting (transcript) : 187-199, 1990 .<br />
In 1990, Kabat reported preliminary results from an<br />
American Health Foundation case-control study, which then included<br />
90 cases and 247 controls . Kabat reported that "preliminary<br />
analyses of the data do not indicate any striking ETS <strong>exposure</strong><br />
differences between cases and controls ." Specifically, he reported<br />
odds ratios for men of 0 .98 (95% CI 0 .46-2 .10) and for women of<br />
1 .00 (0 .49-2 .06), for reported workplace <strong>exposure</strong> . The risk<br />
estimate for males is negative, and that for females is the same as<br />
the baseline, "no-risk" level .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
TOXICOLOGY<br />
FORUM<br />
1990 Annual<br />
Winter Meeting<br />
February 19-21, 1990<br />
L'Enfant Plaza Hotel<br />
Washington, D .C .<br />
JllP; 2 ": 199D
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
1990 A.nnuai Winter To)dcology 1"'orum<br />
L'Enfant Plua Hotcl<br />
Wuhi.agton, D .C .<br />
Fcbruary 19•21, 1990<br />
AJI rtiphn r.wnv*d . No portion 0 thn tranacript may ba r.produsrQ u utiuxsd in any form or try any m.ant .<br />
•Lcuonk or m.duniul, k+dudlrp al.ctorutic or phomoopy{np, rewrdinp, hfonraauon ttvape or r .tr'aval tytumt, or<br />
Oomputart, .fCSout prior parmitsjon In vrrttlnp hwn V* btrd ol Dirtepxa Hf Sh+ TtuJoojoqy Forum .<br />
Wm. ot eh" rtutarWt In C+It tan .artpt m+y bA ar.llabH •L.wh .rt, M+ on tortn or another ; fwwtv.r, M la<br />
avfiltbIt nowhsrt .lu aa K h ananpad Mrain . Akhouph tM ooll.ciiorn antl oompllati~ pl (rtformaUon haf b .an cu .1uuy<br />
pnW .c and r.pra.rrb a aipnlf"nt .mploym.M oI tuft drm aAd r.wurat, t!w ToYiaoloqy Forum Im na rstpor,t~Drt<br />
ior any rut.m.rtp a .rron or omia.lont 1n tn* manuKripa or kn th* tral+ .uipt ;oe+ ei/ tha mord .d pnoasdinpt . t49G<br />
ToxioGoqy Focum, Inc ., 15TS Eyrr CtrNt, N .W ., w 6oot, WaMlnpto~, D .C . la.Y~6 .
CONTENTS<br />
Monday, Fcbruiry 19, 1990 i,<br />
Sessioa I•APPROPRIATEN-7E$S OF ASSUMING LO'A',DOSE I .IN'EARITY<br />
- E,<br />
C)R SECON-DAR)' C_ARCINOGE45<br />
Cbiirman : W . Gary flamm, Scienct Regulitory Syucros Intemational, DC<br />
IMPA t^'f OF ADD1TT1?TY TNEORY TO REGU.LA TORS<br />
Rjcbud Hill, Environmcntil Protect .ion Agcncy, DC 2<br />
DISCUSSION 10<br />
STrlTIST1CA1. ARGUMEh75<br />
Danicl krewsk}~, Hcaltb ind Wc1lue, Canada 11<br />
STA77ST1CtL ARGUMEh7S<br />
Tbomu B . Starr, Environ, VA 21<br />
DISCUSSION<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
131OLOG/C4L ilRGUMEh7S<br />
James A . Swenbcre. Uaiversiry of Nortb Cuolina, Cbapcl 1-iill 3Q<br />
DISCUSSION -05<br />
BIOLOGICAL ARGUMEN7S<br />
R . Micbact McClain, Hofiman•l .a Rocbe, lnc., NJ ' 67<br />
PAN'EL DISCUSSION<br />
Chairman : W . Gary Flamm, Scieacz RcguJator3• Systcros lateraatioai .l, DC<br />
David V+-' . Gaylor, National Ccatcr for ToxicologcaJ Rouuc .h, /,R 62<br />
LUNCHEON SESSION 69<br />
Sess{on 11 ./X1MUM EXPOSED lh'DIY1D 1 r .<br />
Ctuirman : Paul Portncy, Resourcu for t .6c Future, DC 73<br />
GElJER4L CONCEPT'S<br />
Joha Grabam, Harnrd Scbool oi PubGc HcwJth, MA<br />
.<br />
74<br />
t~<br />
GRT77QUE I• PUBLJC HF.rl1.TH PERSPECTTYE<br />
~<br />
Beraud Goldstcin, EcviroameataJ & Occvpu6onsl ~i<br />
Hc .Jtb Sdcoaet lnuitute, NJ 90<br />
Pag=<br />
I<br />
.'.5<br />
GO
CRI77QUE 11 - EXPER1LfEN?A1,ISTS P .r.RSPEC77VE<br />
Aagclo Turturo, Nationtl Ccnter for Toiocological Rcuucl, AR 97<br />
DISCUSSION 101<br />
ASSESSING TNEA.IR TOX7CS PROBLEM USINGAMBIEhT DA TA<br />
Waam Hunt, Envirocmcntil Protc .uioc ~kgcmcy, NC<br />
DISCUSSION<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
NEW LEGISl.4T10N ON .rL1R POLLUTION<br />
Robert Buatrd, Clcary, Gottlieb, Stcen & Hamilton, DC 131<br />
SOME TNDUGNTS ON MEl PR .FD1C77YE EXPOSURF ASSESSMEhTS<br />
Ncil H.wkins, Tbc Dow Cbcmiu] Compnny, MI 1.38<br />
DISCUSSION 153<br />
U<br />
PaEc<br />
148<br />
128
CONTENTS<br />
Tu :sday, Fcbruar} 2 0,<br />
1990<br />
P age<br />
Session I1I - tI E FFF M O h'1v RO*1M DB D-h<br />
Cbairman : Gio B . Gori, HuJtb Poticy Centcr, MD 159<br />
REVIEW OF A WORKSNOP : ASSESSING 1.OW RJSKA GEh7S<br />
FOR LUNG CANCER<br />
Ragnu Rylandcr, Univcrsiry of Gotbcnborg, Swcdcn 159<br />
DISCUSSION<br />
ASSESSMEh7 OF EXPOSURE<br />
Nanry Haley, Amcrican HcAltb Foundatioa, NY 170<br />
DISCUSSION<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
EPIDEMJOLOGJC STUDIES OF THE REUlT1ONSNIP BETuE'EN P.lSSIVE<br />
SMO~JNG .4 ND L UNG CA NCER<br />
Gcoffrcy Y,,.abat, Amcricus Hcaltb Foundation, h'Y 18,<br />
DISCUSSIO?: 2(R?<br />
INYOL Uh7rdRY SMOKING Ai .'D LUNG CANCER<br />
Lavrrcnct Gufiake~ f.merican Csncer Socicry, h'Y 20 .<br />
DISCUSSION 2,^,5<br />
R.ESPIRATORY EFFECTS<br />
Philip Witoritl, Gcorge WisDington UnivtrsSty, DC 209<br />
DISCUSSION 220<br />
XE.iRT DISEASE RISK IN PASSIYE SMOKERS<br />
Daic Saadtcr, Nationil I :nstitutc ot Ecviroamental Hcakb 5c3cnaes, NC 2Z3<br />
DISCUSSION 231<br />
CAR,DIOYASCUL.4R EFFECTS<br />
l .awtcacc M . Wcxler, New York Medical ColJege, NY 2,35<br />
DISCUSSION 2A5 ~<br />
~<br />
~<br />
~<br />
~<br />
~<br />
sv<br />
167<br />
16-i<br />
~<br />
~
Sesstop TV: jIDTECN^tDLQjjT • RFPDRT DF A PEER R`~?<br />
Chairman : Ricbard Ronk, Food and Drug Administration, DC<br />
GENE:R.iL OVERT7EW. TNE PURPOSE AND CONTFh? OF THE IFBC R.EPORT<br />
Richard Hall, lnternational Food Biotechnology Council, DC 3 4 ;-<br />
SAFETYEVALU.lT7ON PROCEDURES IN 7NE IFBC REPORT<br />
lan Munro, Canadian Ccntrc for Torocalopy 232<br />
DISCUSSION<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
ENVIRONMEh?,4L REVIEW OF BIOENGINEERED PRODUCTS<br />
Buzz Hoffman, Food and Drug Administration, DC 268<br />
DISCUSSION 2E3<br />
PR .lCTIG1L . EXPERIENCE IN RFGULfT70N PRODUCT APPROVA .1.<br />
Fred Shank, Food and Drug Ad.ministratioa, DC 2S4<br />
DISCUSSION 291<br />
Pagc<br />
BOVINE SOM..tTOTROPIh' BST/BGH<br />
Gerald B . Gucst, Food "d Drug Administration, MD 295<br />
FOOD SriFETYilSSESSMEh? FOR THE USE OF BST IN DAIRY COWS<br />
Brua Himmond, Monsanto, MO 299<br />
DISCUSSION 316<br />
THE SAFETY OF FOODS DEFtIVED FROM TRANSGENIC AN1AiA1 .S<br />
DsYid Berkowitz, U .S . Dcpartmcnt of Agriculturc, DC 316<br />
DISCUSSION 331<br />
CONSUMER AND CONGRESSIONAL V7EW POINTS<br />
Lesley Russell, Committec on Encrgy and Commcrce,<br />
US . Hotuc of Rcprescatativc4 DC 332<br />
DISCUSSION 335<br />
247<br />
263<br />
~<br />
~<br />
iv ~<br />
~<br />
~<br />
~<br />
~<br />
~<br />
~
Wednesdsy, February 21, 1990<br />
Sessloo V: $FS ATORX,u A S<br />
CONTENTS<br />
Cluirmaa ; Robert 7 . Scheuplcin, Food aad Drug A .dmia.istration, DC<br />
PD& C R.ED 3<br />
Roben J Scbcuplcin, Food a.nd Drug hd.miaistration, DC 337<br />
DISCUSSION<br />
DIOXIh' IN PAPER PRODUCTS<br />
Dwain L . k'intcrs, Env'uonmcntal Protection s.gency, DC 3-1,0<br />
DISCUSSION<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
PROFOSTT7ON 63<br />
L.aureo Zcisc, Department of Ncalth, CA 349<br />
DISCUSSION 354<br />
NC! UPDr(T'E ON !Q (2•AMINO-3-METHYL.IMIDr1ZO (4,5-F) QUtNOLINE')<br />
Richa.rd Adamson, NatiooaJ G.aur ]nstitute, MD 357<br />
DISCUSSION 363<br />
RISKriSSESSMEh7AND TN£ Fi'rtXM.tNPEST7CIDE BILL<br />
Mikc Taylor, King & Spa]ding, DC 367<br />
DISCUSSION 371<br />
THE BENZENE DECISION<br />
Jeanette Wiltu, Environmental Protcction Agency, DC 373<br />
DISCUSSION 3g8<br />
v<br />
Pagt<br />
337<br />
339<br />
345
DR, KABAT : Thaak you .<br />
The problem of pusive smoki4 and <strong>lung</strong> eaneer hu provoked a good deal of debste botk<br />
on a scicntific tnd on a public poliry level, Do the ctud ;es tlut purpon to sbou am assoei~tioa of<br />
<strong>exposure</strong> to environments] tobacco smoke (ETS) snd <strong>lung</strong> caneer occurring in lifetime aotumokers<br />
providc adequate evidcnce to resalvc the issue? As Naacy Haley has just ebo ..rs, zbc and bet<br />
eollca.gues s.re very good at measuring recent ezpcswc to ETS uuing eotinine measured in etliva,<br />
serum, and u,rine . Unfortunately, tbcsc biomarkers ue not belpfiil for asscssia~ <strong>exposure</strong> over tbc<br />
sevcril deeades relevant to tbe induuion of lun .g ea.ncer . Given the lack of a biomuker for loagtcrzo<br />
ezposure to ETS, epidemiologic stvdies havc had to rely on ssl!•reporu or prozy•repQrts of<br />
ETS czpc>stuc .<br />
I propose to raist F hat I eonsidcr to be some of tbe key aspects of the roujlJ ; IS<br />
epidcmiologc stud.ics of tbe iuuc of ETS and fu .mg <strong>cancer</strong> and to poi.at out eertain ueu t.b : : rcqu!- :<br />
furtber study . I Mill I-iefl} refer to our owm study ..,hicb is sti.lJ in proYress at tbe Amcri :a: Hca: :~<br />
Fou.ndation . FAnall), i wilJ stsggcst a possible d'ueaion for furtber stud7 of tbis iscuc .<br />
EPIDE1.ilOLOGIC<br />
Table 1 lists studies cumi .t:inE tbc <strong>lung</strong> eafleer risk of non•s .mokiag vrivcs of smok.ing<br />
btubi.nds eoWpued to the non•smoking wives of noo•smol ;iag busbinds . One notes tbat tbe<br />
grutest ms ;zitude of thc overall relative risk (RR) is 2 .1 . A .fter the Tricboposilos and Correa<br />
aud;es, the higbest RR is 1 .65 (Laas et al ) . The national Reseueb Couneil's committee on pusi%c<br />
smoking earricd our a meta-anaJysis of tbc erist.iag uud.ics in 1986 and eame up .ritb am overall RR<br />
of 134 (95e"ro eonfidenee inten•al 1 .18•1S3) (1) .<br />
In four out of the fu`teeo studies listcd, the overall RR is etatistiesll} tigaif~cani . 1A'bcn<br />
onc exuaines the diti by level of ezposurc, i .e ., aumber of eiguenes ptr day emoked by the<br />
husbi.nd slratified into two or more levels, 8 of the 15 ,studies sbow evidence of a dou•response<br />
rclatiotubip,<br />
MSTOLOGY<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Wben we look at tbc eftect of ETS <strong>exposure</strong> by histologic type, wn sts an interesting<br />
disaepttnry (Table 2) . Dalager et al . (2) and Pershagee et al . (3) sbow roughly eompsrably elevated<br />
odds ratios (OR) for squi~mous oeU and emaU ecll cuanomu eambines, but not for<br />
adenocua.noma . In eontJast, Lam et a1 . (4) obuined a sigaiftcant eI(ctt for adcaor.arinomr+ but not<br />
for squamosu cell eucinoma .<br />
Tbe rtsulu of Hir .yama's atudy (5) prestunably agee on this point .vitb those of l,am et<br />
a1., sioce the majority of bis lu,j eatnacr ease .s +s+erc apparently adcnocareinoma . . Tricbopoulos et al<br />
restslts (6) prestuaably wtigb in on Ibe side of Dalagcr e1 al . asd Pers2sagyn et al, since<br />
Tric,bopouloc s :clude.d adenocxrizoma and term .iaaJ brme6ia) zuciaocsa from t}seir aeries .<br />
Since adenocariaoma oceurs morc eommon}y 'sa never amokers thia ba smokers snd<br />
rencrally more cammoa}y in .romen than ia men (7), oat wotild ezpect t2tat itf .FI'S ezocxurc is an<br />
appreelable risk factor tor hm ; aaa.r, it is auooiate .d w?it.b sdenocudssoma, as wtll as posS.r'bly vritb<br />
o6er types . 'I1e ina>asiuenry ia the results to dule regardi.ng Li.uoloLy iadieates that tLis is one<br />
uea thit merus furtber uudy.<br />
297
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
ASSE$SMEh? OF DISEASE STATUS<br />
MisclissiGcation on diuase uatus occurs wbce diaposcs otber t .ban prinn cxscinotri of<br />
tbe luag are induded in tbe easc series or .rbeo a primary eancer of tbe lubg is iucluded among tbc<br />
contsols due to iu ksaviag 6one uadcteaed Garftakcl et &i . reponed that of 283 .+omcn listcd as<br />
luving lu.ag ea,nar in bospita, rteords but sritb no mention of tDeir having r .n;,aked, 36 (12 .")rc)<br />
tvrncd out to b.avc diWoeet oeber tbin Iuag eaacer wbcn the histologv .ras reviee+ed by one of thc<br />
autisors (8) .<br />
ln uud.ies in whicb kiixtotooc vcritieation of lt,tng ea .oeer is a eriterion for indusion in tbe<br />
srudy, mi«liccifiution tbould bx minimaJ . Nov~rcvcr, tiomc of tbe uudies listed in Table 1 wcrc<br />
lsc.king this for all cucs .<br />
lt sbouild a1so bc mcntioncd that ev=a vbca luag a.ncer is biuologacally veriftcd, it is<br />
posssble that t:omc eases judgcd to b~e pr~mary sa.nc.er of tbe <strong>lung</strong> arc aaually r~eeoadary io a cay :cr<br />
of anotber sitc that bas gonc undete.ued<br />
ASSF_SSMEhT OF E?t-FOSURP STATUS<br />
This is a geater problcm tbas asussment of discasc status, and for somc i .nvestigators it<br />
is tbc key problem of epidcmiofogic ctud .ies of ETS a.ad luag eanccr (9,10) .<br />
Misclassi.ficat .ion of esposure szatus un occur in a Aumbcr of ways . F'ust, subjects p~o<br />
bsvc t;mokcd for s.omc period of thcis lifc c.in be erroncously iacluded in a t;tudy of tacver smokcrs<br />
Se .cond, subjcas may uadcr•repon (minimize) or over•repon (inllate) tbcir ETS exposusc, or this<br />
may be done by proxies . A t.isird type of misrlassifrcauon ean occur .rben trome iadireu measu : c<br />
(zucb as .rbcther tbc subjea is maNied to a smoker or bow mucb t4sc spouse amokes) is tued as a :z<br />
iadicator of ETS <strong>exposure</strong> . The cffect of misclassificution oe abe estirnate of tbe RR depends on<br />
Wbctbcr thc m'tsclassification is random or diffcrcntia) (tbat is tystcmatic) . Random misdissiTic•a ;ion<br />
wilJ bias tbc estimate of tbe RR towud tbe taul .l, thus making an eFfeu, if tbere is one, more d ;uicult<br />
to dcteu . If misrJassifieation oa ezposurc differs ber*'cte eases asd eoatrols, tbe estimste of the RR<br />
ca.n be bi.ased eitbcr upwuds or dovrnwards dcpendiag on the d'ueuion of t .bc bi.as (11) .<br />
MLSclGJS(fica.rion of Acr1vC sr/loktrl a.t f1CYtr Jrrloklr3 .<br />
Garfinkcl and eo- .+orkers found that among <strong>lung</strong> eancer w .es ideatiTed as 'saonsmokcrs'<br />
or lacki.ng aay mention of t:moking in the bospital reeord, 40% vcrc revule.d to have smokcd up, n<br />
reinterview (8) . AJtbougb a detailed persana] interview yields more acGwatc ssnokiag histories tba:<br />
reliince on bospital ebarts, it is sti11 likcly that, evtn .+bcn eubjc= are diruxly intenicwcd and morc<br />
w*?bca various prwoes ase ttud, aomc miulsssification of ttmokers as ootumokers Dccurs .<br />
Let his argued that random misrlassificatioa of emokers as aoa•uaokers eouple .d witL a<br />
tendcnry of t:mokcrs to marry tsmokers eould account for the obscrved usocat .ion of aspousc's<br />
znoking and iace .ascd <strong>lung</strong> canr:er risk in non•smoking :pouses (9) . Lssuming a SCr<br />
ci •t~~~__iFiution of amok.ing subje.cts, a RR of 2D for aa .ivc smoking„ no truc eficct of passivc<br />
tmol`in& and a betwcen•tpotuc tmoking concordance of 3,
,<br />
Nuclassificorion of iclf•nponrd ETS rrposvre .<br />
fA study by Pron et a1 (12) suggcsts that mi .sclaisification of sell•reporrtcd ETS expbsurc<br />
may bc esaensivc . They examined tbc reGabiliry of ruponscs in 117 coatrol subjects who had<br />
puticipatcd in a study of pauive s .moking aad who "rc reinterticwc.d on average ciu. months later .<br />
Rcspon.ses to an initiaJ quesiion about ez;osurc to ETS (yes/no) wzrc morc rcliable for <strong>exposure</strong> a :<br />
bome than at work (Table 3) . Rcproducbility of quutions conxraing <strong>exposure</strong> to a spouse's smol .c<br />
(ycs/ao) .+as hith for bot.h szxts, .+ith the rel'ubiliry bein,Y generahy lower for otber (ami)y membcrs<br />
Quantiuuvt mcuures of ETS exposurc, Le, ntssnber "d duration of eacposures, .+erc genera-ll) less<br />
rcliable tha.n qualitativc (or dJcbotomous) mc.uures . In tcneral, non•smokers gave morc reliable<br />
iaformauon on ala parametcrs of ETS expostuc than tmokers .<br />
Unfortunatcly Lbc study by Pron et al, did no( ezamine the rcliabiliry of responses amoct<br />
rsscs u .reli as among controls . ln use•control uudiu part .icululy onc must be conccrveH that th :<br />
cisc's reporiing of cxposufe may be ialluenccd by his dia;mosis . in a study of <strong>lung</strong> canccr ouurri : t<br />
in non•smokers, this could takc the form of uses probing past <strong>exposure</strong>s more intensively thas<br />
controls and ovcr•rcporting crposures to ETS, since some cases mxy feel compclled to find a .=<br />
czplanation for thcir diseasc . On tbc other h&nd, it is also po-uiblc that uses migDt minimiu thc ;r<br />
cxposures out of am unv .illi.ngncss to blame a spousc .<br />
Nuclissificarton duc to use the spouse'i trnob'ng hAbis .<br />
Using the presenc.c of a uaoking spouse as aD indicator of ETS <strong>exposure</strong> can lead to<br />
serious misr.tassif,cation of czposure . Based on a survey of neuly 3$,000 nevcr• and ex-smokers,<br />
Friedman et a1 . (13) reported that tbc seasitivity aad sperificity, of usin .g the prescnce of a cmok .inE<br />
spouse as a prcdiaor of actua) ETS exposurc .rerc quire poor . TD.irrynine percent of tacn and a7r;;<br />
of womeL married to smokcrs reponed zrro bours of <strong>exposure</strong> at home . Conversely,,9ric of mcn<br />
a.nd 41 % of women married to non•tasokers rcportcd aome ETS cxpostuc .<br />
COT.'POUTr'DING<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Confound.ing is another major problcm arex for the evaluation of epidemiologic studics of<br />
ETS and luag <strong>cancer</strong> and one tbat has reczivcd relativcly littlc attcntion .<br />
Scvera7 studies :uggest that a Yariety of factors could aa as cosfouadcrs of am ETS•lu .nE<br />
<strong>cancer</strong> tssooiaiion . Friedma.n (13) found that agc bore a urocg neptivc rclationship to rcponed<br />
It:.TS expostue . Hours per vicek of ETS expc,stut .vere associatcd with alcobol cotut,tmption,<br />
muijuana tut, being curreatly u,nmarried, aad, ia a U-ahape .d fashion, w&h'oo ccUeQc education °<br />
Koo, Ho, and Ryiasder (24) ezamined a .v'sdc varicty of bchsvion of the non•smotiinF<br />
.+ives of smoking and tDOn•cmoking husbands in Hong Kang 7"hcy ooadudocd thzt in Pnual Vrives<br />
witb hus,bands .+6o bad nevcr amokcd had bcalthier bicatyks thaa w°ivu .ritb axokinj husbands .<br />
Spccifecally, tbc former tvere of higber wdocconomic ttitus, wTrc morc cansdcntious bousc%ives,<br />
ate bcner dicu, and bad higber mdices of family ethzsivsneu as well as bener lealth ut .itus .<br />
A tbird uudy,,by Sidney ct a1 . (15) reparted that dietiry B-r:rotcac iauke was<br />
tipiGcant?y lo+r+er in aon•tmokus eacpcxod to p:ui.t amokc au bame than in non•amokcrs *rbo were<br />
so( czposcd, after adjustmnnt for ag c, sex, ne :c, education rutui, body *eight, and aloohol 'sntakc .<br />
189
They coacluded that dicu.r~ $-ctroteae iatakc was a poccntiil coalounder of the retationship<br />
bc r%=n E7'S ►n d <strong>lung</strong> can cc r .<br />
Ot.bcr potcntiaJ ctrafounders includcd occupation, domestic radon czposurc, a histon of<br />
ezposurc to tbcrapcuuc s rays, and kcepin{ pet birds in the bomc . This tast is raised by a reccn,<br />
study from the Nctberlands wbicb found thit the oddi ratio for lizg canocr among pcople . bo kept<br />
pet birds in their laomc was 6 .7 (95efb conhdcacc intcrval 2-2 20 .0) afier adjtutment for active<br />
amok.ing and vitamin C intakc (16) . This trudy did cot aucss ET5 crposurc amoag the subject s<br />
THE AMERICAN }EkLTH FOUNDATlON STL7U Y<br />
S.inct 148.3, a srudy of ETS and <strong>lung</strong> carscrr in nevcr gmokers has bcca in progress a : The<br />
American Ncaltb Foundstion . All <strong>lung</strong> canctr casc .s intcrvicwe.d in the contcn of a largc, mu] :i<br />
antcr uud7 of tobacco-rclated diicasu wbo rcpon aever haviag s .moked more than out cigarcttc<br />
pcr day for a year are givcn a dr .uiJcd ET'S quutionnairc .<br />
for ucb case, 2 3 bospita:ized controls .rbo have diaf,moses not known to be associa ;cd<br />
vritb toba ;.co use and Who are a.ls.o lifctimc non smokcrs are intervicwe .d Controls t.re matcbcd to<br />
cascs on age (+/- 5 ye .ars), t41. racz, bospitaL, and date of intcrvicw (vrithi .n 3 montlu )<br />
The items in the qucszionnairc include czposurc in utcro ; in cbildbood (spcciTic famiJ~<br />
mcmbcrs wbo cmokcd, years of <strong>exposure</strong> and avcrage number of bours of ezposuse per da}, as : a<br />
subjeaivc rating of the intensity of czposurc), in adultbood at bome (specific family members w1c<br />
smoke(d), nu.mbu o( cpd smokcd by cacli, years of czposure, numbcr of hours per day, subjcctive<br />
raun.g of exposurc, and wibcrc a spouse smoked, vrbet,Scr be or the smoked in the b+..droom), in tbc<br />
+orkplacs (numbcr of hours per %=h., yws of <strong>exposure</strong>, numbtr of amokers wit.hin tcn fect of<br />
r,g <strong>cancer</strong> cascs and 247 matchcd controls. We plan to mntinuc rcaviting subje.as for tbc<br />
study in order to reacb a samplc siz.e of 150 cues. Table
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
yicld approrimatcly I50 maJe and 230 femaJc ncvcr tmokers, bascd oa cstimatss of tbc fre .quency o!<br />
<strong>lung</strong> c.a .nccr amooE nevcr imokcrs (25/,c for malcs asd 105'c fos fcmaJes (7(), 7ablc 7 tbows tbc<br />
sa.mplc aizcs aeczuv} in cacb 1proup (assumiag equa .l tumbcrs of cases and e :ontrols) to detcct RRs<br />
berwcen 125 and 2 .00, witb a ooc•taiicd aJpba of 5% asd 80% power, pvea various proponions of<br />
cxposcd controls .<br />
i4'bilc it is hig.Lly unlikcly tDat tucb a uudy would bc fundcd tolely to assru tbc effects o`<br />
ETS ezposure, tbc ttudy cotild be de44=" to make am imponant coatnbutioa to t,be radon•luag<br />
cunc.cr issuc as .+ell. Spc .dfically, ttud3u of domestic radoa expc>sure luve also tufferc .d from sma!I<br />
ssmpfe iuu and boYC produced .wriablc and uastable ulimatet of tbc tisk of radoa c"sure in<br />
aevtr tmolcrs . la addiuon, tbere is a oecd to better aucu tbe iateractivs cifcru of aexivs tmokinF<br />
and radorr expostue . Sincc ET'S a,nd radon crposure ue bolb risk factors for ltng =ccr, aad si : ;e<br />
one miy, eonfouad, or interaa .rith, tbe otbcr, a large ttudv designed to me .uure botb fauors as<br />
rcliably as possiblc would iuve cnosidcrablc sdcetific mcrit<br />
191
GTS Z SdGZOZ<br />
tabl e 1<br />
E viderrjiotogic Studies<br />
Prospective Studies Relative Risk 95'/. C.l.<br />
Hirayama (1981) 1 .63 1 .25 - 2 .11<br />
Garfinkel (1981) 1 . 18 0 .90 - 1 .54<br />
Case-Control Studies<br />
Trichopoulos, et ai . (1981) 2 .1 1 .18 - 3 .78<br />
Chan & Fung (1982) 0 .75 0 .44 - 1 .30<br />
. .<br />
~<br />
Correa , et al . (1983)<br />
Koo, et at. (1983)<br />
2 . 03<br />
1 .54<br />
0 .83 - 5 .03<br />
0 .90 - 2 .64<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Kabat & Wynder (1984) 0 .79 0 .26 - 2 .43<br />
Wu, et al . (1985) 1 .2 0 .6 - 2 .5<br />
Garfinkel, et al . (1985) 1 .12 0 .74 - 1 .69<br />
Lee, et al . (1985) 1 .03 0 .41 - 2 .47<br />
Akiba, et al . (1986) 1 .48 0 .88 - 2 .50<br />
Datager, et af. (1986) 1 .5 0-8 -- 2-0<br />
Pershagen, et at. (1987) 1 .28 0 .75 - 2 . 16<br />
Lam, et al . (1987) 1 .65 1 .16 - 2-35<br />
Koo, et at. (1987) 1 .55 0 .94 - 3 .08
*<br />
dz-,3TSdGZ0Z<br />
Cell Type Related to Spouse's Smoking<br />
Study "Istologtc Type At' Odds Ratio 95% C. /.<br />
1?atager et at .<br />
(1986)<br />
*<br />
Adenocarcinorna 16 1 .02 4 .33 - 3 .16<br />
$quamous & Small<br />
CCell Ca .<br />
14<br />
*<br />
2 .89 0 .91 - 9 .10<br />
Other 18 1 .31 * 9 .48 - 3 .57<br />
t''ershagett et at .<br />
(1987)<br />
Squamaus or<br />
Smal! Cell Ca .<br />
20 3 .3 1 .1 -1 1 . 4<br />
Other 4 7 0 .8 0.4 - 1 .5<br />
Adenocarctnoma 131 2 .12 1 .32 - 3 .39<br />
Lam gt al .<br />
(1987) Squamous Cell Ca . 27 0 .85 0 .35 - 2 .06<br />
Adj"siL%d for gender, age, and study area .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Srnatt Ceit C a . 8 3 .00 0 .53 --16 .9
3ource : Pron ot al ., 1988<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Tablc 3<br />
Reproducibitity of ETS Exposure Data<br />
Ouestlon Kap a value<br />
Ever lived<br />
with r .gular<br />
smoker?<br />
Ever exposed<br />
to smoke at<br />
work?<br />
No . of resident<br />
smokers?<br />
No . of job sites<br />
reported?<br />
Duratlon of<br />
r .sid .ntial<br />
<strong>exposure</strong>?<br />
194<br />
0 .66<br />
0 . 46<br />
0 .55<br />
0 .37<br />
0 .45<br />
~
zZsTsosZoz<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
"istoiogy o4~ Lung Ca~~~r Amonq Never-SPnokers<br />
IGfales<br />
N ('/.)<br />
Fema/es<br />
N ('/.)<br />
Squamous ~ 5 (13 .5) 10 (18 .9)<br />
Small Cell Ca .<br />
Adenoca . 25 (67 .6) 26 (49 .1)<br />
Large Cell Ca . 5 (13 _ 5) 6 (11 .3)<br />
BAC 1 ( 2 .7) 7 (13 .2)<br />
Other 1 (2 .7) 4 (7.5)<br />
37 53
~<br />
UZSZSQGZOZ<br />
Exposed in<br />
Childhood :<br />
~ Exposed in<br />
Adulthoodat<br />
home :<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
No<br />
Yes<br />
., r<br />
Tahie 5<br />
American Health Foundation Stu~<br />
Cases<br />
i 5<br />
21<br />
Ma/es<br />
Controls OR 957. C .f .<br />
36<br />
69<br />
1 .00<br />
0 . 73 0 . 34 - 1 . 59<br />
No 23 68 1 .00<br />
Yes 13 3 2 1 .20 0 .54 - 2 .68<br />
Exposed at ~<br />
.<br />
Work (ever) :<br />
No 16 4 5 1_ 00 -----<br />
Yes 21 60 0 .98 0 .46 - 2 .10
N<br />
v<br />
Exposed in<br />
Childhood:<br />
tzSTSOGzOz<br />
Exposed in<br />
Adulthoodat<br />
home :<br />
Exposed at<br />
Work (ever) :<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
C `<br />
Tab1e 6<br />
American Health Foundation Studv<br />
Females<br />
Cases Controls OR C .t .<br />
No 17 61 1<br />
.00 Yes 36 77 1.68 0 .86 - 3 .27<br />
No 18 4 5 1 .00<br />
Yes 35 97 0.90 0 .46 - 1 .76<br />
No 17 4 3 1 .00<br />
Yes 27 68 1 .00 0 .49-2 .06
Table 7 .<br />
Power Calcuiation<br />
Odds Ratio Percent Controls Exposad<br />
To Detect<br />
20% 4001. 60'/.<br />
1 .25 1616 1124 1172<br />
1 .50 419 303 329<br />
. . 1 .75 214 161 179<br />
~<br />
2 .00 134 104 119<br />
SZ '-~'TS 0~'i207<br />
aC =<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
.05 (1-taifcd) R - I
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
REFERENCES<br />
1 . hationaJ Rescarch CouncD Emironmcntal <strong>Tobacco</strong> Smokc : Measuring <strong>exposure</strong>s and<br />
as.sessing bcaltb eficcts . NationaJ Auderny Press, Washington, D .C ., 1986 .<br />
2 . Dalagcr NA, Picklc LW, Mason TJ, Corrca P, Fontbam E, Stembagcn A, Bufilcr PA,<br />
Z.icpJcr RG, Fraumeai JT . The rclation of passive smoking to luni unccr, Camctr Res<br />
46 ; 48084811, 1986,<br />
3. Pcrsbagen G, Hrubcc Z, Svcnsson C . Pauive tmokin.g in Swcdisb women . Am J<br />
Fpidcmiol 125 :17-24, 1957 .<br />
a . Lam TH, Kung 1TM, Wong CM, Lasa WY, Klcevcas M'L, Saw D, Hsu C, Seneviratne 5,<br />
Lam SY, Lo KK, Chin WC . Smoking . passive smoking and butologacal types of <strong>lung</strong><br />
ca,nccr in Hong Kong Chi .ncsc womcn . Er J Canccr 56 : 673-678, 1987 .<br />
S. Hirayama T . Non-smoking wives of bcavy ssnokcrs havc a bigber risk of iung caacer : A<br />
study from lapan . Er Med J 282 :183•185, 1981 .<br />
6. Tricbopoulos D, Ka .land3di A, Sparros L . Luz,g cinccr and passive smoking• conclusion of<br />
Grcck stud~ . Lanctt 2. 677-678, 1983 .<br />
7. K.bau GC, Wyndcr EL . Lung canccr in non-Smokcrs . Canccr 53 : 121~-1321, 198: .<br />
B. Garfmkcl L, Auerbacb 0, Joubcrt L . Involunta.ry tmolcing and <strong>lung</strong> canccr : A casc•<br />
control study . 3 Natl Canccr Inst 75 : 463-469, 1985 .<br />
9. Lee PN . Passive smoking and <strong>lung</strong> <strong>cancer</strong> association : A result of bias? Human Tocicol<br />
6 : 517-524, 1987 .<br />
10. Lee PN . Misclassification of Smoking Habits and Passive Smokinb : A revicw of tbe<br />
cvidencc . Springer Vcrtag, Bertir„ 1988,<br />
11 . F}ciss J . Statistiul Metbods for Rates and Proportions. Wiley and Soas, Ne•. York, 19S1 .<br />
12. Pron GE, Burcb JD, Howc GR, Miller AB . Tbe reliabiliry of passivc smoking 2ustorics<br />
rcportcd in a casr-control study of <strong>lung</strong> ci .ncer . AM 3 Epidemiol 127 : 267-273, 1968<br />
13. Fricdman GD, Petiti DB, Bawol RD . Prcvalence aad correlates of pussive zmoicing . Am<br />
J Pub] Hcaltb 73 : 401-405, 1983 .<br />
14 . Koo LC, Ho J H-C, Rylandcr R . Litc-history wrreLtcs of environmental tobacca Mokc :<br />
A study on non-smolcing Hong Kong Chincu wAvu aritb tmokisu versus oon-smokiag<br />
busbands . Soc Sa Mcd 2b : TS1-760, 1988 .<br />
15. Sidney S, Caan B3, Friedman GD . Dictary intake of carotene in noa-tmokers rvitb and<br />
witbout pauivL tmokiq at bome . Am ) Epidemiol 129 : 1305-1309, 1989 .<br />
16. Holst PA, Krombout D, Brand R . For debate : Pct birds as an indcpcndcnt risk factor for<br />
<strong>lung</strong> canctr . Br Mnd J 197 : 1319•1321, 198b .<br />
199
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
7
Kalandidi, A ., Katsouyanni, K ., Voropoulou, N ., Bastas, G .,<br />
Saracci, R . and Trichopoulos, D ., "Passive Smoking and Diet in the<br />
Etiology of Lung Cancer Among Non-Smokers," Cancer Causes and<br />
Control 1 : 15-21, 1990 .<br />
One of the European case-control studies to assess<br />
workplace <strong>exposure</strong> was conducted on hospitalized women in Athens,<br />
Greece . Based on 89 cases and 118 controls, the authors conclude :<br />
"The effect of <strong>exposure</strong> to passive smoking at work was very small<br />
and not statistically significant (the RR between extreme quartiles<br />
was 1 .08 (0 .24-4 .87)) ."<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
Cr.•C+ ...,-xC .y~. 1 . 15-S1<br />
Passive smoking and diet in the etiology<br />
of <strong>lung</strong> <strong>cancer</strong> among non-smokers<br />
Aana Kalsndidi, FGcl F.2tzanr=ni, Ivelly Voropoulou, Gwqc Bastu .<br />
RndDlfo Sa=a . aad 1}imiaios ?ricbopoulos<br />
(Received d 1! pri; 1990 : rec :ccd m revited jarm 1 M.7y 1990; :c:epted 3 Ala7 19901'<br />
A ore-mauel rscy .v eanu=ksa ia Atam m apiors ctc toi. °d psvs ~niin ; :nd dic in thc ouasrina of iun= c:acc:, by hiudoTic<br />
rype . in s~o•ema~aF .omm . Alaeej 160 .romm .n1L luaj tanc• adare¢ed co oat oi ie+ .a majot haaicl, ia Gmaca ,+.mrm e.n..r 017,<br />
aad 1919 . 1N wre mirs.~od ia lxaor. ; d oese iaterie~et' . 91 .ers lu~ .ioe ; .na .=o4en lateat 1G0 iosaxuied qeuait rita xtturet<br />
er a~hs .r erslleprdic mndianaL 145 .cr iecrn .+vd in srrrat oE uwt∎ iarrms+.d . 120 ..ers liie .losr oon•®oicm . XiCSie_ii FCV_-smr.titlu- .r<br />
; . .+man o a ooi.r ru -a-iar.d .icA a MIXa.a aAY bur laaj aaea o[ 2-1 r1S kC*QrKL==ixue,al I Q I L 1- (11 ; anmDa oi dprsua imulszd_<br />
l dsilt b1 mr ka .lund md rc= nf acaorum w kmmL.d', +unnicia$ src pcusi.WiT . bnc .« :rsifias dr; i=W=d oa iaaT-a .ori* aa~" T~uc aa.<br />
.o erit>ras oi anT au.xiauun .+tn e,zfns to asxaoan= Cd utbu bouxheid acaibca . ud the rmladaa .itb eLPIwess M Ftuus rsakic ;<br />
ac +rork ..A amall aad ao( lna .dnll,r a=nifiaae. Dieary daa mlleesrd mrnure : a~i~mncia>i•c (ood•fiw{umey qoaaoeaairi iasirarnd<br />
tbx 6ifn mmuapuoa ai uuie r~c in .eas.FT rsiued m tAe aJc ef 4ur onsa (cbw reoare mc benem a : :+tm .e qaaruLr .ru 0 .11 (Q 0 .10-0 .74)) .<br />
Neitha .efcaL.ir oor m . ovr fo«1 rcoup C~d - adLicieu,t ptoec :".. d'ic-¢ : iurti~ ds aF- p :vc.ca .e irect oi ~qsta6l~ -<br />
ao[ dnc to aocmoid .itmia A coatcat sad - ooi7 pnn77 apimcd in tc~ of iamin C . SS~ aooci.aao
A. ICA[aa"w± r. 21 .<br />
with a dG airc dia .gaosis of <strong>lung</strong> caaccr fonaed the ase<br />
ut~ie:• Tbe basuirals induded all rhrcx nacgr hospias<br />
s`a t{ris ua- mc oaly hospi=l for chttz diseasa in Anc=,<br />
aad %~e tarr_ largesr uaivetxity gsocal bospictls . Womea<br />
wmr iacludcd .rhm chesr .rss a posxcive bismlogic or<br />
,CqmlogY mmiz2zin ., or wa= 6rvocboscopy was caa•<br />
sdrred dia ;ncuCC of pr:maiy bromho6=ic nrcaorna.<br />
A torsl of 160 cua .czc idr^^ rd . Concrols wns 160<br />
.romca hospitalized in the ortaopedic dcgucmcac of<br />
the suxc bospials or the oe=zby bospiul for ortacpcdic<br />
disorders, w .obich mosi ac :idcnr esa from Greatc<br />
Atars and Lne sur:ouadiag .ren. ate ad.=iaed . Cont.rols<br />
wce rindomly u?ezud froa : thosc acimiracl virtia 3<br />
weei -- ;,: tac aa of a corztspaading cue uid<br />
bad to be 35 ycza of agc or ovc . Araong ncc concol<br />
.rors~, 10 : bad &ctura and chc rc-Aizing 58 had<br />
ots,cr ;riumacc or orrnopcdir condiriar-f .<br />
A1! esa a.nd coat:ols vcr inruviewc` in pe=n in<br />
tac hospiral wards, ss soon as a dcEnice diagnosis Mu<br />
by one of ffvc intc :viesvcs who nch intta•<br />
rie.rcd tae ssr~c proporcioa of ases an d cnntrols . Therc<br />
Wrse no rerur+ls azaong eascs but siz werc too ill cd be<br />
inrcvie++rd. Azaoag wnaals, 1L xc: in n eoadi:dn raar<br />
did nor pe.-=ir iacL-view, aad chrr_ rcused ca ourc ;d•<br />
pa :e . !n the iace:vie•as, paucsa .+csz sskcd to iacicuc<br />
in det:i? chcs lifelong smokiog iusrocia . their =osun<br />
m psssivc sraokir:g--aom thcu hwbac .cs, E.roc ot'tu .:<br />
house:zold membGS aad ar work'-as weil as a au~e<br />
of other d=ognphic . soeioezonosaic, and medial<br />
c:=rr-isda . Subjcc^s xcc also asked to estimau the<br />
avca,-c arquency oi mnsumosion (per moam, pcr wc--zr or pe<br />
: day), befort the onser of the presenc diseasc' of<br />
47 food iusns or be-resatr areTorie7, These itr.ns wcs<br />
srle.'ccd irom ar1 e>zcrosivc lisr of 120 irems . using the<br />
aii=oa rhas ttu aderred isr= should cover, collexvely,<br />
more :han 90 % of ti7e ia .rsltie of ent:h of the eaagyrnc•<br />
acag autriena as pel .l u of vinra.ia A. This citcricn•n.t<br />
rsz+blished oa iafnrmsrion firom coacrol rroups ia a<br />
nurabcr of ase-conaol srudies uDde :dcra ia Athens to<br />
rsplorc the rolm of diet in tbe aussttion of ance: u<br />
.Kriau sfrcn .t1<br />
Lzfatirac espoasse to air palludoa was maualled ia<br />
the analysss aa t3u basis of iafor~na aboar thc lifelnar<br />
rmidmial aad cnptoPmezzc addrrsa of all subjeszs . The<br />
art:as of residtace aad work we=e divided inm fire<br />
earrYoria acsv,rding to thair esumattd ourdeoc a'u-pollu .<br />
tion lrve4s . Fnr tize Greazcx At3xas uea, air•pollutioa<br />
tevals by bomugh wKZe akulased on the truis of rhe<br />
mcaa yea.dy m.cuu.rzmeaa (1983-tS) of smoke and<br />
NO ;, as record.ed ia 14 monisnria ; staricm dirpcrsed<br />
tlsrouihout the atea . A Linc for zcro i .ir pollucioa wzs<br />
dnv^n ar the highesc powa of the turrounding mounuias.<br />
Por eazh borou.gh, the alsuhud air-pollution Icycl<br />
w'3s t.~tt avt."7.t'C Of ttf .e n]eaAlrerAeats of the three nCZrc3t<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
16<br />
:utioru . or the two nrurest and r,be tcro air•polluaon<br />
line, vcigbred by the inre:se of the disu : cc f:ora the<br />
borough's c=tr : to rhe mcasu.rtzmenr points . Boroujhs<br />
wcrc thcn dividcd iazo four cucgoria, amgory < being<br />
the morr polluted with dai:ly smoke rnlues fsequatir in<br />
esr~s of 400 µg/ra5 and acerory 1 br:nc the les<br />
polluced Yrith das7y pak-sxnokt ralua rusly escr.diAg<br />
100 µ¢/ms . Pan rcadentes in rural ar semi-urbaa arrss<br />
(populsrioa less t3n.a 10 .000) Mcre coaside:ed u<br />
a.rrgory 0, mbems past tssidences in other cides of<br />
Grcce war clissified in nuyories 1 or : according to<br />
the tccordcd or pttsi :med 1erds of zir pollur:on. F'ua::11y,<br />
fnr e9e .-y individuat, a time•wcig:crd st: ..~ :was e: :J1:ud<br />
avu=g 40 houa pr. wc-s worx :ag ri .:. : fr : individu_1s<br />
worSr:ag ourside the home . For housewivcs, their bocae<br />
rtsidcacc fo=cd chc oniy 6^sis for estizaa : :ng thcir airpolludon<br />
crrosure . Wbcn 211 si:bjcas had zwei; airpoiution<br />
cposius assexsed, rkry werr disciburcd iatz<br />
fou: r•roups based on ttc masgin_1 auuriles of trc air<br />
polluuon i : dcz dismibuuoa . Since it is possiblc rhu tae<br />
hospirl ! crc.7mcar ucas are l:rger for ance: paxients<br />
tnn.r: for paz:cats with minor f:artures and rmumu, the<br />
possible ait-poUutioa artocia~ns wce o .kci ins aceount<br />
oaly ia or~cr co eonzzol for possibie con .faunding<br />
(gccm .zed 'e .' eicnG tcauiae cusal eae,.= or rhmugh<br />
selecaon forc=s), and noc for asscsrzaeat of cuscliry .<br />
Amons tr : 154 asea, 91 hsd be= life-lont noasmo<br />
:rs (las ;han 100 ei=sresr3 in thcs a .aoag<br />
the:a, 4-4 were diagno3ed bisroloTically (38%), 34<br />
c?rologicu.ly (3846), and 13 (14%) rtuough bronchoscopy<br />
. Among the 145 conaols, 120 had bern liie•lon ;<br />
non•mokea . 7he analyus was cnc;~.ne3 to li:c•loa= notnsmok=<br />
.<br />
Thrce souxe of passi®e smoicing -mined in the<br />
prro= siudy we_•r : busbzmd's swakiag ; smoiiag of orhe+<br />
household racmberr, aad crpostut ro smol;ing u worY .<br />
Ezposurr to husband's smohdng was conai~e.rorl co surr<br />
u the timc of marriag•c or when the husband statsrd<br />
smoking (whithever casnc secoad) asid to end when the<br />
busband stopped smokint or dled, or the couple<br />
sepas7ced (*hi.tileres ame Cissz) . Chaa .ge of husband vu<br />
considcrd equivalcsrt ta chante in tuubaad's smoki .ng<br />
habits, whescas sin ;le Wamen wcs eonride:ed aa<br />
v.acmgosrd to husband's tmokiag . Ye= of esposure m<br />
busband's smobinQ and av=ge numbc of dg•uertes<br />
smokcd daily by the busbaad wese scpantcly carained<br />
in t3u ana.l7sis.,<br />
lsposurc to the smokiag of housebold mesabers oc}sc<br />
rha.n the heuband .ns assosscd by taulrtplyinr rhe yrsr :<br />
a worrsan livrd in eticI af brr bnmes thtouthout he : life .<br />
with the aumbe: of smo4cn in ehe correspondin ; homc<br />
(esauding a+se busba .nd) and by summiaF thcse produr .<br />
taZns . 5ubscqueady, all .romen we.ro disttibutcd inu<br />
four groups; one connining those who lud never bee :
Lrxl caucrsmaxj sow•rn .airrr<br />
1 c'Po'cd co ps .ssive smoking frora mcmbca af 6cr<br />
houscaold ; aad chree corrsponding to the rerriles of<br />
ino riucr bouschold espoaue . Finally . csposure co<br />
pusive smokiag in the wockplar_ rzs cilculurd as the<br />
cime•wcigfircd stua af expcsure co smc!!c in rca-ycor groucs), years<br />
of scinooiiag (quzndcuivcly), arld inu :vie•ar• (four<br />
I P nkug 6W LAra V=,d<br />
iacucazor varab(e : ) . Ad coaEdcnce inre: ras silov+II ue T,tk 2 pomb=m d 91 acc-i-ahaf .aac .-,c <strong>lung</strong> esscr aad<br />
95!'c irscemis . Analyses we-'e donc using the GLLM 1~ma~cl~ramp.rioon .ummin+e~dp~rarMresolss~wurc<br />
sruucal pzc>:a ;c (Numedral Algoruilru Groun lnc., ro i=K tA1O'iet (a-sQ a "d-)<br />
Rticse 3 . 197y) .<br />
Results<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Tab1c I shows cbe d'u ;ribucion of caaa and cooaob by<br />
selecteo-d dcmoYzphic chu~ia . Thcre ur ao<br />
sigaifirar differe=es Mich rrspccc to W . 7ea.u of<br />
tdzooling, cuneac ruideace aad =puion, crra chaugh<br />
ctsce nrisbles were concoUed for in subsequenc mula•<br />
ruiarc ualyses . Table 2sho .rs rhc disaibudon of om<br />
tnd coaaolt by sclecicd paramccea of cpnwrc m pass .i+~<br />
okin 'jXer'r }i' c.idcact dut<br />
:i un~moki~ 6 auociatcd .'rch >aaasc~ti~ ."d oo but the<br />
diffsrcnces ox aoc 1srp essou{h to be iarerprenble<br />
.'ir.iroui concrollint for confourlding e»fcc=s . TaBle<br />
compara ctu diso:ibudon of cues sod conuols by llfdaoi<br />
aposum to rwcdoor air pollucion . Zbc two di>zxibunoox<br />
us slaaosc idencinl . Finnlly, in Tablc 4 the discriburioc<br />
olases znd conccls by btqucncy of coasumpcioa of<br />
spcrificd fnnrI xroups u,d nucicnc is pnwrnsed .'Ihe•re<br />
cs no clut .,r sutzexcive di$ucace ber.rorn cises aad<br />
conuoh mich rapccr to any of che indicaccd aurriticaiI<br />
ruisbla . ezccpc for cercais (P - 0 .04) sad fruin (P •<br />
0 .11) . Thc u.aciatian vich cercals is posievc but is aor<br />
biotogically , rcdiblc . is noc suppotud in the Ucmauc,<br />
Qw~ CLM c"Mis P<br />
Hwh .nd't aadca~<br />
Ci~et~s~dsy<br />
~cra crmkcd 2{ (23 .9) ~6 /39 .7)<br />
:- :D y4 (31 .t) !9 (li,d) 0.16<br />
21-~0 21 (24 .1) 21 (t9 .0)<br />
17 .a)<br />
H' " c'oiOt'"=<br />
D"°L0t11 Gq'O"14<br />
k Xd-,w&U R 31 .<br />
73bk 3 . 0issbuaon of 9 i om•enarin( wacnre rrm lunl anccr and<br />
1:0 aon•wnotu= malparuan .vmca by iada oi )ifclnaF eziaacut<br />
ee .wdoar air peiluccn (V«a;u In pr+=4i--%=)<br />
Mr poUutioo indeY Caa CO .+aolt<br />
1u quaKilc: .etT b~ 32 ()5•2) .L3 (35 l)<br />
2nd q,arule. 10+ 20 (22 .0) 26 (21 .7)<br />
3rd quattilc: mcdrnu 11 (19 .!) 22 (11 .3)<br />
4rb quunlr- b.ija 21 (23,1) 29 (21, :)<br />
f (or (+aar accd - 0 .99 .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Tabk 4• D'a(nbunoa of 9l con•mokir.t .omea w cn luc~ aaca .ad<br />
1a0 Ocn•anoc:a)( corn¢uaon .aaxn bv ipprmr.u: r.ar~ oa qurtSn<br />
0r a c! trcqucry uf xnn :macon of s~r. i c1 Eooa rtou p u d<br />
aumr_a (parrr.njo in pursmcu :)<br />
i,,kAe c =Liawd<br />
Food puup (Zuuri)a 1 ~:r<br />
.r wu.ear t(~l 2 3 4 (~ln) liresr<br />
cest<br />
l,c-~mi (prriotmed)<br />
u,n 22 (2~ . :)<br />
maacfr 3U (25 .0)<br />
p ., ucoe<br />
a~o aS ( :'• .5)<br />
coaau~ 26 (23 .i)<br />
E004 rta: ;r Qulr, :kn P fot Ytamw C<br />
0r ouuit-V<br />
1 (Lzw) 2 3 SfH~ni<br />
(usrst r LW 30 (3~,0)<br />
~ ;qnrrais .S : (tl,s)<br />
cscs 2' C19 . .'7 16 (17 .6) 34 (37 4) 14 (15 .4)<br />
tm=/s :i (35 .1) 3a (21 .3) 33 (27 .5) 10 (1 .3) O .Oa<br />
Os6c eao-umsolk Me.c~<br />
acs 4d (4t .4) 30 (33 .0) 17 (11 .7)<br />
~ 69 (57 .5) 26 (21 .7) 25 (20 .3)<br />
V==n A<br />
ase 23 (21 .3) 21 (23 .1) 20 (22 .0) 2' (29 .7)<br />
maaau 30 (25 .0) 31 (16 .7) 32 (23 .7) 26 (21 .7)<br />
Tod rmerLry<br />
ca .v -' 3 (Z1 .3)<br />
convr.b 30 (25 .0)<br />
13 GS i) 231( :3 .1) ` : (27 .5)<br />
3P (15,0) 32 ( :6 . :) 21 (23 .3)<br />
.<br />
~oawa<br />
e-:n<br />
oorurou<br />
7 (7 .')<br />
14 (11 .7)<br />
)1 (19,3)<br />
27 (2'.,5)<br />
53 O1, :)<br />
5; (47,5)<br />
)3 (1 : 3)<br />
22 (11,3) 0 .37 is not p;rucularly r auai . u;d may veU bc<br />
by th e atlltiplit:iry of comparisons =aac : it sns n~<br />
SuOsn<br />
fursiler ezploced. By<br />
corsnst, cbc ncguivc a0or'sti=<br />
q:cs 2Y (30 .3) 24 (:6 .4) 26 (].t .6' 13 (14 .3) with corlsumprioa o f %wi(s is bioiorically credibic liren<br />
cmuou .4 (36 .`) 30 (25 .0) 31 (:53) 15 (12,5) 0 .40 cbeu high coc=l of vitamin C snd some atrotr..t4rs is n0 d!5er= risl diezuy reporting br.xees a¢s<br />
V<br />
ca&a<br />
osauol+<br />
27 (29 .7)<br />
34 (2t•3)<br />
12 (24 .2)<br />
36 (30 .0)<br />
11 (19 .1)<br />
29 (24 .2)<br />
24 (26 .4)<br />
21 (17 .5) 0 .14<br />
tnd CODII'nli .<br />
The anocizxioa of<br />
<strong>lung</strong> cmcez wit5 ezpcrsum oo pusiw<br />
sawkia; through marrA(c la s>9sOking husbandr .u<br />
huia<br />
Euruler cramiaed by mukiple loQircc tsTrasioa,<br />
ooa<br />
sona.u<br />
37 (3t .5)<br />
:2 (11 .3)<br />
19 (20 .9)<br />
44 (36 .7)<br />
15 (16 .7)<br />
24 (20 .0)<br />
23 (24•2)<br />
30 (23 .0) 0•1(<br />
~ coaaolliaZ ~ for aje. )esn of ~, .Soolimj, lnd iarexiew-~ .<br />
~pc-maIIte Ctk ( U) COn3A7S1nx t.ntt= Miilitrl< 1G<br />
Haa. 5cti . .W<br />
a.a 26 (2t.i)<br />
toauaL 39 (32•5)<br />
23 (25 .3)<br />
27 (22 .5)<br />
21 (23 .1)<br />
31 (2S .i)<br />
21 (23 .1)<br />
23 (19 .2)<br />
i¢w}x.a .rixh 6" msaitd to non•smakra mu 1 .92 .'stf2<br />
Q 1.01- 3 .59. ' Th e CL:rea of slle avcrap out5bcr af<br />
0.57 djusrrrs m:aked daiJ7<br />
by the husband uld rhr dun>=aa<br />
1(IIk tod auLk pmduco<br />
a+a 21 (23 .1)<br />
cenuoL V (22 .5)<br />
29 (31 .9)<br />
32 (26 .7)<br />
14 (17 .i)<br />
30 (25 .0)<br />
21 (27,3)<br />
31 (25•1)<br />
of marria;e to smokens<br />
*crc evalulced in nro diirerrrr<br />
alodels, eoarrol.lin ; for the xme coce .asisbles ss :ba-<br />
0 .74 snd inuoducis2t, slrcraaci.elp,<br />
the daily numl+c: of t'~<br />
drurnes anc3 rhc d untiaa of marziage u qusatincTe ~<br />
Fan utd als<br />
tcmss inten.ui.nj with<br />
the smoking mrus of the husbxesi ~<br />
ICUa<br />
mavnl.<br />
31 (27 .5)<br />
37 (29 .21<br />
2d (2~ .4)<br />
30 (21 .0)<br />
33 (lb .i)<br />
33 (27 .5)<br />
9(!•!)<br />
22 (11 .3) O ."<br />
(the 'rau' device) .l'-<br />
u Thc <strong>lung</strong> anca dsk amoag oow•tin<br />
irnokea inaesse d by<br />
16% fnc cYerf 10 )reaa ef el¢owir Q<br />
Ceh<br />
a.a 70 (76 .9) 10 (11 .0) 11 (12 .1)<br />
to 6usbaad'1 msoking<br />
ssd by 6X for r.eiy sdaic"fjj<br />
' padc of cipascs smokcd<br />
duli . Thae alinuces sre lo+~„~<br />
tunrroh 95 (79 .2) 1s (13 .3) ! (7 .3) 0 .44 and sruistially noo- sitnif'lslnr - pcobably bcrause . WUrCA<br />
tu<br />
C.3<br />
~<br />
0 .u<br />
0. :<br />
0 ( :29) 20 (aa,0) 27 (a4,7)<br />
55 (:' .5) 33 (2' .3) 2L i : : .') 0 .61<br />
16 (1 ; .6) a3 (as .i) r. (2 .~1<br />
3!( (31,7) 29 (24 .2) 31 (22•!) 0 .30<br />
=5 (S7 .)) !t (19 .!) 21 (JT.S)<br />
27 35 (27,2) 23 (23 .3) 0.93
52<br />
4!<br />
7 .1<br />
!,r<br />
.) :<br />
7M<br />
Ile<br />
1.u+t tsncer tr.onY aon•taolcrr<br />
Chc smoiuag sucus of dsc husbarld is rz:.idly asccrmiacd, lUU :llL<br />
.•i• 4J 14Uw iT1C111111gLW ' "'1CLLl UC Lil6Ci"uYC<br />
th e q,,,nhauve aspeuts Of thc esposure ue difficulr to el.iezis, if aay .<br />
The last mode ; vu also applied separuGy for adeoo-<br />
j~ey y,Ce'1Sr'aCely,<br />
5imitu modea ~r .r used to ssscss the e6ccn Of curinomu, an one hand, usd For squsasoL=, srnail• usd<br />
ctparutc to cobacm >znoking by ochos household mem- luqe-cdl raninomas, on tiae other, using in both inbcrs<br />
ot at the vorkphce . Tbc rmulc t.ere qualira>? .cly rcuces the total sez of conuols . The raults are sbown<br />
~rilir to those pcesrnteA in Table 2 . Ihere ru no in Tablc 6 . !c anpnn that the cEcra of inuivr smokin ;<br />
tvidr~cc of any e. .~ from cxposvre tp smohinj of or}sc ue more evident for squarnous sraaJ.l- and la:gc-c . :1 cu-<br />
bouschold mcrs'ea• •hems the ettect of aposure to a .^•omas tahca tojr., :er . tha•n for adGOCUCi.oomi,<br />
passive sasokinQ u•osk was .crq szas!J and not stzrist- altt ougb c!s diac :=ce is eot sazs-icslly sirftii:rrm. On<br />
ically siguifictt (the RR btc .re= eza=c quartila .ru tsse contruy• the nutr'uotvtl facarts) assoazted with &%tic<br />
1 .08 (0 .r4 -i .87)) . CnaanUing for ur poUurion had no constunptioa appru m be equally strnng in boc~" gups .<br />
crr.r on any of the mulciva.^ate anal,vses .<br />
Ta .blc j sho" trultiple logisriz tzgre9,ion•deaved RR Discussion<br />
for <strong>lung</strong> c-.ace: =or.g non•srnorea bc :wrc : ersemc<br />
quar-~es of sc!ec :ed food gcoups and autr.ents, Tne r2R Thre: major :r.>orz yave cooduded cttu c:e ::ist :nj dan<br />
estimatcs are adjusced for agc, ycn of scbeoling, strongiy support a causal relat :on be:-cen pustve<br />
intc :viewe :, zLd total energy in : ke . There is licle, if snorci.ns ind <strong>lung</strong> ar:cer ."' ~a Ihe : have been zl .io<br />
any . coaiouncinC 5c .-Wce: the two indicated food groups more man 10 epIde :%ioiogic szudies uscui ;y c:.c role of<br />
(ve ;eubiez u:d i.•uia) or among d-e thrr. indicrcd nutr•.tion in the r.iology Of <strong>lung</strong> ca:.c :: . In a enttca)<br />
nuu-ien :s . Tr,c :Cbre, the dau su3ger, citu fr.t :a, bu: noc revie-x, WiUer. .7 sti:rrrsaazcd the NICC:cc s bcing<br />
vcgenblc, prot :: ag2inst <strong>lung</strong> aric : :, as:d that vitimin te :aarxably corsisrce in sL:qresdnY sn invnac association<br />
C alone as,not e=laie all or taosz of the protc-cive c5ect be .-w= arorenoid ioureea of vi :nmin A and u;e risk of .<br />
assocacec wicn fr.:ic corsumpcon . The--e s ako evide nec ' t!~e discsc . Since botn espon:rn to passiNz smok:ag, and<br />
that rerrsol (prc-fomud vinm .in A), "ru from beinp a dir, pc>or ir fruit and veVta ..bles, mz'rr?e: inade_uuc<br />
protective, miy u:.a11,v be usociated with 1a int :eased heaha edua ::on, it is conncivablc Ihat e:ca of tite two<br />
risic Sor lur•,Q m:ces in this se : es. faceors could coaiour.d the te:adoa of che other to the<br />
Fia.aly, eposur: to husband's tobacco smoic :r:g, zad rislc of <strong>lung</strong> aace : . Tae preseat sasdy suptcre rh= tbiz~<br />
fruic coor :rz:pdon were ss:usuluneously introduted in --I is aor the asc : the-ef&='of pattive smoYint attd die :<br />
anotiur model (toeethe: with ige . rrus of schooiing, r sppar to be itsdc^.,esd=trkt:sdual coaioundi .lg on cae<br />
inte.-vicwc :, and tocal cn e :gy inta.icc) to csplorc vhe-.he: basis of a conceivable as:ociation be^art-cn hr.tsbznd's<br />
the p-_ssive smoicing cicct is confounded by inadequate smokinf of hijh tar (ntae : than loa nr) aptertn and<br />
insa-kr of fruia, u ;d vice vea.a, TAUe is no suca evideace, icadeeuau fruit inmi : by his wife is unlikel,v, bet7 ::se<br />
In fact . we RR ~-i~ted .vith enposurm tn husband's hirh- and low•tar ctar-es coafe : simiiar saostses in<br />
tobacco sraoking inueased from 1 .92 to 2 .11 snd the the eoncext of pusive smokinQ (ru intaice dep=ds<br />
relItive tisk usodatd .rit'rs high u, low coostuspdon of ptir•arily on the filte : uscd) . Furthe . .^•,ore . the special<br />
huits deerascd frnm 0 . 33 m 0 .2' . lnaoductioa of eceals c-or, to escludc cx•smokcs hom the study of <strong>lung</strong> ances<br />
to the laft mui.el had ao effecs .iiereas the study was amony aon•strsokers pteridea ururaacc tfiat the surln<br />
Tab4 S, 4ulcpie lofnoe aTresiorrdrmcd reSare riyk fw istn{ noea<br />
unonj Ooa•emoiee benem aaeaie yunnilen .f rlecuc ~ud ~toups<br />
K LlC.tieltp<br />
tood jroup or<br />
liiacis rndc Coatidarct P nlw<br />
.""nt<br />
bKr.ees essrezae roanl•<br />
---~ ., .<br />
rl-c.ure"<br />
qv&ml-c'<br />
l .ot o.u_ l .sa 0.96<br />
lssimt(prr{artwdl<br />
Vux=a C o .s~ o.a- t .os<br />
0.06<br />
o.ot<br />
v.Yeflbin 1 .09 0 44- :,0! 014<br />
frwn 0 .11 o .ts-o .ia o.tt1<br />
'CancroUMf tnr a~c . .na nlunayint, iorw~s+.er, sr.d wa cecrTy<br />
Meyk~,<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Tzb1 . C Mutripk laruac w~emms.iev.ed adad.e tW (9)X<br />
eoandeece ia~) >bc Iu:C aocr, by b .M)otic s" anwnI ron•<br />
smuicr, urorriinl to 13ssbiod's eoCaao rmok .os runu U~d so lu(o<br />
n . bW tuartik oi fruie eseuumpuan,<br />
HsTaotial qpc~ Hubwi uaakr,<br />
a. ao"awJms<br />
All kaag aocsr<br />
nde,aocuabeta„<br />
Syvsmar, sm.l1• r •<br />
kuir-cr0<br />
2-11 (1 .OV-4 .ap<br />
:.SJ (O.Yt-7.)7)<br />
Fn:io cusumpuac<br />
h46 er . Sar qwrcle<br />
o . :1 (o .1A - 0 . 7 4)<br />
O .1a (0 .0 4<br />
{uettallieR fat agc . re•us Of s&Ml;nK, mur.iesr. usd roaw cncrp<br />
Ltetk i .<br />
4of :i of tfu it eua 6i,+olo" rope vaI na i .n,ublc .<br />
19
nsivc ~<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
aaoSci.oj znd histolo8ial rypa in lunj ancee it HoaB<br />
Kon( Chincx wcxnen . Br f Gsur 1917 ; S6 : 673 - i .<br />
6. }:oa LC. Hc JH-c . Saw D, Ho CGF. M-1- aa oi psarrc<br />
smckia{ u:d estimua of lunf mca risic uaortt aoatmokio<br />
j Chinc-3c feasla . !sr f C,usus 1917 ; 39 : 162 - 9 .<br />
7 . Gw Yr . flloc WJ . Z'hmg m . is al. Lunj eaaca ataoa{<br />
Chincx vor2crt. l.f J Ga+sn 1997 ; 40- 604 - 9 .<br />
1 Inouc 1. Hiuysma T . Pos;ve saoLiaj snd tun8 cacica<br />
in wmea• 1a : Aoki N, Hiuraicai S, Tomi .up S, cis .<br />
Smo,Fbs od Nealcb 1987, Atasscrdua : lssc^cc n~cdin<br />
19ye : 2J3-3 .<br />
9 . Cxn GY . L'ung 2H . 2hsa5 AY . Wu GL Oa cu rchronrhip<br />
bc:.rr.c smokin j snd fc :nale lunr atcct . ln : Aoki<br />
U . Huamiciti S . Tornicuyz`S, eds . Srco.Ersj d Hcr[tb<br />
1987, Amstr.e:r : Es:e:pc: ](edia . 1988 . 483 - 6,<br />
10 . Shimizu H . Koruhin M, !lirano K, st d . A au caauol<br />
r.udy of <strong>lung</strong> cuscc: in non-ralokin j wroca Tonoex J<br />
Exp Mid 19Ytl : 154 : 389- 97 .<br />
l l . f:aeauyznni K . a'illetr W, Txichopoulor D it sL R .i•tk of<br />
breu: anr. : zmoo( Grce3 vo©cn in ts'stion w nucnent<br />
incake . Gr.ur 1961 ; 61 : 181 - 5 .<br />
tz . 1Lcmncn OS Ti.orzncal~rJ.~17 . Nev Yoric : Wilry<br />
blcdical• 085 : I16 - 44 .<br />
13 . Tcc.':epoulos D, HsicS,C .,1( :cJtahoa 15, it sL A.ec u say<br />
'sittth snd b cn :a csncc: risk . tsr J Craars 1913 ; 331 ; 701- i .<br />
14 . Nuiorul Resratc5 Council, Commicccc on Pcui.e<br />
Srnokia j . Errvorrn.n+Aa! Tovu:.ca Ssrole : Mrarurrrt .<br />
• Erparu .rt o+d .iuis.rs„j Hralib E',ficrr . IS/aabinr :oc LK•<br />
Nuional Anduac Ptcsr• 1986 .<br />
15 . Sur ;cnn Gcnr.tl, Tqe Nakb Conuwi :.crf of Irx.Gr .ca7<br />
Smeiicy : : Ri.eon . llock~iLe• Msrylind : US Depus.:.rst<br />
of ticzlcb add Human Scr .ica, P•ublic Hcai ;.5 5s :vicc,<br />
C= :ea for Disrue Control . Cratc : for HcaJch Pzor.ucien<br />
snd Uuta :ion . OtScc on SmoEinj tnd Hci1tL• 1915 ;<br />
DHY-5 (CDCi 17 .i398 : 332 .<br />
16 . Wodd Hcaith Otqusizz:ion, Tobaao SmoEr'sj, LA•3C<br />
Monoftsphr on t6c EYaluuioa of the Camino jeau Aizk<br />
of Chcmrala to Hur.zas : Vol . 58 . Lyoa, Fnncc : 07orld<br />
Hcslth Orizntsacon, LkRC, 1986 .<br />
17 . C!lillect W . `'uuirionalEpialtnr.eku, New Yotk: Ozford<br />
Uaivearry Press, 1990 : 292 - 310 .<br />
111• Sut;con Genetal . Tbe Hrslrb Cox.utsnccsr ofS.o.4-ri.j<br />
Lnr j cnaen tncon j :o .-twca4rr<br />
jo . D'o=Ws: A R .parr . ixL .zlk, 1luyhod : L'S Dcps.-t•<br />
mc'tt oz Hdub and Huusa Servim, Public HaltS Sc .ice,<br />
OEfice of the Aswanr Sr_rrsrl for Hcalta, 0s cc on<br />
Smokinf and Healtti . US Gv .ammcnr Puncnj 0£'ice,<br />
1980 :0-3 :b-003•<br />
19 . Vem JE . .i :: pollvtioa sz s risk £car it lun3 arunr . A,w<br />
J F~ps.4,rsnl 1982 ; 116 : ,*2 - 56 .<br />
24 . Hiranei m, Iavciud Db . Sirtca 1fG, Lunr cuxsr<br />
motnliry u rciated to residcnce sad smoEint hi,mria . L<br />
Qjiirc tr-- :a . JNC! 1962 ; 23 ; 947 - 1001 .<br />
21 . Prs R . T,e mszcs-J diffcuaces bcnrecn tuvccnoids and<br />
rcrinoi,ij : metbodoloSical itapliacov for biocheaicaJ<br />
cpidr-:inlc87 . Csncer S.vs 1983 ; 2: 23 ; -40 .<br />
22 . D7atc:bc:y LW . icob WD . InhiDiiica d polyrytli .c<br />
ammuu hydrocrt:oo•induced ncr ;l :uis by auuaL7<br />
ocruuic8 indniu• C.r:ccesRrt 1978 : 31 ; 1410-3 .<br />
23 . S&co A . D"•Vorfis P . Skalkidis Y, Kaaouysani K<br />
Tnehopouloa D . .M dsslwio+e of tbr ~~urr.rsett of<br />
Tojaua-cosne! Lr ju4me Po(iciu o 1=C Me»eoer Suur .<br />
1941- 79d7. a rr?orr tc the Com ; ~n ar tat Jiavope:w<br />
Cot:nraunirus. AtIear : Furnpe lfa,nst Ciner., 1989 ;<br />
i41 -6+ .<br />
IS . :ussson Geae :zl. r2eliuraj rie NcsliL Conrreye,cut of<br />
Smoias• 1j Yssrr of Prorre .u : s&pon . Aodnille,<br />
Elar.iaad : US Deparr;a.car of HcJtti and 'tdurasn Ssrvicv,<br />
Public Hrlth Scnces, Centea for Disea,c CoouoL Cnce :<br />
:or Quonic Diacuc Pre+esci.oo snd Hclch Promoaoo .<br />
OE•- icr Smoicia{ and Hoalch, 19E9 : DHD-IS Publiazioc<br />
tCDC) 29-!•A 11 .<br />
25 . 6ro.naon RC. kcii JS . Kedc TJ . feqtyon SW, Psc! JA .<br />
Ls1t 6croa for sdcnoeusiooru of tbe luat . Am J<br />
E,ordes.~ol 1987 : 12i : 2$ - 34 .<br />
2G . Dals!.cr VA . Pickte LD7, Yason TJ u st ; The ralnrion of<br />
passive imokiag to <strong>lung</strong> ancer. Ca+c:r Rer 1996 : 46 :<br />
LlOt - 11 .<br />
27, Pcmhzca G . Hruber Z. Svracoa C . Pnnire rnaokins and<br />
dint aaeer in S .edish .amrrt, Ax f Fr~,r/e"tial 1917 ; 125 :<br />
17-24 .<br />
21 . Wu AG, Hcadcaoa 3E, Pikc MC, rt al. Smaki .ag and<br />
otDa ask fae:ors for lun8 ance : in .ornr . JNCI 1985 ;<br />
74 ; 747-51 .<br />
21<br />
i<br />
L
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
8
Koo, L ., Ho, J .H .-C ., Saw, D ., and Ho ., C .-Y ., "Measurements of<br />
Passive Smoking and Estimates of Lung Cancer Risk Among Non-Smoking<br />
Chinese Females," International Journal of Cancer 39 : 162-169,<br />
1987 .<br />
Koo, L .C ., Ho, J .H .-C ., and Saw, D ., "Is Passive Smoking an Added<br />
Risk Factor for Lung Cancer in Chinese Women?" Journal of<br />
Experimental and Clinical Cancer Research 3(3) : 277-283, 1984 .<br />
Koo and colleagues, in their 1987 case--contro7 . study of<br />
women in Hong Kong, included an assessment of workplace <strong>exposure</strong> in<br />
an accounting of total lifetime <strong>exposure</strong> to ETS . The<br />
concluded :<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
On the basis of our extensive life-history<br />
data, we were able to calculate the total<br />
years, hours, mean hours/day, and cigarettes/<br />
day to which the subjects had been exposed to<br />
tobacco smoke at home or at work .<br />
Despite such detailed accounting, we were<br />
unable to find a significant trend in the<br />
crude or adjusted RR for these 4 lifetime<br />
measurements of passive smoking .<br />
authors<br />
In a 1984 publication, Koo and colleagues reported a riskk estimate<br />
for women exposed at the workplace of 0 .91 ; this negative<br />
association was reportedly not statistically significant .
J .<br />
.1 . Ltp . Cusw. canoer itn_ I(1~ ttis<br />
LT'2-xT1<br />
Is passive smoking an added risk factor for <strong>lung</strong><br />
<strong>cancer</strong> In Chinese women?<br />
1-C, Koo' Ph .D . . J .H-C . Ho' M .D ., D .Sc ., F .R .C .P ., F .A .C .R .,<br />
D . Saw' F .R .C .P .A ., M .R .R .C . Path .<br />
6O".'rA%Mt N Co~iry M .liaw . U .lws+ry N Nons CAw4 N004 [wai<br />
s if . ~ N .D . lw.uiot N frdisCOtr 6%d Owrslofa. QwM tIisalah Narwl . NF a{ Crws<br />
s il. • N .D . l .a .uuu M Lh.t.a• Qwrn AisuaA Nrwul . Hw+[ KeRt<br />
XD f.ma2s btnt eranwr Paients .W =0 k..ltk7 Lhuitt .mtr .l4 w.v ircs~<br />
.itwed to ilsaiU7 snd euantJfr tl. r.rious aure. .I p.u .. seeokieq . ...ng<br />
Chinas (emil . la Hong Koeg . F« tl+s evervmokas- p .ui .v se}osurs h.o<br />
wa-tal roure.. (id .a .pre .u t. add u ebe{r ri.k . F.. tJ. .e•era+e .Ys.<br />
,ualltaav . asaes.roenu (.n,olt Ga"urt euetvnr . ss. .Acn Fsui .e esptuee<br />
tur+rd) . and qu+ociuti .e s.an .manu (bours . rasm inretuir7) she . .l r s:<br />
Q+iresac ditfsnnco 1~sTw .en cbe tat . (or pci .nu .nd .onrrols . M.r•wvt .<br />
Loes t .lscirt eti.W vut sto( rxtiaisd .iih ikither leveL of pusi•e sewking<br />
for tLs r.a M s .c+mokvs . T)ius. svr ru,dinp .ould usea, to inliaate<br />
tbac Faui .t smo{uru, ss u+ i .otsied f.nor . lid .oi lu .s ae 1r+lluence .n<br />
(s=al . luni ancc isadsnss in Hona K. . .4 .<br />
Recently, there has besn renewed dierussion<br />
on the possibie etfeeu of passive<br />
ssmokins on 1un= eaacer risk (5, s, 19) .<br />
ta paviouw studies oa tht possibility of<br />
incrmsed risk of <strong>lung</strong> <strong>cancer</strong> among wives/husbar-ts<br />
trolr, tlleir smok ;af spou•<br />
ses, the dau (2 . 9, 12, 16) were on]y bssed<br />
en wbe :her the spouse smoked (yes/no)<br />
witth no funher quslifiutions on whether<br />
the smoker actua .lly staoked in the pre•<br />
seace of the subject and for bas+r loaQ .<br />
Whero t qusstifiation * was done (S,<br />
17, 1i), it was bued on the eurrent spou•<br />
se's smoking habits . lt !s weU known that<br />
the eaxcinoYeoetic process of iateraal solid<br />
csacers tuually begfns 20 or more yurs<br />
beiore di.agaosis wben there might luve<br />
besa no e.zposuss frorn the eurreat sour•<br />
ee . Funhe :more . little account was taken<br />
of et.anges ia stabking habits or marria .<br />
re, or'the possibility of <strong>exposure</strong> from the<br />
work eaviron:aeat. Some of tseu pto<br />
Rsewi+tid lacuwry 14, tM+ .<br />
• t. .bw e.pw .n Lr eevrian .iw.l/ Y . sru.<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
blerns were raised by Harnmond a .nd St•<br />
likoff (11) but they have ytt to be ad•<br />
dressed by epidestiological srudie .s tA dtte .<br />
Chinese females in Hon= Kong hxve an<br />
avera`e annust.i age•sund.ardized ineiden•<br />
ee rate of 24 .1/100A00 tor <strong>lung</strong> <strong>cancer</strong><br />
(13) . This is aflong the highest rates for<br />
woraen in the world . In order to etore<br />
diroctly assess the possible role of passive<br />
smoking ia <strong>lung</strong> cs .acer development, a<br />
retrospective stvdy of 200 female <strong>lung</strong><br />
ancer patienu and 200 healthy district<br />
controls wu brrua in 1911 . Hong Kong,<br />
wit.h an average urban density of 2'I,000<br />
inlubitinis per square kilometer, and I<br />
sa' of average livinf space per person. is<br />
one of the most densely populated atess<br />
1a tbe world. It is, tturefore, an apprsr<br />
priate place to test the passive smolcing<br />
aetioiopal bypothesis .<br />
P .rieats and -setbodi<br />
Tl+ )00 lusi sanest }scenes sy6i .d wae htaes<br />
tA. ." ir *u•s+aumc iausmseo @( t br .nuJs<br />
.., z .7~
p . .ive ssnoking e}sic is Ckinss w.msa'<br />
lad. In addidoo to ever-smokers (S), therc re staokin` at botae (H), workytaca (iN') .<br />
were xIlosr who lud eohabitins rslsuves or both (HW') bad X.Rs oaly mtrSinally<br />
asnokinY in their presence at home (H) .<br />
or tDosr da.i.)y exposed at tbeir workplau<br />
for a auraber of years (W) . In Fg . I three<br />
tn u.-seetin t cirtJ cs La v e b .ea dra wa to<br />
0kovra sevctt possibie catcj orics aad one a- s+'I'' ""*'*"'<br />
4ol .ited circle (N) representinj those who<br />
lu .d aever beea ezposed to any of thcse<br />
stIular aourtet . Passive erposure ls de~<br />
aotez3 by the shaded area . and includes<br />
sidutrcam smoke hom lSOme or workplace<br />
To set wizether this qtulitativa method<br />
of usessmeat wou7d duc irninau higher<br />
risk Foups, all patienu and controls we•<br />
re fined into tac :, af these i d4fferent<br />
smoke <strong>exposure</strong> atejories and the odds<br />
ratios were caJculated (Table II) . It t8osr<br />
wiraing none (h1 represeot the standard<br />
witt a relative risk (RR) of 1-D0, smokers<br />
with no other source of ezposvre (S) or<br />
triu]tiple sources (SH, S' .' . 3HV,') had RR.s<br />
ranting from .2 .Sb to 5 .45, wheress nonamokers<br />
who were only esposed to pusi•<br />
Iva : saakad<br />
Passive axpoiure at vork place<br />
t4 1 • smult t+rrot,uV meso .ia .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
i<br />
T .kk II • Ralmiw tiio fRR! 1 .. AJJ.r++ . ersd.Jlr<br />
.ra*Mn<br />
o...... .. ..rn faau .a, i...sn r<br />
s a<br />
g u ~.<br />
1 ;u<br />
14<br />
SW<br />
~ 32 ~ AIt ' .Ri<br />
w. . .t a.o src<br />
s . s.us.rt,.~W,.s<br />
1<br />
1 : N<br />
s., . .a. .. ..rrr Nt..u e....1i a<br />
s•s:•sv .svs~ ty ~x s .xx•<br />
s-r .w u i, t .u•<br />
r u ar s .so<br />
' •SG .a.w,<br />
lassiv . •xposu :a ; ; hors<br />
i<br />
znti..: a.o s+a<br />
No exposuz• ca :aed
scm L .C. « ai .<br />
greater tharl 1•00 (tanjt 0 .l1•t3f), Whcn<br />
smokers aad tbosc oaly passivety ezposed<br />
were 57oupod (Table IIB), the 3tR of actire<br />
smokers was 323, and that tor the pas••<br />
aive smokers a lioa-sipifinslt 114 .<br />
Quanrij`3coriorl of prusrve t++sakilsp<br />
CYu .r detailed lntcrvicws ailovred us to<br />
e3tirna.ie the amounu of pusive smoking<br />
from vsrious piacen in terau of boun or<br />
ycarY (Table III), Smokm as a group<br />
had more ezposure to passive smokinr<br />
from others thin the never•smokers . Dr<br />
pendinj on ahe ur,it of messure :nent, whe•<br />
ther hours or years, we tound that araong<br />
the smokers, the patieau had rnore hours<br />
of <strong>exposure</strong> . but the controls had more<br />
yex :-s . Amot:Q the aever•smokers, the con•<br />
trnis acalaay had more hours or years<br />
ihan tbe pltueau, but these differences<br />
were miai.ma:. Hours per yr.ir was used<br />
as a meuure of inuasity of passive eorpo<br />
aurz . Overall, there was to tizzinca .at<br />
dittcreacc in ezposurn lev<strong>ets</strong> bsc.veea patier,u<br />
and eontrols, whether t,hey wex<br />
smoke,-s or asver•smokers .<br />
Tsbit itj • Avt+eyr eesv+RU"na 'asaw wi+een<br />
mvkr srrosurr ry ri .cr,<br />
/1a,a<br />
3 .ar.<br />
p.+ rr• ps v ..T•rn<br />
11<br />
•rtL..u<br />
73<br />
~ .er.lt<br />
N<br />
p<strong>ets</strong>s,<br />
f1<br />
M .~r.L<br />
W, t1 .l7f i1 .711 U .1f1 u .77/<br />
T.ar, It .f )t.l Z3 .7 L•3<br />
sz , ..+.aa. .<br />
/ .J77 t,Wr 2 .ttt l,Ml<br />
t.ar, , 3 .1 i .r e•• t . :<br />
SA . :ful Ywnu<br />
Me,<br />
t.a,<br />
a/ .711<br />
3•,1<br />
1:1 .1i!<br />
31 .•<br />
if .Ml<br />
ae, .<br />
ai .eli<br />
u,l<br />
awr+lr..r fff•/ 1t1•7 pT .O 1ti .t<br />
Since about 9011 of the tota .W aatounu<br />
of passive srrlokins car»e from the home .<br />
Table IV ahows the average eontriputian<br />
from each whabitinj relative who amokod<br />
!n the presence of the szabject• Ouly diretl<br />
tzposure was coustud. Husbaslds who<br />
amoked, but s4Sd tu+t ssxpose their wiru<br />
to passive smokiag for .uious tsssoas,<br />
aucb as tivfaf ovezseu, on mvellisiE }obs,<br />
etc ., wese llot included irl t!x sstimatiotu .<br />
From the C2iinese culttlral practice of ha•<br />
viag extended famS]y mcmbsrs living to<br />
getber, the fetma]c could bc exposed to<br />
her partau' cirsrettes or pipe whtn younj,<br />
to her busband's and in•laws' tobacto du•<br />
ring marital lfte, and to her children's ci•<br />
rarcttes when old . Atthouth in terms of<br />
hours/pcrson, parenu wert found to be<br />
a heavy source of sidestrearr, smoke, only<br />
a minority of patienu or eontrols wert<br />
to exposed• The most frcquent source was<br />
that rrom the husband_<br />
About 2/3 of the toul hours of tobae•<br />
to ezposurc were calculated from our<br />
dau to be from the husband's cirarettes .<br />
hoth cues and controls had ar averagc<br />
of about 20•000 houn of passive sxrsoicuig<br />
trom theis homes . to that to signii,cant<br />
ditfercncr in <strong>exposure</strong> levels waa fotsnd<br />
betwes:, them .<br />
TaIz IV • jwo•cY .r P.m .ti srrouet a 400" ,<br />
Iwtye •na: 4nr .,,<br />
LA3 pes*u t" wenL<br />
r • ewr,i• ., .r . r a+ ..,ip.., . .,<br />
a ..e.. 3v U .ul tu 3• .Ilt<br />
U<br />
,<br />
il .!•a tl<br />
s<br />
:1,76A<br />
1, :17<br />
A11in,.<br />
' LaduleJ wro SI srrin .u wt !I rwc»4 ruti•<br />
.w 'am''e arpos+r. I f RM7<br />
290<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
• 11•nl<br />
la<br />
U<br />
4,si1<br />
: S 11,t7/ p,/t2
Unlike the Louisianx ttudy (n, we<br />
fotmd tso asscciation of aa tncrsa.st to<br />
disk of ltl: g cascrr amonQ currcat amokess,<br />
su .tmokcri . or neveramoksrs and<br />
euterira or pateraa .l (yca/oo) amojda=<br />
Wilu.<br />
,pn.oftsnt tdstory a+a kistotojy<br />
AtnoAj the sver•staorers, thsre wu a<br />
prcdotataance of aquamous aDd ezaall al)<br />
types od It,lns tumoun, .+bereas the opposiu<br />
pattern of a predomiaa.nce ot adr<br />
ao:.ar-.iaoa~u was fouad for those passi•<br />
vtly erposed and the N eateYory (Table<br />
V) . There was no tipificar,t diiference<br />
ts1 etll rype dismbution betweea the pas•<br />
tively expoatd womea and those with no<br />
relr.llar orposure . The predornitunce of<br />
ade .nocarcinam:s in the aever•sraoked<br />
womea u atroup, rt=ardless of tAeir<br />
passive smoking history, has been rspor•<br />
acd sisewbere (I, 4 . 10),<br />
? .iY V . srw+"ns Miaa•t ..r .l.r.+etr<br />
s..s.{ Warr7<br />
l.il r7}t<br />
frw. .r. • ....r .. .uw •<br />
aril (r11 Lrp L.11<br />
9-wt MrM NS (11H7) l/t (3+/tJ)<br />
l"+t•" a~uo Ai1 CU/7f) 3n (i6lit)<br />
ar* i71 ( 7/tf) I71 l17/1f)<br />
Rirk smon j xever•rnokerr<br />
We have easlier :hown that the averaRe<br />
total amouzt of bours or years of pu :ive<br />
tasokla= among the . never•smoken wa,<br />
stot signif•ica .atly dlffereat berwrea patirnu<br />
and controls . Wc also did not l5s1d<br />
a hiiher 3LR amonj patients with passive<br />
sxposure levels of > 35,000 hours (3 botus<br />
12 ttsin ./diy s 30 years) than thou with<br />
lower ezpotures (Table VI) .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Hwhs emokis~g tuk h Chir,a. . v.e+tn?<br />
TJk V1 . RR N 1wy Nwrn w+R d rWV&0WAAen<br />
tt /rwli .l rww .eWar<br />
ft-"n Na,at sMn.l . a r +1M<br />
n<br />
!9<br />
s~<br />
Y LM<br />
{/w,<br />
tt l.il t1 .<br />
~t<br />
s~. .~ f .. .~ ..<br />
t+<br />
k<br />
11<br />
11<br />
1 .13<br />
t .1 .<br />
OI .M<br />
t . . .#<br />
t tsj= rat<br />
> Isl+CO /n..z<br />
It tt poutble that the lsr0sehial CIIu•<br />
enaa is more rusceptibie to casrino ;osu<br />
before adulthood tlla.n later ln lite . Table<br />
V71 sumtmarized our data on a .gs when<br />
pusive ex-+osuse t;tarted for the euver•<br />
ataokers . There was no siLnifiea .nt -stiffe•<br />
re.ace b
KAo LGscai.<br />
kta= oaaoer . To s+e if psuivs smokizg<br />
.dds risk to active smokers, the risks for<br />
4ht smokcrs (< 100 k ; tobacco or 14<br />
µtk rrs .rs) witb low or sto passive ezpossum<br />
(< 13,000 hours or 13 bouss/dsy a<br />
3C nars) asd tbose smokin: sdmllar<br />
amaus:u but witb bsavy passive smoke<br />
scposures were compared Cfabie YIII) .<br />
The same eomparison was applied also to<br />
the besvy amokers (> 100 kg or 14 pack<br />
?ears) . We found aot only ao iacsrase but<br />
aa acYtul desrease it the risk for botb<br />
ifgitt aad heavy emokers rritb heavy passive<br />
ezposurs eompatrd to tbose with ao<br />
or 1ow expdsure. There was oa]y an (ncreafe<br />
in the risk related to the kvels of tbeir<br />
own ciruetu consumption . This result<br />
was also found by Correa at LL(3) .<br />
7tb4 vt11 • RX M r .wk ." .iIV wJ .•ubw<br />
ru„w erewar . .<br />
~7t+ htass. wer.L IL<br />
t :: `+s-~'^<br />
. . :, .."r.". ~ . M<br />
uac ~.+.., .. .,<br />
i5 .> rra.r11 .ta N 1~ 7 .4i<br />
Sa. 07 so w+suti<br />
W~TY K[k<br />
~Mnt ,<br />
a.w tu u<br />
iJOt?ts .".cnv '>la7tI ri.nro<br />
' t tlAOO wown ' t tl1q0 howl<br />
Disctinsioa<br />
Ia t2t9s retrospettive study on the pos•<br />
sible influence of passive ststoking on the<br />
high iacidence of <strong>lung</strong> taaeer it Hong<br />
Kong Chinese feaules, we have attempted<br />
to identiS;+ and quantify various sources<br />
and typa'of tobacco <strong>exposure</strong> among 200<br />
patieats and 204 district controls . We have<br />
Umited our dau prsseztation to show oaly<br />
those facton r=levatt to the ittue of<br />
passive smoklbt . AA more deu3led descripiSon<br />
andn disctusion of active smokint as<br />
212<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
a risk factar was presented alsewbere (is) .<br />
The appareat lack of aa as :ociuton<br />
betweea pascfvt smoking aad the " of<br />
lun; nacer in our study may be due to<br />
possIbilitiss whlcb ocruz because passive<br />
amokinj msy be ody t ary Mrah esrri•<br />
Dozen, whose affect may be coaosaled by<br />
ot2ter factors that play a role fa a melti•<br />
factorial and multisuge ardoloty. Among<br />
the femaJe aeYSr•uaoksrs, lnts•rvaaint<br />
factors mi=bt eause an ovessludowirit or<br />
a protective effett (e{ . brnachial irrita•<br />
t(on, dictary s ot betacamuae)<br />
. These factors fn Hong Kaad are li•<br />
kely to be ditfereat from those fn Japan<br />
(12) . USA. (9, 16), or Grerce (17, 1f), and<br />
this differr.ace may ezpiain our different<br />
sesults . The possibiliry that the ; dose•re•<br />
spatue cusve resembies a lotistic it shs•<br />
pe . such that c there is a dose greater<br />
than srra which produces zero rrspoase •<br />
wu r•onsidered by Hasnmond and 5eii•<br />
koff (11) and may be opiratits= bere .<br />
Cen.isJy the lack of an iacrosed risk<br />
for the active smoke :-s from passive tmokiag<br />
. whicli was also found by Corrsa ct<br />
ai . tS) . Would aex .= to support the poesibility<br />
that the effecu of active smokLzg<br />
or, tadeed, otlser taotars ytt to be iden•<br />
eifled F=17y overshadowed ehc art ;ino•<br />
`eaic acuon of passive sMoking .<br />
This, however, does eot iirtply that passive<br />
smoking is iabocuous, as It may con•<br />
tr;bute an added risk of other respiratory,<br />
and cardiovascular diseases (i, 14, 16) .<br />
The possibility of other factors like diet,<br />
previous Eistory of respiratory diseases,<br />
occupationsl wtpostues, ase of istAalaau,<br />
etc .• overshadovving or inhibiting the ef•<br />
facts of passive smoking on the risk of<br />
<strong>lung</strong> <strong>cancer</strong> among aever•smoked females<br />
in Hong Kong and also the roles of these<br />
factors in the arcinogenesis an beint<br />
investigated.<br />
It is hoped that more direct assessmestt<br />
of passive smoking by other wor•<br />
ksrs !n other areu ean shed atore light<br />
oa the passive smoking eoatraversy .
1<br />
AM..4adM..ww<br />
1Y. r4h s ssr.r am j* .doad . .d *a.b r YK<br />
lW3ir'{t{ VGOBCCO6! Wtl "ridtY11 fK Aft1 (Mfl<br />
` Ali/ }fB/om am HM1/ r.N{ AJ/4r•JiEYf 66CtT7 .<br />
a .d tLs losaxh .+d Gcfercnc. GMtl C.ftaaa.r<br />
.r tlK M .d;na7 r.aAe7 K•"Amb crvu Awe .+<br />
4110 Usi .aruh' .! H.nt lC.ut f.r fi.a+dal wrtwrc:<br />
hd .ror CJC Mok. Dn . MX. {ac. KX. La . M .7<br />
w .i, v .C. Ckait. L Hou. tx tiw . C .w . Ckac<br />
id X.T . Tiua ad t'iur 1[. Asuinr Mr dtir<br />
.d•.is rd 1 .* 1tlr . C- Cir Ma . C . T.nt ..1<br />
1i4. N, i.n f.r Ldt 1. Lu dl .criao .d au)7-<br />
,it : r1 Ma . 0 . Lsn. Mta. T . Lr ad Hi A.<br />
Chow f« .asu,isl w1tw.«<br />
Rdtrssm..<br />
l . Ch&n W .C . Ca)knan: M .1 . Funj S .C. Wo H .<br />
C- Imncdial mnter is Hon! Krn! 1f7b1117 .<br />
Ir. I . Cu,car, 3!: It2•!!2, 1979 .<br />
i pua W .C_ F=8 s.C_ Lvu rncn r re,<br />
eook .rr ie Honj Koag la. Gnismnann L. Itd .) .<br />
Catxa Camotitn . Voi . 7 . Cuetr toidemiolorY .<br />
trunjtrt/Nr. Y.rk: Gmru• F'ucAa V.rtaj . tl+.<br />
241 . tit2.<br />
l. Man w .C . M .cLeaaata L : Lia nr+cer M<br />
Noat fCont Cau,.u .orulirt a+e kiiMtopu)<br />
tT" . tKStl12 . k . 1 . Catsa . ~! : ?212~) .<br />
1f7l .<br />
• . Caotrr D .A . Cnru AJt.. >iwroc KA: h+•<br />
a .ry .Ucsaa . K de iamj i. ranr,otas.<br />
AreL In .iroe. Hni,A. 16 ; 3K4C0 . 1944 .<br />
f. Corr. F_ Picrle LiV . F.n"m 1L 1.ta Y .<br />
H.maal W . : Fuai .t seoY,iaj .ed hmj oanosr .<br />
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Iru . J Cancer: 39, 1ti2-169 (1987) ~. . P<br />
0 1987 Alan R . L.iss, Inc .<br />
MEASUREMENTS OF PASSIVE SMOKING AND ESTIMATES OF LUNG CANCER<br />
RISK AMONG NON-SMOKING CHINESE FEMALES<br />
Litsda C . Koot, John H-C . Ho~, Daisy SA'w3 and Ching-yet Hot<br />
il3ept of Communitv Medicirte, Univrrsirl of Ho+tg Kn+t ; . Hong Kong : 2Radiwhtrapy Drpr ., 6aprisr Hospiral, Kowloon,<br />
fa'ong Kong : and 3/ruriswe of Parholog) . Qurrn Efi ;ehrrh Hosptrcl, 14jlir Road, Kowloon . Hong Kong .<br />
.<br />
.<br />
.<br />
t.Hetime e :powrss to enviro~nm.ntat tobacco smoke from 28 .t}00 inhabitir,ts/km2, with tmly<br />
the home ac workptaci for tY "rsever-smoked" ferrule <strong>lung</strong> a{uce per person .<br />
eancer patienu and 137 "t+ev.rsrnoked " district contr-alt were<br />
S m2 of available living<br />
•stimated in Hong Kong to a .ueu the possibie causal rotationship<br />
of passive ,mokint to <strong>lung</strong> tincer risk . llelat}.e risks<br />
MATERlAL AlJll MET1fUDS<br />
based on the husband's unokint habits, or lifetime estimatas<br />
of total yean, total hours, maan hoursiday, or totsl ciraraest<br />
day unok .d by aach houuhold smoker did not show dosa<br />
rsponse rawta . Similarly, when such catetories as mean<br />
hours.~day, or earlier age of inicial eapowra, were combined<br />
with Ygan of expoture, there were no apparent Increases in<br />
From 1981-3, E8 never-smoked female <strong>lung</strong> <strong>cancer</strong> patients<br />
and 137 never-smoked female district controls were interviewed<br />
as pan of a larger retrospective study of femalc <strong>lung</strong><br />
<strong>cancer</strong> in Hong Kong covering 200 cases :nd 200 controls In<br />
the orig nal study . pauents were matched with an equal numbtr<br />
relative risk . However, when the data were sepe=ated by of healthy controls by age (f S years), district of residence<br />
histological type and location of the primary tumor, it was (N-34), and housing type (pubGc or private housing), the<br />
asen t.hat peripheral tumon in the middle or bwer bbes, or, laner being in indication of soc)o-economic status Det3ils of<br />
fess strongly, squamous or smalt-cell tumors In the middle or<br />
}ower tob*s, had incrsuint ratauve ritkt that might lndicate<br />
some assotiatlon with pauive srt .ohin= eaposure .<br />
subject selection, <strong>lung</strong> <strong>cancer</strong> histological typing, and method<br />
of conducting the interviews have been discussed elsewhere<br />
(Koo et al ., 1983, 198A) . Never-srrwked subjects wrre defintxl<br />
as those who had smokeA less than 20 cigarenes ip the pasi .<br />
Epidemiologieal dsu linking passive smoking %kith <strong>lung</strong> All dau on ~assive smoking <strong>exposure</strong>s were double-checked<br />
<strong>cancer</strong> among non-smokers have been controversial Six studies<br />
(Htnyama, 1981 ; Trichopouios ei al„ 1981 ; Correa ci al .,<br />
1983 ; Knoth et al ., 1983 ; Miller, 1984 ; Garfinkel ri at ., 1985)<br />
found significantty elevated relative risks (RR) in the range of<br />
2 .0 to 3 .5 based on the smoking tubits of the spouse . Five<br />
other studies (Garfsnkel, 1981 ; Kabat and Wynder, 1984, Chan<br />
and Fung, 1982 ; Koo ei af ., 1984 ; Wu cr al . 1985) two of<br />
which were conducted in Hong Kong, did not find significantly<br />
elevated RR from inhalation of sidestream tobacco smoke<br />
Four of these epidemiological studies (Hinyama, 1981 . Trichopoulos<br />
er al ., 1981 ; Garfinkel, 1981 ; Chan and Fung,<br />
1982) defsned <strong>exposure</strong> solely by two questions : whether the<br />
spouse smoked (yestno), and the number of cigarenes smnked<br />
per day by the spouse . Five other studies (Correa er a1 ., 1983,<br />
irSiller, 1984 ; Garfinkel ei ol., 1985, Ksbat and Wynder, 1984 ;<br />
Wu er a1 ., 1985) aJso included questions about whether involuntary<br />
smoke <strong>exposure</strong> hnd occurred at work (yes/no), and/or<br />
whether the parents has smoked (yes/no) . Such data seem<br />
rather crude indices of <strong>exposure</strong>, providing only very indirect<br />
iaforrnafion on tbe 6KTrer add amount of exposurc . Funher•<br />
morc, altrtough spcntse(s), parents, or co-workers might have<br />
smoked, the actual degrte of contact of the non-smoker with<br />
tttese smokers could have been very low, or even nil (Friedsrun<br />
ei a1 ., 1983) . In our detailed sasdies (Koo ei at., 1983,<br />
1984) of passive smoking <strong>exposure</strong>s, smoking parents or<br />
spauses were sometimes rocalled as inflicting litnle or no <strong>exposure</strong><br />
on the sub}'ut . In those cases where, for example, tfu<br />
husbard smoked but lived aepuated from the wife, then our<br />
study counted such wives as unexposed subjeru . Among our<br />
never-smoked subjects, this was found to be true for 3 cases<br />
a.ad 3 controls .<br />
In order to asseu the possible qusal relationship of passive<br />
smoking to <strong>lung</strong> eancer risk, dau from detailed life-hisrory<br />
<strong>exposure</strong>s ttut were elicited in intensive 1 .5- to 2-hr taperncordad<br />
interviews of never-smoked female <strong>lung</strong> <strong>cancer</strong> cases<br />
and district controls havc been ana)yxed . Emphasis is placed<br />
on the eonsist<strong>ets</strong>cy of the data, the strengths of tltc RR, and<br />
whether dose-tccponse relationships were present .<br />
with other data elicited in the ltfe-history interviews, espeeially<br />
residential pancrns since birth (i,ewhere she) liver :,<br />
type of housing . number of rooms, number of eo-habitants,<br />
etc ), occupatloru, and rnanul life to reduce errors in estitnating,<br />
<strong>exposure</strong> levels<br />
Among the txver-smoked subjects, the mean age of the<br />
patients was 57 .8 (so 10 .81) and that for the controls was 59 .3<br />
(sD 9 .94) This umple included 60 who were widows usd 3<br />
who had never mi .rried ; eone had rrtarried more ihan txsct .<br />
In the design of the interviews, separate data were eallectad<br />
to take into account that within the life-histories of the subjecu,<br />
sidestream tobarcro smoke could originate from : (a)<br />
different people who stnoked in the presence of the subjest ;<br />
(b) different places frequenud by the subject ; and (c) different<br />
types of tobacco . Persons who smoked included related and<br />
unrelated members of the household, and even co-habituns<br />
who shared an apartrrtent unit (if their tobacco smoke was<br />
tooticxd b) the subjea) . It was difficult to quantify expoi ;ilre<br />
levels from places that could have varying daily amounts of<br />
environmental tobacco smoke and were occasiorully visistti<br />
by the subject such as cinemu, while playing majong, or in<br />
t7anspon vthicles . This analysis will ottly take into account<br />
<strong>exposure</strong>s that remained relatively regular during the lifetttnes<br />
of the subjects i .e . from <strong>exposure</strong>s r.l borne and the workplace(s)<br />
. Among our subjects, tobacco srrsoke mosdv otiS'saued<br />
from cigarettes smoked by household members, ared<br />
from pipes (water and regular) smoked by parents or in-laws<br />
In addition to data based on the husband's smoking habits,<br />
4 other measurements of passive smoking were evaluated : (a)<br />
Ioul ycars ot <strong>exposure</strong>, (b) total hours of <strong>exposure</strong>, (c) mun<br />
hours/day of <strong>exposure</strong>, and (d) total cigarettes per day snwked<br />
by each htwsehold member weighed by their years of <strong>exposure</strong><br />
. These rrxasures should be a more accurate ref)ecuott t~<br />
past lifetime expasures than simple ques :ions based on whtthc,r~<br />
the spouse or pesenu sawked (yes/no), or whether envitvrt~<br />
menul tobacco Ismoke was encatntered in the workplace (yen<br />
no)<br />
'ihis srudy of thc effects of passive smoking is panicularly<br />
pettinent to Hong Kong because n is one of the most crowded . ~<br />
urban ettvironrnents in the world . Its urban dertsity avetases Recoivad Jux. 24, t4a6 tad in ycvised fotm Sryternbar 19, t9iG la-A<br />
~<br />
~<br />
~
.;.:~: . ~.. :..,.x<br />
f.t_LSrvE StAGK.rNG rN CHINESE FEfdA1 .FS<br />
The toul years of <strong>exposure</strong> were derived from adding the<br />
years during which tobacco <strong>exposure</strong> occurred in the home or<br />
workplace . Exposures of 6 or more months were rounded off<br />
to the next year ln the home environment, household smokers<br />
were ottly counted if the subject necalle.d that they had smoked<br />
in herptc sencc, Where <strong>exposure</strong> was concurrent, as in the<br />
ase of xtxxh parents smoking . or <strong>exposure</strong> occurring at the<br />
home usd workplacc, then the years were no+ added<br />
The tota] hours of <strong>exposure</strong> were calculated by multiplying<br />
the average hours/day of <strong>exposure</strong> by the yean of <strong>exposure</strong><br />
from each househoJd smoker, or thc amoum of <strong>exposure</strong> u<br />
each workplLce . Each of these sources of expausrc wu t}xn<br />
added together for each subject The hours were not added for<br />
<strong>exposure</strong> to simultsneous smokers, For eumplc, a husband<br />
and son smoking at the same time for 1 hr would only be<br />
counted as 1 hr .<br />
The mean hours/day of <strong>exposure</strong> were derived by adding<br />
thc hours/day of home and workplace <strong>exposure</strong>s and dividing<br />
this figure by the age of the subject . This figure approximates<br />
the average number of hours of <strong>exposure</strong> per dzy experienced<br />
by the subject, spread over her lifetime .<br />
A weighted average of the toul cigarenes per day smoked<br />
by each household member was ealculated from the summa•<br />
tion of the usual number of cigarenes smoked throughout the<br />
day by each household member muhiplied by the years that<br />
each lived with the subject, divided by the total years during<br />
which eiguene <strong>exposure</strong> had occutTed in the home This<br />
figure rnal give a better tndication of the intensity of cigarette<br />
<strong>exposure</strong> tn the borrx than one simply based on the number of<br />
cigarenes smoked per day by the husband, becaus.e it accounts<br />
for other household smokers and the years that the subject was<br />
exposed to each smoker . This figure excluded <strong>exposure</strong> from<br />
pipe smoking and the cigarene consumption levels of coworkers<br />
be.c.ausc of difficulties in quantifying tbosc amounts .<br />
Of the 86 patients, 83 were typed histologically . Among the<br />
remaining 5 usrs, biopsy or cytologic materials revealed that<br />
maJignant cells were present, but they were too undtfferentia•<br />
ted or unspecified for categorizuion by cell type Chest radlo-<br />
U phs were examined for all cases, and the site of the prinury<br />
g tuRror was classified by iu location in the bronchial tree,<br />
and whe2her it was centrally or peripherally siruated, In this<br />
analysis, the IingUla was classified ascq uivalent to the middle<br />
lobe, and peripheral tumors were defined as those located<br />
beyond the segmental bronchus .<br />
Sutistiul analyses included the calculation of RR as the<br />
crude or adjusted odds ratio and tests for trend (Breslow and<br />
Day, 1980) . Adjusted odds ratios were euirtuted by the tue of<br />
a conditional logistic regression package, PECAN, (Lubin,<br />
1981) which was based on N :M matching by strata defined by<br />
district (N- 34) and housine type (public or private) . To take<br />
into account the effects of potential confounders which affected<br />
the Rk estimates, adjustments were made for age (
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F,ouR€ I- Measurementu for passive smok)ng lfnd RR for <strong>lung</strong> ancer<br />
'Adjusted for Rge, number of !(~c b(nhs . cchool nF (*/-) and<br />
years since <strong>exposure</strong> to ciEarmc :moke wsxd in the t,omc or workplace<br />
p C 0,05,<br />
PASS7VE T).1O1(.JNC (N airNESE FEM/.LES<br />
the squamous or small-celf <strong>lung</strong> tvmon than anwng the adenocarcinoma<br />
or large-cell types (Table Vl) . This was especlatly<br />
tsve for the adjusted RR in the former g•roup, as 3 of the<br />
4 measurcmen(s consiuently indlcated irscreasing risk with<br />
increasing ezposure .<br />
lvcvrian by lobe<br />
Eighty of the cases had the rnain tumor residing in one of<br />
Ehe lobes The remaining 8 cases, with primary turran in the<br />
right or lefi main bronchus, or in the rlght intermedius region,<br />
were too few for analysis . Calculations of the F:R rhowed that<br />
none of the crude or adjusted values were signifuxnt for<br />
upper-lobc tumon (Table Vll) . For the middle or lower lobes,<br />
all of the adjusted RR were in the comparatively higher range<br />
of 1 .9-3 .5 for those with some passive ezposure~ t~ .lorr,over,<br />
for 3 of the <strong>exposure</strong> mcasurcments, toul years, hours/diy,<br />
and cig.renes/day, the confidence intervals for the cnsdc and<br />
adjusted RR indicated some borderline cignificant values .<br />
However, none of the trend aruJyses for the lobe dau cunc<br />
out significant .<br />
TAILE Vt - MEASVREMENTS Of TASSivE SMOYJNG AND RR FOR LVr+G CANCER )Y }05TOL .OGICAL TYTE<br />
NWmisr o( eue"<br />
rumecro(<br />
«x.rdr<br />
L,u.mo.. .r rnahcen Adcruc ecrcwt, sr Yr}.~ll<br />
Rl('ttl! C()<br />
ItII'rflS Ctl<br />
Nre'en ef u.ei/<br />
vmtcr d<br />
eo .rol,<br />
RA'r157 Cll Rl~~ RSt t71<br />
Toul yurs<br />
0<br />
1-26<br />
7/40<br />
10,46<br />
1 .00<br />
1 .24 t0.37, 5 ao1<br />
1 .00<br />
1 .58 (0 .37 . 6 77)<br />
12/40<br />
17/46<br />
1 .00<br />
2,11 (0 S4, 3 .74)<br />
1 .00<br />
2 .07 (0 .64 . 6,71)<br />
27+ 151 51 1 .68 (0,47, 5 .79) 1 .12 (0 .49 . 6 60) 11151 1 .90 (O .S1, 3 .27) 1 .43 (0 .51 . 4 . 02)<br />
Toul hours<br />
(in hundreds)<br />
0<br />
1-150<br />
15) *<br />
7/40<br />
12/56<br />
13/41<br />
1 .00<br />
1 .22 (0 .34, 4 .71)<br />
1 .81 (0 .52 . 6 .54)<br />
1 .00<br />
1,40 (0 .34 . 5 n)<br />
2 .04 (0 .53, 7 .i;5)<br />
12/40<br />
1g/56<br />
16/41<br />
1 .00<br />
1 .07 (0 4E . 3 .05)<br />
1 .30 (0 .59 . 4 .02)<br />
1 .00<br />
1 .70 (0 .55, 5 .20)<br />
1 .57 (0 .55, 4 49)<br />
HoursJ day<br />
0 7/40 1 .00 1 .00 12/40 1 .00 1 .00<br />
f<br />
166<br />
PltlSimpllp[ripriCrtll ioCYNIOIr<br />
KOOETAL,<br />
Among the 85 determinable ca.ses, 46 had peripheral rumors,<br />
and 39 proxirru1 tvmors . Ah}augh only the crude RR<br />
of 2 .00 and adjusted RR of 3 .52 (or 1-19 cigurnu/day were<br />
slightly signif3cant for the proxinul rumors, in general . all of<br />
the crude and adjusted RR for the pcnpheral wmors were<br />
"ter than 1 .00 rl'able Vlll) .<br />
Hisrolog ;cn! typt and location<br />
In order to see whether any particular combination of histological<br />
rype, lobe, or proximalrperiphenl loution of the ru•<br />
trwr would result in stronger dose-responsc patterns by the 4<br />
lifetime measurcments of passive smoking RR were analyr.ed<br />
for the 12 possible l .l combinations . We were unable to<br />
segregate the cases into any frner ategories than 2 of the 3<br />
groups because of the small resulting number of cases for<br />
analysis Space does not allow tu to present all the ubles, but<br />
the best combination was that of peripheral tumors in the<br />
middle or lower lobes (iable IX) . Among the RR, significant<br />
or nearly significant figures werr found for the crude or<br />
adjusted RR relating to at least one of the <strong>exposure</strong> utegories<br />
for each rype of ineasurement, Moreover, the adjusted RR<br />
tended to range between the relatively high values of 6 .5 to<br />
18,7 for thosc with some <strong>exposure</strong> (Fig 2), and most of these<br />
were significant or nearly signiGcant . None of the trend tests<br />
came out significant, but this and the tendency for the higher<br />
levels of <strong>exposure</strong> to have lower RR than the low levels of<br />
<strong>exposure</strong> may have been due tD the small number of cases<br />
(Nw24) .<br />
Akhough not as apparent, squamous and small-cell <strong>lung</strong><br />
<strong>cancer</strong>s in the middle or lower lobes (Fig 3) also seemed to<br />
show some positive association with passive smoking There<br />
were only Ig cases with this type for analysis and none of the<br />
RR or tests for trend were found to be sutistically si~ndicant<br />
. Yet it wu promising to su that all the RR with<br />
(Table X)<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
sonu <strong>exposure</strong> were greater than 1 .0 . Among the highest<br />
<strong>exposure</strong> levels for the adjusted R .R, values as high as 7 .0<br />
were found for totzJ hours, and 6 .2 for hours/day .<br />
DtsGU SStON<br />
For comparative purposes, tht rtwne comrrwnly used mu•<br />
surernenu of passive smoking based on yes/no tlttestions of<br />
whether household co-habitants (husband, childhood/aefulthood,<br />
or others) had smoked, or on the number of cigarrnes<br />
the husband smoked per day, were pn :sented . Only the crude<br />
RR of 2 .37 (95 Te C1 :1 .03-5 .91) for husbands smoking 1-10<br />
cigareues/day was of borderline si=rtifrwtct and txme of the<br />
adjusted odds ntios were signifscant at the 45% probability<br />
level . Thers was liale indication that increasing kvels of such<br />
<strong>exposure</strong> led to increased RR .<br />
On the basis of our extensive life-history data, we were able<br />
to calculate the total years, hours, rrsean hours/day, and cigareucs/day<br />
to which the subjects had been exposed tn tabacco<br />
Imoke a1 home or u work . Our esuimates were based on the<br />
tanderstarsding that the household composition of each subject<br />
would change as she progressed through the life-cycle of birth,<br />
childhood, adulthood, marriage, nwtherhood and, for 27%,<br />
widowhood . We also included <strong>exposure</strong>s from each workplace<br />
at which the subject had worked for at least 3 months . In our<br />
adjusted RR, the eficet of cessation of <strong>exposure</strong> to passive<br />
amoking was accounted for by ptming in the years that expoture<br />
had ceased at home and/or workplace as a corttinuotu<br />
ncgreuor variable .<br />
Despite such dctailed aocouruing, we wert unable to find a<br />
sigru fiunt trend in the ensde or adjusted RR for tixse 4<br />
9ifuifrre moasuremcnrs of passive amoking . Althoug3t the RR<br />
for the imcrmediate level <strong>exposure</strong>s of hours/day and cija-<br />
sY<br />
It .Oo<br />
12 .0<br />
6 .60<br />
4 . 00<br />
2 .00<br />
t .oo<br />
0<br />
.<br />
Nont LoM<br />
Exposur . Lrv .is<br />
High<br />
Total ysars<br />
Totat hourr<br />
tiourslnay<br />
Ci9 /day<br />
Frouee 2- Measurements of passive tmoking and RR for periphen :<br />
<strong>lung</strong> earscen in the mddle or lower lobes, A,djusted odds rauo,<br />
Y w<br />
!<br />
9 .00 .<br />
6 .00<br />
5 .00<br />
I<br />
:<br />
S<br />
r 3 . 60<br />
3 .®0<br />
1 .00<br />
Mon. • Low<br />
Exposura L.v .ls<br />
High<br />
Ftauat 3- Meuursments of passive smoting and RR for squamau<br />
and amall-oell <strong>lung</strong> ancer in the middle or lower lobes . Adltwnd odds<br />
eatio .<br />
N<br />
rettes/day were signifrcant, e}x RR at the highest levels of ~<br />
<strong>exposure</strong> for these two variables fell to a non•significant 1 .0• ~<br />
1 .2 . In fact, the RR for the highest exposurc levels for 3 out f-M<br />
of the 4 measurerrxnts were below all of those with lower<br />
expowru, ard ranged from a very weak 1 .0 to 1 .4 . On the ~<br />
other hand, etaoxt of the crude and adjusttd RR were jreatrr<br />
ilun 1 .00 .<br />
11 "1<br />
CA<br />
~
fASSIVE SMOKING IN C'11)NESE FEMALES 167<br />
TAILE VI11 - MEASUREME"l7S Of PASSIVE SwOK1NG AND tR FOt LI~NG CANCFJt !Y LOCATION OF TVMOR<br />
hnp/Ynl<br />
Wn1ar M crr,'<br />
e..r~c, e( roe .ra, RR' eri71 Cli RR~ (151 Cfi N-0cr d<br />
ar~w,rr r1 cav w,<br />
heasr+sl<br />
(1SI Ci) . . . R!
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
168 KpOETAl .<br />
Measurements based on increuing intensity of <strong>exposure</strong>,<br />
defined as increasing years (or hours, or cipretus/day) by<br />
mesn hours/day of exposun, also did not indicate a doseresponse<br />
relationship Likewise, the analysis of toul years of<br />
<strong>exposure</strong> with age of <strong>exposure</strong> did not suggest ehat arlier age<br />
of initial <strong>exposure</strong> and increasing years of <strong>exposure</strong> led to<br />
higher RR . it wu troubling to find stut in both rypes of<br />
analysis, the RR for the lowest amounts of <strong>exposure</strong> were<br />
among the highest values .<br />
Dalhamn et al . (1968) noted from their study of the retention<br />
of cigarette smoke components in human <strong>lung</strong>, that waterinsoluble<br />
volatile compounds and particulate maner from eigarenes<br />
tended to be deposited primarily in the deeper parts of<br />
the respiratory tret, Sina aderwcarcmorru is predominant<br />
among non-smoker <strong>lung</strong> <strong>cancer</strong> cases (59% of our typed cases)<br />
and it is tencrYlly a peripheral tumor, we wanted to see<br />
whether the passive smoking measurements would exhibit a<br />
more consistent pattern among the adenocarcinorna and largeall<br />
types, and/or among the peripheral tumors . In general,<br />
the pcripheral tumors as a group showed stronger dose-response<br />
results than the adenoearcinomu . •<br />
The RR for total years, hours, and hours/day measurements<br />
of squamous and snull-cell <strong>lung</strong> tumors indicated consistently<br />
elevated risks with increasing <strong>exposure</strong> . This panern was not<br />
found (or an) of the adjusted RR for adenocarcinorna or largeeell<br />
<strong>lung</strong> <strong>cancer</strong>s . This association of histology with passive<br />
smoking is also suggested from previous studies by Trichopoulos<br />
er al . (1981) and Correa er al . (1983),<br />
Analysis of the cases by the lobe location of the tumor was<br />
done to sce whether the primary tumor resided more frequently<br />
in the upper lobes than in the lower lobes . This is<br />
because it is known that when dust is inhaled, it first enters<br />
the upper lobes where much of it is deposited . and then travels<br />
down to the lower lobes (Time, 1980) Furthermore, it has<br />
been observed (J .H-C . Ho, personal observation) that up to<br />
half of the Hong Kong adult population have radiologically<br />
evident scars on the upper lobes of their <strong>lung</strong>s Most of these<br />
scars are due to previous tuberculosis infection Since "<strong>lung</strong><br />
ancer is more common in the scarred and chrontcally diseued<br />
<strong>lung</strong>" (Stone er al ., 1978), we were interested to see whether<br />
the lobe data would subsuntiate any of these possibilitiesln<br />
fact, 37 of the <strong>lung</strong> ancers were found in the upper lobes, and<br />
43 in the middle or lower lobes . The results from the RR<br />
estimates from the 4 types of ineuuremenu did noa show the<br />
upper lobu to be more scnsitive to eavironmental tobacco<br />
smoke .<br />
Wynder and Goodman (1983) suggested that lun u»cer in<br />
non-smokerslvu more likely to occur in the periptery of the<br />
<strong>lung</strong> . This wu found in our smdy, as 54 % of the determinable<br />
cases had peripheral tumors vs . 46% with proximal tumors .<br />
Moreover, the pattern of RR with die various rneuurements<br />
of passive smoking indicated that peripheral tumors seemed to<br />
exhibit better dose-response RR than proximal tumors .<br />
14'hen the RR were alculasod for die 12 pouibk 1 :1 canbinations<br />
resulting from histological type, location by lobe, e+t<br />
proximalp /periplseral txsmon, the hifheu RR were found for<br />
pen tKral tumort in the rniddk or bwer lobes . Signifieant<br />
adjusted RR as hith as 1E .7 wett fouad for some of shese<br />
measurements . Att~ough RR at die bwer doses tendod to be<br />
higher dun tfut for the hig3ser doses, the dau were consistent<br />
Yt that all the RR for ttwse with some <strong>exposure</strong> were much<br />
~rca ter tt~an 1 .0, and the adjusted RR for at least one of the<br />
itR fot erchtype of ineasurement .ras ttuistially significant<br />
or ocarly sitnt'frcanc,<br />
7tx RR analysis for aquunous and small-cell 1ung <strong>cancer</strong>s<br />
in the middle or lower lobes also appeared somewhat better<br />
ttun the others, with tocal hours and hours/day muzuremenu<br />
alsowing some dose-responu panern . With the above two<br />
combined analyses showing some promise, perhaps the best<br />
RR would have been obtained if analysis had been done with<br />
squamous or small-cell peripheral tumors in the middle or<br />
lower lobes . We were unable to do tl>ese calculations because<br />
only 8 cases fined into this ategory .<br />
Actually, the finding of a possible risk of squamous and<br />
Kmall-eell tumors in the middle or lower lobes was somewhat<br />
unexpected, given that dust particles tend to adhere to the<br />
upper lobes, and tuberculosis usually affects the upper lobcs .<br />
To see whether calcified foci or fibrosis in the upper lobes<br />
could account for the higher RR in the middle or lower lobes<br />
because the previous presence of such lesions might disturb<br />
the expected distribution of inhaled particulate or gaseous<br />
matter, most of the chest radiographs of cases with squamous<br />
and small-cell <strong>lung</strong> tumors were re-txamined . No significant<br />
difference was found in the proportion of positive cases with<br />
upper lobe vs . lower lobc tumors .<br />
In out analysis of all never-smoked cases, the lack of a doseresponse<br />
pattern, and an almost consistent drop in the RR at<br />
the highest doses of <strong>exposure</strong> would seem to lend linle, or<br />
only weak support for the passive smoking linkage with <strong>lung</strong><br />
<strong>cancer</strong> for women in Hong Kong This might be due to the<br />
facr that it has been estimated (Rylander er al ., 1963) that the<br />
non-smoker exposed to environmenul tobacco smoke receives<br />
about 1% of the active smoker's dose of tobacco smoke based<br />
on coatnine levels in the body, and this is toughly equivalent<br />
to the tobacco smoke of 0 .1-1 .0 cigarene inhaled by art active<br />
smoker in a day . Moreover, a 15- to 17-year longitudinal study<br />
of 97 non-smoking females in Holland did not find an usociation<br />
between passive smoking <strong>exposure</strong> and pulrrionary function<br />
decline (Brunckreef er al ., 1985) . Thus the effects of<br />
passive smoking might be so weak that they are easily overshadowed<br />
by other environmental factors such as diet or <strong>exposure</strong><br />
to inhaled gaseous/paniculate rnaner from other sourtrs<br />
in the home or the workplace .<br />
When the <strong>lung</strong> tumors were segregated by histological rype<br />
and location, the resulting analyses showed that peripheral<br />
tumors in the middle or lower lobes, and squamous or smill•<br />
eell tumors in the same lobes, exhibited better RR parurns foi<br />
passive smoking in terms of consistency, strength, arxi dose•<br />
response . We are not sure whether this proclivity for passive .<br />
smoking-relat.od <strong>lung</strong> tumon to reside in the middle or lowei<br />
lobes might be due to the fact that the lower lobes have morc<br />
bronchial cells at risk than the upper lobes, or whether the<br />
size, weight, or composition of gaseous or particulate manet<br />
from passive smoking may favor its adherence to die periph•<br />
eral areas and the lower lobes . Nevertheless, the overall proportion<br />
of <strong>lung</strong> tumors in the middle or lower lobes among oui<br />
88 cases ranged from 27% for the peripheral turnors to 209E<br />
for the squamous or small-cell tumon . Thus, the rrujoriry o .<br />
<strong>lung</strong> <strong>cancer</strong>s among our non-srnoking population were proba~<br />
bly due to some factor(s) which yet remam to be identified,<br />
The results from this uudy, showing a weak effect of passive<br />
amoking on the risk of <strong>lung</strong> <strong>cancer</strong> among never-smoked Hong<br />
Kon~ Chinese women, must be interpreted autiously, since i<br />
was based on only d8 cases and 137 controls . With this umplc<br />
size, RR less than approximately 1 .4 would be difficult u<br />
detect with 95% power and at the 5% level of signiflance<br />
This problem was even greater when the cases were suatifKc<br />
by histological type and location of the primary tumor . How<br />
ever, these data seem consisunt with the findings from othe<br />
epidemiological, biochemical, and physiological audies i•<br />
showing higher risks for squamous-eell eumors in the peripF~ ~<br />
eral areas of the <strong>lung</strong> . Confirm>Uon of these findings fror, ,<br />
other studies is therefore needed . ~<br />
ACKNOWLEDGEMENTS<br />
Cz<br />
We tfunk the Hong Kong Anti-Canoer Society and the Un<br />
versiry of Hong Kong for financial auisunce in the carryin<br />
601<br />
OA<br />
CA<br />
0;1A<br />
C4
MSSIVE SMCW,ING IN CHiHEESE hEMAlES 169<br />
pn of the fieldwork . Wc are also irsdebted to the US Natiorul the dau The ucrcurial usisluKt of Mrs . T. Lun, Ms . A .<br />
Ctncer Institute's Folury lnternatlonal Center for sponsoring Chow and Ms M . Chi, and the graphics work of the MedicaJ<br />
a 4-month Visiting Scientist post in the Epidemiology and lllustration Unit, arc gratefully uknowkdged .<br />
B,tosuds•tics ProYnm, which was invaluable in the ana3ysis of<br />
E+ttsur.' . N .E ., and DAY, N .E ., S+a+inirol rwrihodi iw owcrr rouorrA,<br />
IARC Scimcific Pubbaaia+ 32, IARC, Lyon (1990)<br />
®tu+EUaEEr, B ., Ftsn+Ex, P ., REwur., B ., Va . pEa Lcxt[ . R ., Sewou<br />
TEt., 1 ., and Qu .wEa, P ., indoor aur pollution .nd iu cf(cn on pulrtarurr<br />
}ynetion of arJult aon-smokinS women ID Pissive vrolun3 md Pulmosnt)<br />
funcYionJa J . Epidem , 14, 227-230 (1925)<br />
RFFE1tENC'ES<br />
QuN, W.C ., and Furw, S .C„ L+mI anccr m .on•smokcn io Honl<br />
Kanl M, E Grundnw+n (ed,) . Cancer camperjn, Vol 6, Canc-rr eplde•<br />
a:olol(y, pP . 199•202, G Fuchcr, SaraSsn, Neu York (1912)<br />
Coa>tit, R ., Retem~on of ciprette<br />
croke eomponenu in twnun IunYs Arch en,iron Nlrh„ 11, 746-748<br />
l t9d8 )<br />
Fu¢+.+A,w, G .D ., PtTTm, DB . . and B .WoL , R .D . Prcvdcncc .nd Cor•<br />
teLtex of ptuive smokme Amer . J publ. N6h , 73, 401 405 (1983)<br />
6ARnwrJ .u, L ., Time uends in lunj <strong>cancer</strong> mortality .rtwnf t+onsmoken<br />
snd b nae on pusivc trtwkine I fta Cnncrr lur , 46, I061 • 1066 (1981)<br />
GAitstractl ., L ., Atrouux, 0 . . and 1otnEaT• L ., Involunury imok nI<br />
and )un3 eancer ; a case-control swdy . J . Pat Cancer lnrr ., 75, 4b3-469<br />
(1915),<br />
Htc.tY .MA., T., Non-smo)un8 Wfvea of heavy srnoken have !a hiElxr risk<br />
d lunj wtcer : i stud) from Jqun . Srtt, rnrd J., 2i.2, 1S3•1t5 (1961)<br />
k,uAT, G .C., and r/YrmER, E .L. . La.= arcer m wn-unokers<br />
Cancer, 53 . 1214-1221 (198A) .<br />
K .+trrx, A . . BoH,, H and SewHrr~r, F . • Pusrvnucfien .IS LunFcnkrebs•<br />
~esr~che bei Nschu~..uchennaen . Yed . k6n . Pra: ., 71, 5a-59 (1983),<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Koo, L,C ., Ho, J,H-C ., and L[E• N ., As aealysis of wme risk faaon<br />
for Luas <strong>cancer</strong> in Honj Kong hv . J Cencn, 35, 149-135 (19t5)<br />
Koo . L .C . . Ho . 1 .H-C ., and S ..., D ., Acvvc ard pusive tmokin; aman4<br />
krrxle bns <strong>cancer</strong> p .tienu and eorttrots u Hon= KonS JI cyeLn<br />
Caurr Ret ., 4, 367•375 (19i3) .<br />
Koo, L.C ., Ho, J .H-C ., and SAM, D ., l+ pusive mtoicinl an aided risk<br />
L.ctor (or km3 amr in C'htnae rvoeten'' J. eq . du C.nc,rr Ret., 3,<br />
2T7•213 (1994)<br />
Lua+w,1 .H , A eomputer for the an.lysis of smclsed ere ooaad<br />
rtudtes ud t e s Consp d,a+ned s ., 41, 13i•143 (19Y1),<br />
Mn.t.Ea, G .H ., Cancer,pu sive smokin~ md .oa«nployw aad emp(oyed,<br />
wt .cs Wrn . J Aled, 110, 632d35 (1914) .<br />
RYUwoc. . R ., trrusor. . Y ., and Srr¢uJ. . M{•, (c'd ) . E7S-EnNron•<br />
•.erua! uboecn rwsote Atar, C•~ersev . (1963),<br />
S1,HOtEK . D,P ., Wucoz, AJ ., and Evt3ao«i, R .E ., Cumulative effecu<br />
of lifeume pauive anokJn3 on nrtcar risk Lancet, 1, 312-315 (19E5) .<br />
SToN[ . D .1 . GLucK, M C ., and PAucH . N .K„ Pranical Poirus in pu(twonan<br />
diuaut, p 125, Modsca) E . .rnv~•iio„ Publss<strong>lung</strong> CDntpany, New<br />
York (1976)<br />
TIwE, ArJa of rAe body, p 59, Rand MeNally . Chicaj*o (1950) .<br />
T>ucHOrout.os, D ., KALAHwot . A ., Sn.nRos, L., and M.cMk»ou, D .,<br />
Lun3 aricer vid pISsIK un0(C]ng Mr. J. C.ncrr, 27, 1 .4 (1911) ,<br />
Wu, A .H, HermEnsoti, B E ., tucE, M C ., and Yu, M .C ., SmorinS ard<br />
ot)ter nsk (.non for Ja+u euKSr in woarn . J . wt. C..ncrr htrr„ 74, 747-<br />
751 (19fI5) .<br />
Wrwnuc, E .L ., and GoooMAn, 1.t T ., SrtsoklnE and lun; nnaeT~ aotne<br />
anreaolved i .sues Ep,drm .. P" ., ; . 17';-207 (1983) ,
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
9
Lee, P .N ., Chamberlain, J ., and Alderson, M .R ., "Relationship of<br />
Passive Smoking to Risk of Lung Cancer and Other Smoki .ng-Associated<br />
Diseases," British Journal of Cancer 54 : 97-105, 1986 .<br />
<strong>exposure</strong> in the workplace and nonsmoker <strong>lung</strong> <strong>cancer</strong> was published in 1986<br />
Another European study including an assessment of ETS<br />
. The authors wrote that "overall the results showed no<br />
evidence of an effect of passive smoking on <strong>lung</strong> <strong>cancer</strong> incidence<br />
among lifelong nonsmokers," although they presented no odds ratios<br />
for workplace <strong>exposure</strong> . The following point estimates have been<br />
presented by one of the authors of this study in a recent book :<br />
for females, 0 .63 (95% CI 0 .17-2 .33) and for males, 1 .61 (95o CI<br />
0 .39-6 .60) .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
;.~.;,,. . .. _ . . _ _<br />
it, J C,,,rr. (t y0) . ,bl, }7'!OS<br />
Relationship of passive smoking to risk of iung <strong>cancer</strong> and<br />
other smoking-associated diseases<br />
P .N . Lrt,` J• Chambrrlain & M .R . Aldersonf<br />
bssrrrHrr oj Csncrr RcuorcA, Chjton Road. icG*o++r . Surrsy . UK .<br />
S. .ry la t*e lasrr r+an of a(arjc kcnr .ul ps>< .oontrol ∎udy .f al1C #ciuYCnship of trl+c of aastctu<br />
rnoked so nYi 01 v.noux sewol nj•assavtod d-sc2ses . patoents an+ .rrv6 tiuca+wnt rsn tk .molsnj kaF∎tt ut<br />
tJanr first ly+o..e and on shc sannt of pysure s+nokt tayosun at Ao+ne . at rork . slunnY sravsl an.d dunnp<br />
kcwrc In an e:tenuon ef t!w uudy an .ttempt vu a,ade to oburn raokt+nj Aab .t dau Euutlr trorn the<br />
apouses ot all Mfebnt non•tmokint <strong>lung</strong> onocr wa and ol tvo Netonf Ron-smoktnl matehed eaatrols for<br />
uch auc The attempi .ac nudc reprdles of .scthcr the ptienu iad ansrcrad p .u++c trnolurg rirauaru<br />
iws hosput or .ot<br />
At•aonpt tifetonj ao*-uno4M . pan+K sn+oking .a3 aot anoclatad .'nh an7 trMrxiat i11c1WG tn ntit o(<br />
kmt arssr, ehronrc bror,chuu, atclucmrc hcan duux or urotc rn any analrus<br />
L+miutiom o( put suud,-s on pass~" smoltnt arc dunusad and t!x a .ed for (utther ea~earsh rr+dcrttncd<br />
Fron+ all the ar.,Lb1e r+denax . tt appc.in that any efT.n of dan, .e arnote on <strong>ets</strong>l o( any of th¢ asa)or<br />
9ueara that 1as bocn asu%vtod with an~-c amoAtnZ u at sncst smalL and au> >+ot sa .u at aJl<br />
Srudy ojAospire/ n-portrnts<br />
In 1977 a largc hospital easecontro! .vas initiated<br />
to study the rctattoruhtp of the type of taprstu<br />
smoked to ruk or lun ; eanaet• ehrontc bronehitss,<br />
ischaemic hean disease and strokc This sttxiy was<br />
orried out in IO hospital rt :rrons in E.ngland ;<br />
intcrvretitn4 tnded in lanuary 19112 , The ongtnai<br />
qurst+onnatrc did not includc questions on paisive<br />
fmolcinj as tt -as "t considcrrd an unpontant<br />
Itsue in 1977 . However, in 1979 it was de+nded to<br />
txtend Ihe questronnaire lo eovrr paut+•c smoktnj<br />
for rrurned patrcnu for lhc tast four ricrons to<br />
begin intervmnng Subsequent(y, in 1961, follown4<br />
publtcation o( the papen by Htrayama (19E1) and<br />
by Trichopoulos er o1. (1911) elatmtn j, tha t nonsmoking<br />
wt .ts of tmokers had a s+jnifieantty<br />
greater risk of <strong>lung</strong> rancsr than non-srnoktng .wes<br />
of non-smokert, it .as dectded to iiricreau the<br />
dumbcr of inacrvirws of numed <strong>lung</strong> anoer nses<br />
and eontrolt The ectended qtxsuonnrtre was then<br />
administersd to ahex patienu in all hospttats rhere<br />
iatcrncwtnj wI.s uill conunutnj<br />
lydllo+r-srp stsdt• O/spustl s/rtrsrs-t+r+rs[+R{ Aatpiral<br />
aii-prsrnu<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
(n t9t2. sfter intervieWing of Aospiul in-p.tieats<br />
had barn eompletod . it was dmdcd to prry out a<br />
fo1loW .up atudr . !n this uudy . an attcmpt taas<br />
Cornt{wn,der,tt, P .N tac<br />
7roeat lyddnas 25 Goar Aaa4 Swsoe, S .arrty . SsA .?<br />
f1yG .<br />
tM4nsene addr .a Olfiae rif !•oqulauoa Censsaast .nd<br />
Zur.ers. ft Cat4r.c's Hot.e . lo Kiapway . LowQon<br />
w1:2{ slp .<br />
snade to intrrview the spouscs of all of the numcd<br />
hospital ip-pauents with <strong>lung</strong> t.unaer who rcported<br />
ftrer hivtnt smoked . as well as of two marricd<br />
non .smokinj controls for och of thcsc indc>< <strong>lung</strong><br />
ancer ases The foliow•up study wYs intended<br />
paniy to sompare inforrnatron on spousa' smoking<br />
kubits obtaincd fsrst•inartd with that oblaimxf<br />
axond•hsnd dunnd ahc in-gutirnt intcrivicws . and<br />
partly to ssbtain somc dnta on aq .ours' amoktnL<br />
ksbu for thosc pa .cnu who had wot anac.Krcd<br />
pauivc smoking quations u+ Isospttat .<br />
This papcr ennocrttracts aolcly on the iuuc or<br />
prsuvt smoking in litelong non•smokeri Giaults<br />
relating to typc o1 dgarrttc smoked arc deuritscd<br />
ehewhert (Alderson rr a1 ., t9iS) . whtbe a cletaikd<br />
+rport, arailabk on "uest from PN(., eonsiders<br />
Ux orsrall findtnrs from thu sueronarol uudy .<br />
!r1 rtt,otEs a r1 rts'ewt<br />
Stwly of hosritot aa-ratirarts<br />
For act, of lhc 4 is+dca diagr>oazs (lun& canc .ohronlc<br />
t•ronchitis, iachat:mtc inn diseasc ar_<br />
strolc), the intsation was to inurview a00 casrs<br />
usd 200 ntsatrhod controls in tach oC tbe Rtrht<br />
aat/age mlls (i .c . mak o( kmak. tusd aged ]~<br />
45-~4, SS-64 or iT-74), 'fhis ;ave a tarret of<br />
12.t00 petxnts, though fs» sone atcfonss te .U<br />
young femak ehronst Woncftitses) this rrould be<br />
tuutuinabk . huenu werrc wiactsd from aredksl<br />
(tsdudioj ch:st taedsdine). Usorseic turrcry, and<br />
tadiotAcrapy .ards . Conuoh Wene paticnu without<br />
•ese of iht four i+rdcx diagnaaes, iadivsdually<br />
toatcfisd b seses oe tca, a,fe ., boxti;Htal neYion ar.d,<br />
0 71c /s4,c,nittan h:oa t.td , 1"6<br />
I
1st f N LE F a .r<br />
when possibk, hospital ward and tsme of sntrrr»cw .<br />
SuMtpu•.ntly, whcn final discharge dtaFnoscs<br />
txs.arrx avatlahk . thcy were used to rcalloute asts<br />
and controls as s+eersvry Patients without a finxl<br />
diagncx_is keT+t thcir (xovrstonal draFnosts Where<br />
chanEcs m casctontrol sratus oaurrrd, paticnts<br />
were rcgroufrd intn nrw osetontrol pairs as<br />
appropriate With the asststancr of Sir Rschard<br />
Doll s+r,d Mr Rw•h,,rd Petu, non-tndcs duEnoses<br />
werc classtficd as follows<br />
ciass tA 'definitely not smoking associated'<br />
clau 18 'probably not smoking associated'<br />
class 2A 'prob+bly smoking assoaated'<br />
class 2B 'dcfnttely smoking assactsted'<br />
Controls with no final diaFnosts were considered<br />
class tB Ovcrall, thcrc were 12,693 intcrviews<br />
carried out which srsulted in 4 .950 pairs with class<br />
I controls and 73P patrs with class 2 controls .<br />
Ttyer : wcrc 3 .g3 : interviews of marrtcd cases and<br />
controls whcrc the passive smoking qucstionnaire<br />
was completed In order to avoid substantial bu of<br />
data, duc to one mcmbcr of a pair rsot being<br />
marrscd or not compkttnE thc pauivc smoking<br />
qucstionnairr„ it .as decidcd to ignore matching<br />
when anatysinj thc pauire smoking data and to<br />
comparc cach rndca sroup with the combir>ed<br />
controls Numhcrs by acs and asccontrol status<br />
•re riven in Tablc 1 .<br />
Tab1e I Numhers c/ msrmd twspital in-patsents<br />
ownt+tct nt p.u,ve amol:mj rJuesttonaatrn<br />
Mat. fe.rk Ta+at<br />
Lunt canat $47 245 792<br />
t'hronK broechttu 182 N 266<br />
(sehaemK Mean dtsease 216 221 !0'f<br />
Stroke 161 137 2!1<br />
Contvok<br />
Clas, tA and 1!1' 8)9 713 1J52<br />
Lhasr. 2A and 2!S` 2" 149 417<br />
Total 2.213 1549 U32<br />
'Othcr dnc.asos .rtrs dauift.d by dclFnc a( asokins<br />
wocutrcro - dass IA rkfiatsety wot, dass 1t MobOWy<br />
tol, das 2A prohably, dan 2! 6cfrrutely<br />
In the pass+vc amo .rns prrt ol the questionnaire,<br />
patients wrn: asked whcn the aurrute siart .d, if<br />
and when it had andod ; the lumber of<br />
osanufactured ciprtttes per day smoked by the<br />
spuuse both during the last 12 months of aurtia`e<br />
asud also at the period of maaimum smoking during<br />
the nlamaje, and whether the spouse oMer ttYutarly<br />
smoked hand-rolled eiprettes, dprs Gr a pipe<br />
during the marriatc For amnnd or subsGquent<br />
tsarruga, queuwru related to the Gru anarria=c to<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
give the IonEcst taunt snterval bctwecn <strong>exposure</strong><br />
and dtseasc onset The S+attcnu wert also asked to<br />
quanttfy, acxord+ng to a four•potnt acak > ;a lot,<br />
average . a kttk, not at all), the extent to which they<br />
were reEularly esposed to tobacco smoke from<br />
othcr rcoplc fxior to comtnF tnto hospital in 4<br />
ssituations at horne, at work ; dunng daily travel,<br />
dunng ktsure tisrse, In the main qsses .tionnain,<br />
dutaik-d qucsttons wcrc askcd on smoking habits<br />
and on a whole ranFe of possibk confoundtng<br />
variabbes<br />
Follo .-srr Nsd) of Jpousas of raon-smoli+sX looaptrel<br />
An-patwnts<br />
From the hospital study thcre were 56 <strong>lung</strong> tan=r<br />
qws who reponcd being hfclong non-smotien,<br />
who werc marncd at the time of intervier and who<br />
were not known to have bccn married previously<br />
In a follov.•up to the main study, an attempt was<br />
made to intcrvxw the spouses of thcse $b cases and<br />
also ihe spouses of two hfe-lont non-smokine<br />
controls for tach ase, indtviduxlly matched for ses,<br />
tvuntal status and 10-ycar arc group and, as far as<br />
possibl ., hospital Where multtpk potential cAntrols<br />
in the same hospital wcrt available, thoac<br />
intervicwcd warest in time to the case were<br />
selected Whcre suitablc controls in the samc<br />
hospital were not a~ailabk, thoss in the nearest<br />
Isosptul werc ehoun<br />
because names and addresses of the patients were<br />
ssot recorded in the hospital study, st was neacssar)<br />
to to back to the hosp,tal both to obtain this<br />
information arid also to get pcrmtsston to intervxu<br />
their spouses FollowinS some nefusaVs both by the<br />
iwsprtal and by the tpousrs . sucrosful intervsews<br />
were obtatrsed from spouses of 3 ; cases (10 wives<br />
and 24 husbands) and 90 controls (26 wives and 5A<br />
Musbands) whosc condition was definitely or<br />
probably not related to smoking<br />
Intcrvsewinf was carried out between July 19$2<br />
and August 1913 The spouses were asked about<br />
their eonsumrtson of manufactured cigarettes,<br />
t:iFars and pif+cs (a) rsowadays, (b) dunng the year<br />
of admrssion of the patient or (c) maximum durinf<br />
the whok of the rnarrsagc The spouses wKrs oot<br />
asked about the smoktng hatwts of the i+rdes<br />
prtsent The sf+ouus wne also ∎sked questiont on<br />
sEe, oerufutson, aoetal elass and a range or othcr<br />
potential confounding factors .<br />
Starisrirol awraAods<br />
The statistical methods ars kused on eiassiesl<br />
proocdures (or analysis ot Srouped data derived<br />
frorn nse-eontrol studies (Breslow & Day, 1980)<br />
In Senenl, the material Aat been etumincd as a<br />
2 x K x S tubk, with A' rcj+rescnting the levels of the
isk factoc of Interast and S the rsumbcr of ttrata<br />
uscd to takc axount of fsotcntral confoundcrs<br />
Results ptcxntcd arc for the combined strata and<br />
sho~ the rclatu .c nsl. (Manrcl-Harnszel esumate)<br />
to=ethcr with the siFntf~canac of its drfTcrence from<br />
a basc kvel (nil 1 0), and or the dnsc-rclatcd trend<br />
In analyses ~of the data cnliectcd in fsot(ntal,<br />
comransons arc made hctMccn oscs wtth e<br />
panicular indcx dncasc and all the controls with<br />
drsoscs dcCsnrtc(y or probably nnt related to<br />
smoktnp Srs umpic indrocs o( pas%ive smokc<br />
e>trr nses<br />
and 112 matched controls rho refsoned nrver<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
M^,~ •Y+` .Mw<br />
tASSIYI: iNOKING AND ssdoKtNC-..RL( .ATCr) niSFASfS a,<br />
having smokcd in thcir hosryrtal intcrview Of tlvcsc,<br />
therc ercrc 47 casa (IS mak and 32 (cmalc) and %<br />
controls (30 rnak and 66 (cm.k) for a+,,om sortx<br />
information on srnokrnF habits of thesr srnuscs was<br />
availabk Of those 14] pausnts, information on<br />
"usc smnktnE was availahlc hcsth from the slxsusc<br />
and from the paticnt for 59 (41•h), from the s(soucc<br />
only for 55 ( .1lS! ;) and from the patrcnt onl) fur 29<br />
(20%) Table 11 slwws Ihc estrrnatcd apc•ad)usrcd<br />
retativc nsk of <strong>lung</strong> nncer in relation to a{xw%c<br />
smoking durint the vshok of tlu marnaFc, by act,<br />
source of dau, and f+enod of smokinF None of the<br />
9 relative risks shown in the uhk are statr%trcalls<br />
si¢nifrnnt, Whtn daln for hK+th seses and both<br />
sources arc twnudcred, thc rurmatcd ro(rtrvc nsks<br />
in relatton to spousc arnokrnF arc closr tn I(1 .11)<br />
For individual Caa or fouracs, whLtc numhcn of<br />
saxs and controls arc amalkr, rclauve risks vary<br />
morc from rmity, but sa consistcnt pattern is<br />
tvident S+milar oonclusions wrn rcached . when<br />
analyses wsrc based on smoking durinb the pcar of<br />
kaapital intcrview Herc, the overall n :latrvc risk<br />
was again cbsc to 1(0 93 with limits 0 41-2A9)<br />
Tabk III wmrnariscs concordancc bctwcen<br />
spousc's rrunufacturod agamtc smokrnR habits as<br />
rcponed directly and indirectly for the 59 (,atrents<br />
with dau from both sourcrs b,scrc7wncres were<br />
uen for 9 sfsouscs (IS! :) in rrsfsect or smnkrnF at<br />
sAmc time durin ; crsarruFc and in the rrsc of 2<br />
T .We 11 Rttsru+n .hir bnacn apovst'r wunufactur.d o[3t0S0-)4r1<br />
L+rl .e wur .rx.-s .J rAr nlri Iwww n bsrud (M pusnu+)<br />
Mak 7 IS 5 7 133(0 17-6 -Lt)<br />
Femak 9 17 1 70 6 7510 24 .2 40l<br />
Camb+ned It 32 1) 21 IQCNOEI-2<br />
Iastl .r, /utr awncn .f q/ar>warba . (!I) p.rrerwsl"<br />
Nak 7 It. i M IJO(O .LCJ .rI<br />
Ftrnak t0 21 22 45 IAOt0 .)1-2T1)<br />
Combn.ed 17 37 - 30 !1 1 .1110,51-2 .1'91<br />
"Jwty owstras twcsud .d rn (otb. .,lp .rdi tuaoecnd, %ta ttws a.atysu urc<br />
apousr .as aounted as a rnoker if repon .d to Ic ao atLer dlr.csty, y thc tposrse<br />
Iurinl (ollo .-up batcrvie., t,r, :drr.esty, by the palient ia Aogital Nae tlut tAe<br />
S1 ptrcn9s bt wbom iators .asion . . sposrc arnokin5 ..as availabk Ilrtna boah<br />
srwren are mduded in all ) aaalyser.
s .n rN t_rrr, .r<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
T.Mr III Cnnnxdancc hrt .rrcn stu+u :'t manulactvrcd a}arctt< sw+nttnE latrts as rcpivirted<br />
itracyll and Md,r .nly<br />
S. : ./ps,~ru/ra.sr nwrr .f rrtu<br />
Ma4 fn .dr<br />
Ctsn C.wr .ti Ca.rs C .wwr .ls Ti.e!<br />
St+ousr a sm.+kn scxnctmx rn<br />
lnarrutr Itlt'++dutl H+<br />
iubject and srovu 2 6 S 13 26<br />
Only wh)eO I 0 0 3 4<br />
Only spousc I 1 3 0 S<br />
Nathcr 3 It 1 1 24<br />
; sub)ect!spousc aFrerment 71% ttt% b7;, tt;, t5'i;<br />
Spouse a snrolrr during ycar or<br />
htrsp,ial tntcrru+ ao:ordtns to<br />
Luhjco and spouse I 6 2 4 1 3<br />
Only subjcct 0 0 O 1 !<br />
Only $tx+usc 1 0 O 0 1<br />
I+o .thc, S ty 7 ~<br />
% suhXct/sPa+sc aErecmcnt {t' ; t
s<br />
a<br />
a<br />
M.SSIVE SMOKING ANll SMUKING•Rf.L1.TF.D DISr.ASES Ht<br />
T .Mr It' i.ctalrc+nshrn -t .ocn .ar.ovs awdwn of p.ut .t .nu+le cal~'+.uK and ndl of Irn1 unon amonR kkloar wnn•<br />
.m,•lrrs luandardi .c .f k,r as< and, lot t{.ourc ur+ollnL .IsctYsci sAt ssurrurr .a . onpwnt 04 ewdall<br />
-<br />
Iasslrr .wnlr F(alr wvats ie .a.lr prwus S+an rr .sMwd<br />
e :p,surr - -<br />
rslrc/1r+r! C." C."rrr4r<br />
r<br />
R C .v, Cw-+rnlr R CRVS Crwrrsls R<br />
At Iwmc<br />
Not at all • 101 1 21 112 1 3+0 293 1<br />
Ltttk 2 21 122 6 0 092 1 66 0"<br />
AseraEva lot 1 I I 1 I I 5 61 0t1 • 72 Olk+<br />
At wotl<br />
Not at ail 3 410 I 12 113 1 IS 151 1<br />
Ls,tk 6 29 3 .24 3 21h 1 I% 9 55 112<br />
Avcral:c'a lot 1 29 0466 0 t1 00 I a7 019<br />
. Dunn f travcl<br />
Not at all 1 101 1 211 2 31t 1 36 3" 1<br />
Ltttk 3 16 206 2 SI 033 5 61 06A<br />
ArcraFe'a lot 0 13 000 0 13 000 0 26 0 00<br />
T rrnd<br />
jt+etatl .cl<br />
Ic005<br />
:<br />
.<br />
f<br />
Dunn1 klsvrc<br />
Not at all 3 45 1 15 116 1 13 161 1<br />
Urtk<br />
AverrFc'& tot<br />
4<br />
5<br />
16<br />
3'"<br />
1 12<br />
3 16<br />
11<br />
2<br />
107<br />
95<br />
1 05<br />
01!<br />
Trcnd<br />
11<br />
7<br />
155<br />
134<br />
1 .06<br />
059<br />
CombinC4 /r1de1•<br />
~<br />
IKK1lIK)<br />
I',: 005<br />
Scorc 0-1 1 2~ 1 10 .?5 1 11 102 1<br />
Scors 2-J 7 35 13,4 S 61 063 12 116 lDd I<br />
fcors S-12 2 IS 320 0 21 0D0 2 36 050<br />
S(+ousc tmoled man ofs In Last 12 months<br />
No 10 105 1 20 19? 1 30 2.91 1<br />
Ya 2 2'9 0 % 11 122 076 13 151 079<br />
Spoust smoktd man oEs in rhok or atnaSc<br />
No 7 93 1 13 119 1 20 182 1<br />
Yn S 40 2 47 19 229 055 24 ?69 690<br />
•tuod on wm ol 0- wo1 at all . I . 4ttk . 2- asraEc . 3- a Iw tot at MOmc, at fMk, duruME 1prcl, durmE knuK<br />
asc"113-ice<br />
Over thc prst 1yurs thcrc has becn considcrablc<br />
rsuarch interest in the relattonship belwecn passive<br />
trnolrnF and risk of IunF eaneer in nonsmoken<br />
Whiic some studres havic elaimed a positlvY efktt<br />
(Hlrayama, 1991, 7nchohcwlos rr al ., 1911 . Cornci<br />
rr al„ 19R Garfinkel rr $l ., 1995, Giths rr .1. .<br />
1994 . Knoth trr •!, 19t1), othen (Suftkr rr sl . .<br />
1994 . Chan, 1982 . Garfinkel, 1951 ; Kabit and<br />
Wymdcr, 19it1, Koo rr a1, . 191r) kavc found tw<br />
tiFmft::n; risks of WnE<br />
nncer for nors-anokinE women srumed to vnokers<br />
wmparod to non-sawkinE .+omen Rsarried to aon•<br />
tmokers nnFe from wnurvhat over 2 in the<br />
1'r.chopoulos and Cortca studies to around O .')S in<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
the burTlcr and Chan studies 7}u WeiEhte4 relative<br />
risk from theu Nudlcs ka bccn cstlmatad by us as<br />
approumalely 1 .3 . Whik there is, therefore, a<br />
t
la: r.N t.rrr+a+<br />
yak~k V KCWuMl111p hctWt'tli 1wo MdKD or Ifaf .uK fTnIt c1rOSYTt and ntl 01 C:htOnK (KfNKhllt3, aKhit1711c •pn<br />
Ancarc and urolt amc+nE IJctont pon•snwlcn (atundardiw7 tot aFr and . tot is{oust tmokant. rAtllw tbc Irurrurc wat<br />
6ntnlnt ot srdadt<br />
raaurY sr-1r Mak'Irwlu3 le.rsJr rar.wti ,ftatt cwdwwel<br />
ti)W,arr<br />
./ .dri/lrlrl Ca.n C.rurrJi R Casn C.•urnlt R Caut C .+rrds R<br />
C/rnw/r IrwwrM'lit<br />
Cornbinal u4ct'<br />
Scott 0-I I 27 1 7 73 1 1 10Z 1<br />
Scorc 2-4 2 55 013 4 61 I05 6 116 100<br />
S,corc 5- 12 1 IS 110 1 21 1 .03 2 36 I10<br />
Sl+ousc unolal man cip rn .hok ol marnalrs<br />
No a 93 I 4 99 I 12 I{2 1<br />
Yes 1 -60 0.3+ 13 229 1 .22 ta 269 0.13<br />
LrAo~u lwan dvuv<br />
ComDbncd InJci'<br />
Scorc0- 1 15 21 1 2) 75 1 38 102 1<br />
5cort 2-4 12 55 01) 9 11 059 21 116 0.52<br />
Storc 5- 12 3 IS 04) A 21 Olll 7 36 0.61<br />
S(+Ouu smnlcd man np tn . hnk o( mamaFc<br />
Nu 26 93 1 22 19 1 4E 1t : I<br />
Yts 15 40 1 .24 55 229 093 70 269 1 .03<br />
S+rol r<br />
Comb"ncd rnSca•<br />
Scott 4 1 5 27 I 19 75 1 24 102 1<br />
Scott 2-4 10 15 f0 LI 096 20 116 091<br />
fcorc 5-12 ~ IS 177 7 21 2 W 11 36 2.11<br />
Spourt smoled man op In .Ac.h od marru~c<br />
No It 93 I ' 19 19 1 31 1t2 1<br />
Yes 1 40 0u 19 229 092 55 269 090<br />
'Oared on wm o/ 0- not al all, 1 . 4nk, 2- avsratc, )o a tot for at Aomc, at .or1, aunnt trartt, Iurnis kxsurc<br />
onc eapretlc would be 1I hours as tsEards<br />
panicuhlc mattct and SO hours as rctards nicotine .<br />
S+milarly, larvis et .1. (1965) havc Mown that the<br />
incrcasc in sahvary cotlninc in rctation so passive<br />
smoke cxfwsurc is kis than I'.4 of that in relation<br />
to activc amokc caf+osurc E :trapokatint hncarly<br />
from the t0-fold tclalwr rssk of king nncrr in<br />
lclalion to scllvc unoklnf would thcreforc predlct a<br />
cclative risk in rNation to rassive smoking kn than<br />
1 .1, while a quadratrc catrapotation, as tujlccted<br />
by Doll and Pcio (1979) would predict a lower risk<br />
aill . The contllct bctwrcn Ihc dou and the claimed<br />
raponse ia panicularly dear for the tasults ot<br />
Hirsyama (I"l) who found a aimitar efiact on<br />
lunj txncer ror passive anoking as fbr active<br />
smoking ot S ciprttla a day .<br />
5ccond, all the audia wffer from weak caposure<br />
data, most studia only obuinin3 infortnation on<br />
the tpowe's smoking habits and aonc obtaining<br />
obIoctivc data by measurement of ambicrlt Ilcveb of<br />
tnwkc oonstituents in thc air of the 6otrse or<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
workplacr anG/or of concentrations of constituents<br />
in body rluids .<br />
Third, ao Nudrcs adcquately uke into account<br />
the possibility that misclassification of activc<br />
smokers as non•txnokers may 6avs oonsiuently<br />
biascd relative mk estimates ",ard Activl :<br />
amokcn havc a lugh rslative nisk of king ancrr<br />
and apouscs' smoking kabits are positively<br />
Oorretate•d fecausc of this, t1 can 6e shown tbat if a<br />
tclalively tmall prof+ortion of arnoken reny<br />
amokinE, this resuhs in an aploreal c"tion in<br />
risk of IunE pnar in 'aon•smokcri tnarricd lo<br />
amoken compared to ' .on•atwkm' nsarriad to<br />
aan-smokcrs, even when .o rsar sffon of pasaive<br />
smoking caists A dcmonuration that this aouroc or<br />
Was is of rcal Imporuncc can be found in the study<br />
of Garfinkel tt .! . (1985) Used on ttrlvalidated<br />
smoking data takcn from hospilal taoles, a rolative<br />
risk of lun3 nncxr in relation so Musb .nd's<br />
smoking at (some of 1 .06 was pkulated, with<br />
t'eiativc risks of at kast 13 aecn irs rclation to each<br />
:='-I<br />
_. . .. . . .~.,.~ ... .,~ . -....
t<br />
k<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
kvcl or husband's oEarcttc smoking and in setation<br />
to huaharsd's ctFar and pipe smoktnt When<br />
addittonal sourvs of information on atnoking<br />
habtts were used . the overall rnlattvc risk was<br />
rc,duced to a marpnilly ugnif"nt 1-31 with an<br />
ekvatec3 risk onl) n:a1t) dtsrcrniblc in rcl:tion to<br />
fteavy cilare{sc smoktnE by thc husband Evcn itctt,<br />
it is sxwubk that the ckvauon in risk was t .ol<br />
evsdcnt when smoktng data were obtained from the<br />
subject or her spouse directly, but was only evidcnt<br />
when thc data werc obtatned from the dauShtrr or<br />
son or another informant, ir from those pcoplc<br />
who were icst Mkcll to have known the full<br />
amoktnF htstor) The (owcr rrtattvc risk may still<br />
have arisen wholl) or fsarsl) as a bas rt:suliinj<br />
from misctauiftcatton of smokrng habtts<br />
Founh, many of the studies are otxn to tp,xifsc<br />
eriticisms For elamptc . thc aonclus on of Gi11ts et<br />
•1 (1981) that male IunF <strong>cancer</strong> d~caths in aantmokers<br />
rose from 4 per 10 .000 in those not<br />
exposrd to pass vc smoke to 13 per 10,000 in those<br />
who wcrti esposcd was based on a toul of only b(!)<br />
deaths and was not tutisticali) silnificant . Also the<br />
claim by Knoth .r ./ (1983) of a tetationship<br />
between passive smoktnr and <strong>lung</strong> <strong>cancer</strong> in s>ton•<br />
unokint women was based simply oet the<br />
obscrvauon that the proportion of fcmak atontmokin=<br />
<strong>lung</strong> <strong>cancer</strong> patients ltvinE toFelher with a<br />
smoker escooded the proponion o( mak amoke :n as<br />
rcT+oned in the prcvtous microeensus . ignoring inrrr<br />
a4o lhc fact that in man) familics womcn I .ve with<br />
more than just their husbands<br />
In the preunt uudy no tiFnificant relationshir of<br />
passivc smoking to <strong>lung</strong> canccr incrdcnct in lifelonj<br />
t+on•smokcn was seen, either in the arsalyses based<br />
on the information collected in hospital or in<br />
sstbsequent inquiry of the "usn ot both It must<br />
be pointed out, Ao .ever, that the number of <strong>lung</strong><br />
<strong>cancer</strong> pattcnu who had ncver smoked was rather<br />
small so that, though our findings are coasisacnt<br />
with p .uivc smoking hsvinE no effcet am lunS<br />
<strong>cancer</strong> risk at all, they do wot eadudc the<br />
poss;bility of a small incrcase in risk, tlsou=h the<br />
upper 955, sonfidena limit of 1 .50 for the awimate<br />
of 040 (Table IV) in relation to the .pousc<br />
smoking during the whole of thc marriage is nsot<br />
tonsistent with some of the brFer incraaw claimed<br />
by Hiraysma (19i1, 19N) Tric)wfroukoc tr d .<br />
(t9E1, 119113) and Correa rr al (I9d3) .<br />
Thoujh the numbcr of lunI catscer patients who<br />
lud rtevcr smoked a vrull, varying arowsd )4-50<br />
dcpendint on the analysis, this ntxrsbcr ic aot vsry<br />
different from that reported in a stm+ber ar other<br />
ttudies, e .E the fsndmfs of Corrta er atl . (19t3)<br />
.rere based on only 30, while thou of Triclsopoulos<br />
tt d. (1911) . even when apdated (Triclsoyoulot t/<br />
a) .. I"1) srrc haed on only 77 . The difl1ruhy of<br />
obcaininj an adequate sample aix ie ..deriirsed<br />
.. .~.,.w. .s- , .,. ~.~ ------`-- .-<br />
rASSIVE SMOKING AND SMOKtNCrRtilJ17U) DIIUSLS N3<br />
when onc oowdcn that in our study the 44 acver<br />
arnoktng <strong>lung</strong> <strong>cancer</strong> paticnts who comrleted<br />
pauix smoking questionnairss in hospital were<br />
estracted from a tota( of 792 <strong>lung</strong> <strong>cancer</strong> patients<br />
It would srood a very Mrgc research efiori to<br />
irscroasr pracision aubsuntially, and even then onc<br />
would havc to take care that thc masnttudc of any<br />
biasa did aot csaeod the malnitudc of the effcct<br />
one was looktnr for .<br />
The two srulor prosfroctive ctudia which Rave<br />
so far reportod findtnFs on lussive amokin ;<br />
(Htrsyama, 1%1, t'iarfinkel, 19b1)' wero "t<br />
actually daiEncd to investiEatc this issue and, as a<br />
result, could only usc srousc's smoking as an tndct<br />
of eat+osure Out study, on the other hand, thouSh<br />
.ot abk to monitor eaposure objrcttvely, as would<br />
luve been prsferabk, was able to look at pauivs<br />
tmoktnj in a wider context, by asking about the<br />
extent of uposurs at home, at work, during travel<br />
arsd at kisun Although thc answers to tt•.ese<br />
questions were wbjoctivc, and could have eshibitad<br />
aome bias, their inclusion ptrFups allows `reater<br />
oonfidenoe in the oostclusions .<br />
It was interestint that, of the 59 patients for<br />
whom sqwusc's titarrttc smoking habits were<br />
obtained from both the sf+auu and the ptients,<br />
there were 9(IS!k) (satients for whom thcrc was<br />
dtsafr¢ement as to whether Ihc spouse had been a<br />
tanoker at torrse time during thc marrsafc . It acems<br />
rs:asonabk to suppose that some of thtse wert in<br />
fact svnokess and may have brrn erroneously<br />
dauificd as aon•unoken kad onl) one tourac of<br />
information been tr,cd It was also noteworthy that<br />
there was quite a strong corTClatton in our audy<br />
between actrvc and passive tmoktnF As illustrated<br />
in Tabk Vt, turrent smokers were considerably<br />
more kikely to be eat,oscd to yuive amoke<br />
cnpasure at home (from aourm other than their<br />
own ciE+rettes) thnn were t.ever or ea-smokers As<br />
sw,cd above, this corrcl.tion,' coupkd with some<br />
tnisclassification of smokers as st,on•unoken, tmay<br />
spursously intLte the estimate of risk related to<br />
passive smoking It is important to carry out<br />
fonher studies fo obtain more atxurate information<br />
on rtlublltty of statements about smoking habits<br />
benusc of this pocsibiltty of bus .<br />
Littk other evidence is availybk ebneensinf the<br />
rs:lationshif+ brtusen passive smoking sad risk of<br />
the other ta,okin=•assocsated dtseases in (adult)<br />
bon-mnoken and much of this is open to criticism<br />
(n kis original paper . Hiraysmn (19E1) presented<br />
tttativc risks of doth for various diseases for Ron•<br />
tMrwkinE women aacardinj to the Isusband's<br />
rwnokinj Isabur based on a total of 5b deaths, a<br />
dight positive trend tor emfshysema and asthma<br />
tras twt ttignificant, wfiik, based ou a total of 406<br />
•caths, uo indiation of a uend at i,n was aern for<br />
i.chaernic lrean disrase ta a Osttt paper, (xsad on
5<br />
tw f w k•Ef ff Y/<br />
Ts4L Vt Rciatts ndd, at Aav+nE rs .uvc snwt,r npowrc rt Romc sowrd,n{ to<br />
/.atrent'> n.n x+.nu(anurc.f rtprettt smtdrng AaNts (standardtsed k+t ait last -<br />
~ comMned ci.s 1 and 2 cvntrtJst<br />
Rrtatrrr .f/% W', rnqfuirwr lswurs)<br />
Daw awlrpc hsl+a~ illalr jIA41r<br />
Ne .cr t 1<br />
Fs 125/n1k.1 Rit 11M4Rh tRt}<br />
Currcnt s .Oflf 2 67-5 fxt 2 51l l 74-3 62 1<br />
Ci .syuareJ k.r lrcnd t2df)<br />
r<br />
$1 .t 1<br />
Jrrds<br />
were current smokers Sandkr e+ a! (1985), in s<br />
czsC
l<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Rtf<br />
ALDI RSl1N, M R, LL1 . F N l M AN( ; R(iM~) Ra11 of<br />
lunX anm, ehrunK b+onchrtn, .ch .cmK hc .rt dracasc<br />
•nd strDle M eelatwn 1o lyi.c Of oK.arctta analw! J<br />
C~ Nlrh , 74, 2aa<br />
RRESIAM . N C S DAY, N E(IKO) Su/u/KS! A(rtM.ts M<br />
Cr..4r R-unrA I'.d I- T7.r Awal,W .J Cav-r .wr .d<br />
S+dwi InlcrYUtsonal ARrra7 (or Raorch on CAnccr,<br />
L>on<br />
RUFFLER . t A . MCKLE, L w' . MASON, TJ a CONTAI!'f .<br />
C(111a1 The ausn of tun( onon w+ Tc .u In lr+rt<br />
C.Wrr C..wr wsG frt.ewr .M, Muxll. M l Gxtn .<br />
P (edi) Vcr(al ChcmK InltiNlwnal InC<br />
Cf1AN, M'C (Rtt2) ZLhkn aw Honjlong .1li ..rA MrJ<br />
k' ..-A . 12IC 16<br />
CO#RLA, P . MCKLC . Lr'_ FO+.T/AM E . LIN . Y . a<br />
HACNS7.E.1.. M' (I11)) Pasu .e rewlsnE aRd lunt<br />
anacr L.+nt . Y, 595<br />
DOLL R a rLYO . R(147/) C.Farctu emolrnl aRd<br />
lptonchul aranoma Iou and Lmu reLsanahrps<br />
amonl rc/u(ar vnolcn and 4fcloni Ron•eewicn J .<br />
Ep&A'n+ C.wn Hfrh 13, 703<br />
GARFINKEL . L(1911) Tsnx lrs*sds in Wnj oket<br />
swruhty amonl non•vnolen and c Roie e+n pw .c<br />
Rnwlmg J N.rl C.rurm littu . M, 1061<br />
GARFFlNKEL L, AUERRACH . OA lOUDCRT, L(1"5)<br />
Invo)untary Rrnolinj and lunl onar A ar-0onlrol<br />
ttudy J Natl C.•rrn ltiu , iS, 46)<br />
GARLAND . C, RARRCR•C'ON'NOR E . tUAREZ L .<br />
CRIQUI, M H A wINGARD, DL (1915) EfraL of<br />
pauive Imolrnj on nchcmrc Ac.n dlscase nwrtahty or<br />
Ron•anolen Aprosf+ectrve Mldy Arwrr J . f,pfrM .<br />
121, 645<br />
GILLf3 C R . HOLE . DJ . HA%LTHORNL, V M t aiOYLE . P<br />
(19f.J) Thc eiiccr of environnxnul wbaoto rmoJ
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
10
Shimizu, H ., Morishita, M ., Mizuno, K ., Masuda, T ., Og-ura, Y .,<br />
Santo, M ., Nishimura, M ., Kunishima, K ., Karasawa, K ., Nishiwaki,<br />
K ., Yamamoto, M ., Hisamichi, S ., and Tominaga, S ., "A Case-Control<br />
Study of Lung Cancer in Nonsmoking Women," Tohoku Journal of<br />
Experimental Medicine 154 : 389-397, 1988 .<br />
Shimizu, et al ., reported that, in their case-control<br />
study of 90 women in Nagoya, Japan :<br />
Passive smoke <strong>exposure</strong> at work was not clearly<br />
associated with female <strong>lung</strong> <strong>cancer</strong>, although<br />
the relative risk was slightly elevated (RR =<br />
1 .2) .<br />
That reported relative risk was not statistically significant .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
rA1<br />
T~h,dcu J exp Mwl I :av+ 154 as', 1' 7<br />
A Case-Control Study of Lung Cancer<br />
in Nonsmoking Women<br />
HIROYC'K1 CHIM1ZL' . MCNEHIKO MORI5HITA,' K.ITSCI'L'kl<br />
111zC'r:o,t T.{KAo MASC'DA . : 1'l .•K1o OGCRA,: ailYSCHir :o<br />
SA`7TO,Z MINORC' `15Ht>1CRA .i KAZCO KC\ISSI>!A .<br />
KAZCO KARASAtt'A . KEtSC'KE "ISHIWAKI,V aIASAHI};0<br />
YAHAIJOTO .' vHIGERC HISA>ticHt aild SC'KETA?il<br />
ToxtNAC,t'•<br />
Drpart,nnrt of Public HraltL, Tohokli CHiucrttty School of<br />
.1lulicinr . Sr,ldai 980 . 'tht Second Ikpartment of Inttrnal<br />
.llrrflciur . \'nq~oyn City I'>rilvrsity, .llerficai School . Va•itht<br />
bw (fitle 171f .S . Code).<br />
S89<br />
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COPYti661 U4M` (T1Tt,E 17 U .S . COui .; ~<br />
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http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
3fl0 H . 6himisu et .l .<br />
The causes of <strong>lung</strong> <strong>cancer</strong> in Japanese women have not been clearly<br />
identified . It is widely accepted that cigarette smoking is eaueally associated<br />
with <strong>lung</strong> <strong>cancer</strong>, but the increasing trend in the incidence of <strong>lung</strong> <strong>cancer</strong> in<br />
Japanese women cannot be explained by amoking alone . The proportion of<br />
smokers among Japanese women tamained around 15% during the last thirty<br />
years (TominAga 1982) and the most predominant histologic type of <strong>lung</strong> <strong>cancer</strong><br />
among them n•as adenocarcinoma, which was considered to be more n-eakly<br />
associated with smoking as compared to <strong>lung</strong> aancer of other celJ types (Shimizu<br />
1983 : Takamurs et al . 1986 ; Shimizu et a] . 1986) .<br />
Several studies have been oonductcd with emphasis laid on paaaive smoking<br />
and <strong>lung</strong> <strong>cancer</strong> since the first positive results were presented by Hirayama (1981)<br />
and Trichopouloc et al . (1981) . Some of these studies showed a clear association<br />
of passive smoking with <strong>lung</strong> <strong>cancer</strong> (Correa et al . 1983 ;(3arfinkel et al . 1985 :<br />
Akiba et a) . 1986 . Inoue et al . 1986) . However, the resulte of other studies were<br />
,<br />
equivocal or negative (Garfinkel 1981 ; Kabat and Wynder 1984 ; Koo et al, 1984<br />
Wu et al, 1935 : Lee et al 1986) .<br />
This paper reports a casrcontrol study of <strong>lung</strong> <strong>cancer</strong> in Japanese nonsmok-<br />
ing a•omen, in which passive smoking and other factors such as occupational<br />
histon• . domestic heating system and dietary habits were investigated .<br />
MATIRIALS AYD MITHODS<br />
Our n~k> tronsistcd of female patienu with primary <strong>lung</strong> <strong>cancer</strong> who were treated in 4<br />
hospitals in Xato .ya from Au6ust 1962 to July 19&S . One of the bospitals (Aiehi Cancer<br />
Center Huspitall Fas a <strong>cancer</strong> boapiul and the eetaainins tbree were seneral boepttak<br />
V,tgoya is th, fourtC largest city in Japan .'itb a populauora of 2 .1 milleon and located in<br />
the nliddl~ of the mntn itland . Honshu<br />
During the rbot•e period 118 female <strong>lung</strong> <strong>cancer</strong> pati•enu ecere patbologically identifxd<br />
The ph .yiicun ; or nurscs uled all of them to fill in a qu .stionnaire for taia study on tbe first<br />
or second dat' of admt>sion to the hoapttals . Out of 118 <strong>lung</strong> <strong>cancer</strong> patients 4 refused to<br />
fill in the que>tionn .tire and 24 reported tdat they were current or enmol•ers . The nmatntng<br />
90 nonsmoktng pattenu were selected u the eaan for the following aael .ats . The<br />
questionnaire tnainl}• consisted of tbe questions about rmoking, oceupation .l history,<br />
dietan• hrbic :' personal disease hiatory and about the kinds of fuel for ooolcing. M rsEards<br />
passtt•e saaking we asl• .d them about the smoking habiu or the number of eiiarettes<br />
smoked per dar by p.renu, eiblirtgs, children or husband's parenu in the home . We also<br />
asked them about the length of time which the wonun spent with her husband in the same<br />
room, the period of married life and the number of eisareues smoked by her husband . The<br />
passive stuoke <strong>exposure</strong> at working placea .cu awseaasd only in terms of the prossnoe or<br />
absence of smokers . As regards dietary history, we asked the frequency in noent 6te years<br />
of intake of food items and dirid.d into four esss#ories (no intal-e, l or 2 days ; w .ek, 3 or<br />
4 days week and almost even• day) . We aaled directly the number of giaus of milk and<br />
the number of onutftec tal•en pet week .<br />
The 90 <strong>lung</strong> <strong>cancer</strong>s included 69 .deaocarcinomaa (77y,), 13 spuamous eell c.reinomas<br />
(14°,.al . 4 large cell earcinomu (1a/,), 3 tma11 cell eareinoma (3°a) and I adenoid cystic<br />
ea.rcinoma (11,1 The number of e.w in the age poup of JO-39 . 4049, 50-59 . i4-69 . 70i9<br />
and t10-rears were 3(3° .), 16 (l7%) . 28 (31° .), 27 (30%) . li (16°,41) and 2(2° .a)<br />
tespertivelc The minimum and maximum " of the wes were 35 and 81 ysan and those
I<br />
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Rt
392<br />
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H Shimuu et al<br />
Tutt 2 . Mat= risib of lwnq canen ix aowswoks'rey<br />
vo--en ~6r sr.okinp by wothe+ sw1 kusbnad i<br />
latAe+ u W Ao.W<br />
&moLir>; by husband's father<br />
(-) (+)<br />
1 .0<br />
f .9•<br />
SmoL•ia6 by ootber (- 1<br />
(+) 6 .3 2 .8<br />
•p
t RuG Factors for Female Lung Cancer . 393<br />
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TAtat[ 4 Relatire nsks fRR) of h.ng eanar in<br />
monsnsol'lny soornra for type of howeholri<br />
Araring sysu+n rxd tr nant yean<br />
Type of household Frequency in<br />
beating system controls (?o)<br />
RR<br />
Gu 32 1u<br />
Kerciae ne 66 1 .6<br />
Coal or cbarcoal 8 1"<br />
Tut.t5, Rrlatia risl•s fRR) of fu%q eonerr di nmvmolrNg ro~eN tR<br />
relation to tAe .elrted Joctors /n = 65)<br />
F .ctor<br />
RR<br />
Crude AdJuseedt<br />
Srmoking by tuother in the home 30 2 .1<br />
Stnol•ing by husband's fatber in the home 3 .5• J ._•<br />
Occupational <strong>exposure</strong> to iron or other metals 2 .8 1 d<br />
tRR of each factor adju.sted for other two facton after excluding the patrs<br />
in which one of the facton had unknoa'n values<br />
•q
394 li . Bhimisu .t al .<br />
places<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
In this studr we found a po.itive association between <strong>lung</strong> eancer in<br />
nonsmoking women and the smoking hutory of family members, especially that of<br />
mother and husband's father. As Japanese children nsually spend much longer<br />
time with their mother than other family members do, mother's smoL•ing may be<br />
a representative index of passive smoking before leaving home at around 20 years<br />
of age Rerently we found that the saliva cotinine level of nonsmoking school-<br />
children is not high when their fathers were smokers but high when their mothers<br />
were smokers in ~Iiragi, a district of northeastern Japan (unpublished data) .<br />
After marriage, 35°0 of women in controls lived with their husband's parents .<br />
The final proportion of control women whose husband's father smoked cigarettes<br />
in the home n•as as small as 8%, but that (18%) of eases was somewhat larger .<br />
The husband's father may have retired already and may have stayed home much<br />
longer than the husbands . There is a possibility that Japanese women may be<br />
more frequently exposed to the smoke of cigarettes by their husband's father than<br />
that bv their husband .<br />
Ft'e assessed the total length of period which a woman spent with her husband<br />
from the length of the period of marriage and the hours during which she lived in<br />
the same room . but no difierenoe was found between eases and controls .<br />
No dose-response relationship was ob.crved between the risk of <strong>lung</strong> <strong>cancer</strong><br />
and the history of smoking of mother or husband's father . Usually the respondents<br />
remember .rbetber their mother or their husband's father were smokers, but<br />
they may be unable to recall the exact number of cigarettes smoked by their<br />
mother (especially in childhood) or husband's father in the home .<br />
It has been suggested that bet .-caratene and preformed vitamin A decrease<br />
the risk of <strong>lung</strong> <strong>cancer</strong> (Smith 1982 ; Hinds et al . 1984) . We asked a very simple<br />
question concerning the frequency of green-yellow vegetable intake, which has<br />
been referred to as a protective factor against <strong>lung</strong> <strong>cancer</strong> in a large cohort study<br />
of Japan (Hirayama 1962) . No association was observed between this variable<br />
and female <strong>lung</strong> <strong>cancer</strong> risk in oar stody . Most of the respondents had green-<br />
yellow vegetables very fr .quently and we found no difference between casss and<br />
controls . There was no do .e-response relationship between the frequency of<br />
intake of Ereen'yello.r vegetables and <strong>lung</strong> canoer risk .<br />
We also assessed the effmacy of vitamin supplements over a period of more<br />
than one year in this analysis, and found the risk of 0 .5 . However it was not<br />
aatistically significant .<br />
Other dietay factor such a : .itamin C and cholesterol may be tslated to the<br />
development of <strong>lung</strong> eaaoer (Hinds et al . 1983, 1484 ; Byers and Oraham 1Q83),<br />
but no appreciable association was observed between the risk of <strong>lung</strong> <strong>cancer</strong> and<br />
the intake of food items listed in this study . To evaluate the effect of dietary<br />
habitc . more precise measurement of food intake is needed .<br />
A slightly elevated risk for disease history of silicosis is consistent with the
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kii-ome bias in our study . Lung <strong>cancer</strong> cases were not derived<br />
from general population but from the p,uientF of a limited number of hospitals .<br />
The proportion of adenoc,rrcinornn patient, in our aeries was ten percent larger as<br />
compured with that :n total <strong>lung</strong> <strong>cancer</strong> Itatieuts of this area The proportion of<br />
scluamons cell carcinoma shotced in npposite tendency (Kar,uaR a 1983) . We<br />
electPd the control ; from the same hospitals considering that both cases and<br />
controls in is Qnte hospital may have similar backgrounds . Hon-ecer . one of the<br />
hospttal uu-, a can, - Itn,Nital and we had to include many breast <strong>cancer</strong> patients<br />
in the controls For this re .t~on we compared the status of passive smoking among<br />
the brrivt <strong>cancer</strong> patients with that among other controls . but we found no<br />
difference . Futthermore, the risk of <strong>lung</strong> <strong>cancer</strong> for the survivors of <strong>cancer</strong> of the<br />
brew~t a,>_< not high when assessed by the data of a population-b,ued <strong>cancer</strong><br />
rrgistn (Takano and Okuno : personal communication) .<br />
Our study showed that the exposura to tobacco smoke from household<br />
members (i .e., mother or husband's father) could be associated with female <strong>lung</strong><br />
<strong>cancer</strong>. As the precise situation of passive smoking in the home or other places<br />
is still unclear, further studies are needed to clarify the significance of passive<br />
smoking in relation to the etiology of <strong>lung</strong> <strong>cancer</strong> in Japanese women .<br />
AtknowkdQments<br />
We are ftrnteful to Ms K Htrose of Aichi Cancer Center Reaerrth Institute and Ms . Y .<br />
T,tl::ihwhi of Tohoku University School of )ledicirte for their technical assutance . This<br />
atudy x aa supported by a Orantlin-Aid for Cancer Research from the )linistn of Health and<br />
Welfara ((',nsnt Number 57S )<br />
I) Al :itw, 8.. Kato . H:. k Blot. WJ . (1986) Passive anwlialt and lucsE canoer among<br />
Japanse romea L4rar . iiw .. K . d8W-4807 .<br />
2) dreslow, N .E. k Day, N .E. (1990) The analysis of ore-sotttrol audiea . In :<br />
Statistaos/ Yei" it Ca,Ker Rres>ti1 . Vol . I . IARC Scientific Publicatwns No . 32.<br />
laterrutional Aratcy (or 8tiarah on Cutaer . Lron .<br />
3) Breslow, N .E .. Ihy, N .E .. Halvonen. K .T .. Prentice, R.L. k Sabet. C. (197B)<br />
&timatioa of asaltipk telaeire ewl trJnctiocr in eate!»d eaar couuoi studies .lswee .<br />
J . B/iJcrwiot . . 1M, 299-J01 .<br />
4) Byers, T. k Graham, 8 . (1084) The tpidemio)oU of diet and canaer. In : Alrauar<br />
in C4rcrr Rneoral, Vol,11, trditad by G, Klein k S . Weinbous+e, Academic his,<br />
4riando-Fbrida, pp . 1-60 .<br />
S) CorreA, P ., Picl-le, LW, lroatham, E ., Lin . Y. k Haeasttl. W. (1pdJ) Pa:ioe
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
396<br />
H Sbimitu et a) .<br />
staol•tne and <strong>lung</strong> canoer . Laacrt . 2 . S9S-597 .<br />
6) Finlelftein, M Kuaiak R . k Suraayi, (7 . (1982) 1Lottaliq aawng ciaen rttroei .int<br />
a-ori:nxn'a ootapensation for ailteosu in Oatatio : 1940-1975 J• actyp -11ed ., 24,<br />
66J•66"<br />
7) C.+rfin{;al . L . (19,i1) Tttae tnnds in <strong>lung</strong> <strong>cancer</strong> tportality amonj tsontmolert urd a<br />
note oo pulis•e aaioltng J . Mat . G=Km IRSt ., M, 1061-1066 .<br />
8) Uarfinl:rl, L, Auertach, 00 k Joubert, L (1985) Lo .olantary tmoking and <strong>lung</strong><br />
canc.r A ca.rcoutrol study J . .at Cancsr laat ., 75, 4b3-469<br />
9) Htnds If W ., Kolonel . L .N ., HanL•ia, J .H k Lae, J . (1983) Dietary cholaterol and<br />
<strong>lung</strong> <strong>cancer</strong> rial: in a mu)txthnic population in Ha .aii, lat . J . Canu+ . 31, 727-732,<br />
10) Htnds . >l .W ., Kolooel, L.N ., Hankia, J .H . k L.e, J . (1964) I?ietary vitamin A .<br />
crroten-, vttaatiu C and risl of <strong>lung</strong> raacer in Hat :ail A .a.* . J . lpede*etol ., 111,<br />
_'•=-•23 ;<br />
11) Htnrema T(1?41) NonarnoLing rivea of beavy smokerza have a higher ruk of <strong>lung</strong><br />
canc r .1 studY from Japan Bnt m.d . J ., 2{2 . 183-185<br />
12) HiraYerna . T(19d'2) Epidemto)olpcal upecu of <strong>lung</strong> <strong>cancer</strong> in the Orient . In :<br />
Lung /anorr 195 :.' . edited by S Lhil:•arca, Y . Hayama A K. Suemasu, Ezcerpta<br />
lled ca Am :terdam-0zford-Prtnceton, pp 1-13 .<br />
13) Inoue R Ohuula . T . . Shimura . K . k Htrayama. T . (1986) A ase-conarol study of<br />
<strong>lung</strong> <strong>cancer</strong> Luag Car«r, 26, 763-767 . (Japanese)<br />
la) Kabrt . 0 C . k 1t't•nder, E .L (198a) Lung <strong>cancer</strong> in noaamoJcen . Csaeer . 53, 1214-<br />
1321<br />
15) K .ruawa, K . (19d35) Distribution of histalog•'scal typa of <strong>lung</strong> <strong>cancer</strong> in Aichi<br />
Prefecture Jap J CAot LL . . 44 . ®09-813 . (Jap.ne.e)<br />
16) Koo, L( . Ho . J .H . k Saw, D(1984) L passive atnokina an added risk factor for<br />
<strong>lung</strong> <strong>cancer</strong> in Chineae sottxn J . sp, elin . Capzer Ra ., 3, 277-283<br />
17) Lee . PN . Chamberlain, J . k Alderson, H .R. (1986) Reluion.hip of pasive smoking<br />
to n,l; of <strong>lung</strong> <strong>cancer</strong> and other amolcing• .uociated di+eaus Brit . J . C4KCe* . $4, 97l05<br />
18) LS•nFe E . Kurppa . K ., Kristoferson . L ., Maller . H . k Sauli, H . (1986) Silica dust<br />
rnd <strong>lung</strong> <strong>cancer</strong> Results from the Nordic oecupauonal mortality and <strong>cancer</strong> incidence<br />
relritteri J . r,at Cancs+ Iru( ., 77 . 683-889<br />
19) >lat :ukuri, S. . Tomituso, T ., Kitano, N ., Seino, Y ., Hamada, H ., Uebihashi . M . .<br />
\akajima, H k Htrata, Y . (1984) EEffects of environtnental tobacco smoke on<br />
unn.n• cotinine eser.tion in aottsmokert . Evidence for paaice amoking Veu<br />
Engl J .lled ., 311 . E28-832 .<br />
20) Nalatoura . H ., H.aaai, A., Fujimoto . L, Matauda, M. k Tauithi, R(1988) Relation•<br />
•hip between amoL•ing and the four najor hitiolofic tTpes of <strong>lung</strong> <strong>cancer</strong> . Luag<br />
r'nru.r . 26 . 137- l 1d . (Japus . .e )<br />
:l ) Shimizu . H . (1983) A un-oootrol study of <strong>lung</strong> canoer by histulogic type . L+tng<br />
Cax
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Ri•k F,trt,v• for F--iu,il, LuuR C .uir,r 397<br />
13a-'131<br />
: t µ'u . A .H . . HeuJewn B E . Ptke, \I C~ l*u 1l (' ( If)tt)l ~ntuktnc uttKr nal :<br />
fuuurs for luug cuu"r in wow.n J~nr f.„rcr lKit, . 74 , ~7 al
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
11
Stockwell, H .G ., Goldman, A .L ., Lyman, G .H ., Noss, C .I ., Armstrong,<br />
A .W ., Pinkham, P .A ., Candelora, E .C ., and Brusa, M .R .,<br />
"Environmental <strong>Tobacco</strong> Smoke and Lung Cancer in Never Smoking<br />
Women," Journal of the National Cancer Institute 84(18) : 1417-<br />
1422, 1992 .<br />
In 1992, Stockwell and colleagues published data from a<br />
case-control study of nonsmoking women in Florida . The authors<br />
wrote : "We found no statistically significant increase in risk<br />
associated with <strong>exposure</strong> to environmental tobacco smoke at work ."<br />
However, they failed to present the data associated with this index<br />
of <strong>exposure</strong> .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
I<br />
h<br />
1<br />
Environmental <strong>Tobacco</strong> Smoke<br />
and Lung Cancer Risk in<br />
Nonsmoking Women<br />
Hcathrr G . Stuckts•cll,' Allan L .<br />
GaJdtnun, Gur), H. Lyman,<br />
Charles 1. Nuss, Adum Iti' .<br />
Arm .ctrong, Putriciu A . Pinklrntn,<br />
Elizabcth C. Candclora,<br />
Marcia R . 19rusu<br />
t .ckrrounQ: Exposure to environ•<br />
tseatal tobacco smoke (passive smok-<br />
I.t) has bcen suggested to be a cause<br />
•f <strong>lung</strong> <strong>cancer</strong>, although eariy epide•<br />
ot.logic studies have produced Ineassistent<br />
results . Pa s .d tlrouatts- `~<br />
tict, Colktr of iwbtic Hcaln, . U .i .crstty ot >;ana<br />
Fsaeid, . t.mo.L n- 3xtiAsrac . ~.f<br />
CA<br />
RErOR75 la l7
csrciaomt of de IYnj (latctaatlosl<br />
Ctauifrcalion of Diseases for OwcoloYy<br />
Codes 162 .2•1629) that wu Iuinosed<br />
•et..ten April l, 19E7, sad fcbnary, 28,<br />
1991 . and if they resided at tMe time of<br />
Iiapnosis in a 2K'-ounl ; area ia tratral<br />
florid . These women ucrc idcnlified<br />
tlrrourh the tumor rcFisuics of area "•<br />
iaital% and thc floriJ . Canccr Data SW<br />
t,cm of the Statewidc Cancer kcgrstry .<br />
Conuol s,ubjects wrrc community bascd<br />
sad Mcrc identificd through rsndom•<br />
Jijit dialing All casa patients and con•<br />
trol .uhjccts Mcrc lifetime rMnsmol .erN .<br />
cLcfineJ as Iuvint unnkW fcx a totat of<br />
k~a than h snonths nr kavinj a>rwlcd<br />
(cxs shan tfpl cijarcr(cs in thcir Iifc•<br />
timCs<br />
The umr+lin ; status of potential nac<br />
ptient, in the atudl was enn(irrned at<br />
teverrl at .~ca Oncc Shcr,e individual,<br />
wer : iJrnriG,;J hy thrir hrrspital crr thc<br />
Statcw idd C'aneet Kcyi .tr) rceord .,thcir<br />
ftmolink status was eunfrrmcd when<br />
their physician wa .s eonl .cted fur per•<br />
taission to interview, again at the time<br />
of initial contact with the patient or nezt<br />
of kin, and, finally, at the eommence•<br />
ment of Ihc interviev . . In adJirion, the<br />
laten'uw eontained questions retardinj<br />
esperimentalion with tobacco, desijned<br />
b elicit in a aculral rnanner any prior<br />
trndisclosed tobacco use Any potential<br />
case patient whose smoking ssatus could<br />
wot he confirmed vvs escludcd, Of<br />
thou found to he eli=ihte, e0% of ths<br />
eut patients or their nezl of kin agreed<br />
to Ix inlerviewed The tmol•inj itatus<br />
of eonarol wbjocts w as determined dur•<br />
int random-di;il dialint and verified<br />
during the interview .<br />
Trained inurview•ers inurviev.ed casc<br />
paliertss and control subje<strong>ets</strong> either in<br />
pcrson or overthc telephone . When sec•<br />
essar% . questionnairca wcre ruiled . Of<br />
the ease palicnt inter .•iews, l1'>E werc<br />
obtaintd hy in•person eorsuct, 51% by<br />
kscphont, and 8% by mail . Of the eon•<br />
tro! tubjen interviews, 53•8rl %LYre ohuine<br />
;i by in•person contact, 15 .9% by<br />
teiephone, and 0•34E by aaaii• tatormed<br />
cvnsrnt was obtained from t1u esic pa•<br />
tienis and control tubjens prior to the<br />
intcrrie>~s according to the guidelines<br />
of the University of South Florids inui-<br />
Wtional Revicr< 8oard, The iaterview<br />
i.cludcd questions on environmental toa<br />
bacco cmoke esposures at bome, on the<br />
)o6, and in aocisl uttings . IJ csse pa-<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
tieasa were bo 11I b be iwservitaed tx<br />
wcre ieceascd . aurroiau teapoadcats<br />
(prirnarily ltusbands and children) were<br />
satcrvicwcd toterviews of tunotste ntpondenu<br />
were .ecxsury (or 66 .7'!E of<br />
the case patients<br />
Odds ratioa (OiCs) were calcutsted to<br />
csuimate the relative risks Multiplc bo••<br />
gislic regression analyses were per•<br />
(ormcd using the SAS L.OCi1ST7C procedure<br />
(SAS Institute . Cary . N .C .) .<br />
Nlnety•fiive pcrccnt cortfidencc imcrvala<br />
(Cii) were calcvlated from tMe lotistic<br />
tnod<strong>ets</strong> . The chi•square statistic was<br />
wcd to text (or trcnd,<br />
Ruults<br />
The stud) p{omewkal oldet and lud fewer 7tart<br />
of tomul .ducalion thu, vontrols, with<br />
a tijniftcam trend of is,creuinj <strong>lung</strong><br />
<strong>cancer</strong> risk with dccreatint years of<br />
fchoolint (P . .tl19) AMwss half of the<br />
uu patients and control tubjcns irad<br />
lived in Florida for at ieasl 2/) years<br />
Table 2 iwditatcs the OKS and 459E<br />
Cis associated with ezposure to cig .•<br />
rettc tmokc fsom parenti, tihlinta, Au .-<br />
I+ands, and o(her Isauuhold membcn,<br />
after adjuslment (nr age . racc, and<br />
[ducatKfn . UnctpncCd Kdividual, wcrc<br />
Ua.c with ae lanuscbold envirrmrncntal<br />
tohacco unokc etpowre, Wc der .crihc<br />
<strong>exposure</strong> i . ecrnu of uswkc•ycar ., dc•<br />
fined u• the sum of the reporscd years of<br />
e :pnaurc to eitarettc tmnkc (nxn each<br />
amnker in thc househnld We rnnxidcred<br />
arswlc•ycan% to hc a moee reliable rr.casarc<br />
of exposurc than pack-years, aincr<br />
ttudy panicipants had ltss difficulty realling<br />
tha Rumber of years they lad<br />
lived with someone WMo uenoked tlsan<br />
recalling the tsurnber of cigarettes per<br />
day to which they had been ezpoud•<br />
Smoke-years were subdivided into thres<br />
eatejories of approxienately equal size<br />
Tal6k t . OnarRrmw~ st sIw_w1 cMnaneriwic. a( are rrinw "/ tata.eni WAJcV .<br />
C ... Mrir.n ( . . Ztnt' C.wnt ..b)cet. ( . . jUl)•<br />
Ca.raar+wic r~to s !+o ~r<br />
l,cr<br />
wt
1or both wfy aad adult years . Tis distribution<br />
of unoke•years of exposurc<br />
vas snuch lowr:r tor sarly ytan, pri•<br />
wrily beeause ptrtieipents te*ded to<br />
/ive with tpouscs for anorc ytan lhan<br />
Mey had lived with their parents• rtar+lt•<br />
404 in bwer eutoff points .<br />
Lant <strong>cancer</strong> riek estimstcs for .vomen<br />
who wcre ssposed to environmr :asl<br />
Iobacco smoke during childhood and<br />
sdolcsccncc sre shown in Table 2 .<br />
When we cakuh'ed the tisk sstociated<br />
wUh esposure to smoke from family<br />
wcmhers on an individual hasis<br />
(rwother, Athct, eihlin=s, and others) .<br />
Mcrc wes a slight incrurc in risk fnt a11<br />
trrfwx.ura., althtw ;h the inerea>,e% ir, rial<br />
were t+nt tastiraically sitnificant . F1e+w•<br />
e.rer . %%hcn we alculated risk ncewdin ;<br />
1o cmcste•yrars of expowrc, which rc•<br />
lkn,, total ccpcrwrc to unokc from all<br />
brw .cMilJ memhera, a >itnificantly clc•<br />
raled ri" of 2 .4 (9S'% (.'1 a i .l•5 41 was<br />
ot+aervcd for women expoacd 22 years<br />
4111' more .<br />
Table 2 also shows the effect of en•<br />
wironmcntal tobacco smoke exposurt<br />
iurine adulthood on lun; <strong>cancer</strong> risk .<br />
Women who lived for 111 or more years<br />
ef their adult lives with husbands and<br />
•ther individuals who smokcd were<br />
found to Iavc ae elevated risk of 2 .4<br />
(95'i ta a If we eonsidere.d<br />
only smoke <strong>exposure</strong> from husbands tor<br />
40 or more smoke•years (data not<br />
shown), the riek ealimate deereascd<br />
slijhtly to 2 .2 (95% Cl ∎ 1 .0-4 .9) .<br />
Is terau of sout IiGetiree rrsaoke•ysan<br />
ot expcwrs (Tabte 21, ao nIt+rifresst exaeu<br />
risfs were obterved for wornen re•<br />
pning fs+ver than 40 liftsirwe saokt•<br />
yean, but wwnen teportinj 40 oe teore<br />
years of <strong>exposure</strong> experieated an e)e•<br />
vsecd lrng eanrer risk of 2J (959E l:.•l .<br />
1 .1-r .6) .<br />
We elso r:xamined the relationship<br />
between the <strong>lung</strong> <strong>cancer</strong> ritk assotinted<br />
with environmental sobaceo srnokc es•<br />
poaurc and lun ; <strong>cancer</strong> tslliype . Sinct<br />
61 .4% of the <strong>lung</strong> ancen is the study<br />
were adenocarcinomas, all fant anr:er<br />
kiuolotien orher tMn adenesrareinoma<br />
wore enrnhined in one graep for anal•<br />
yxi>_ Rie,k craimatcc for snu+k.c-yeara of<br />
expn .urc were aleulated esparatcly kx<br />
the two Croups, and (he results arc<br />
shown is Table 2 .<br />
Pot womcn h ith .denocareinorna . the<br />
risk& wcre sJiFhti) elevated for all ate-<br />
Rnric+k of smoke <strong>exposure</strong>, fwt the tccuitt<br />
did sot achieve ttatistical<br />
significance . Women with fwn•adenoeareinoma<br />
lunt ancert, on the other<br />
kand, showed sitnificantiy elevated<br />
risks when their <strong>exposure</strong> to environmental<br />
tobacco smokc was of lonL duration<br />
. The OR indicated a threefold<br />
increased risk of <strong>lung</strong> <strong>cancer</strong> (or women<br />
who rcponed 22 or more rmoke•years<br />
of <strong>exposure</strong> from parents, siblints, atxM<br />
others during ehildhood and adolee•<br />
ccncc (OR ∎ 3 .4 ; 95% Ct .<br />
Similarly• women with 40 or more years<br />
of adulthood <strong>exposure</strong> to unoke from<br />
Iwrxbands aad oeb,er bo.es>rotd a.pwkery<br />
s:pcrie .ced a eignifieaat <strong>ets</strong>vatioa is<br />
risk (OR a 3-3i 95% CI a 1 .1•4 .1i3 .<br />
Wken total lifetiRne sspoars to savironmental<br />
smoicc was otesidend, thc<br />
ORwas3 .3(95teCt .124 9) tarthe<br />
lriRhest expowre kvtl, for womea vith<br />
rron•sdenocarcinr+ma lurti <strong>cancer</strong>s, there<br />
was a statiuicatly sipnifirant trend of<br />
iracrcasing risk auaciatcd with incrsasinR<br />
smcrke•yean of sxposnrr for each<br />
typc of e :posun (cfiildhood . adulthood,<br />
.nd lifetime) .<br />
Sinee sunoCatc rrspowdents wcrc required<br />
for ahnut two IAirds of the ea .c<br />
paticnt intcrviews• we iaveslipatad<br />
w#cthcr the fknuree e,f the ar .e pallent<br />
intcrvicw (xel(-respnersient verwe, wrrn•<br />
5atc re4ondcnt) sffened the riik cFtitautex<br />
. Surrogate rrspo .dra,s for cau<br />
patients were divided iato two jroupt,<br />
"Muxhands" and "oaher surrngate% ."<br />
the tarter trrwp conxistini ; primarily of<br />
aon,, and dauthten . Tbc tosHlts of Ihis<br />
an..lyaix arr: shown in Tahie ` . $eeauu<br />
the'urnber of respondents ia twme ate•<br />
:oria was vsry srtult, analysis of risk<br />
associated with <strong>exposure</strong> to tmoi.e from<br />
individual household rnemhers is<br />
limited to fathers and (tusbands . In eomparison<br />
with thc risk ectimatcs for<br />
women whose interviews were "m•<br />
pleted by themulva a by ifcir !wsbands,<br />
the ritk etiimata kr woaxn ir<br />
the "other surrogate" respondent att•<br />
sory were eonsidcrably krwer . This rt•<br />
tult wat trve both far tisk associatcd<br />
Ta6k 1 Erren .r cwvitww,cr,ut wd ..csu Wwkr .. Irnj eawnn rn .lc .r r.ea+a .a,kfuj VMta, aetartiq M lrrrrw ta! r)yc<br />
AN Irnt a . .rn AJc.ocmi.awr An ~ crn r pn<br />
kary+art \" .} OR' r :t7 CI / f, . a .+J OR' ..t4 (1 P tw trt*d (TR' trt+} (1 P i,w tre.A<br />
ftpwac "r<br />
f4,4A.y 111, 0 64 1 1* 0< .1.k e 1 .7 40-A•S .2<br />
isr4•r 1-1 rF-2i t .t 6 .9-2c 1,4<br />
tAi ~t, nd .+4crs i 7 qy-1 v 1-1 *s-2.7 tA Rb~ .7<br />
11Jt.1,n r A "2.7 21 s•3ac<br />
tawks<br />
caiuh . .rQ/.dek+cc.a (p.+ra.<br />
~t~~)<br />
tK•21<br />
t F<br />
1 .1 .t2 .a t ,L~A<br />
I t<br />
1 .3<br />
r.4I -%<br />
t.3dA<br />
s»` 2A 1 .1•S .J .tlt 1 .7 ~ .1•,tA .f91 X4 ( .1•IO .F .WI<br />
AMhlu+~ (h+4..& 844 0tficr .t<br />
t . r .. aa A : 1 .7 •tt .7 1 i ts-es<br />
~ .« 14 2b R7-S a<br />
. •+u 2.+ 1 .1-St A..`~ tx 0 .7d .7 ,]r2u } -A 1.1-ls mk<br />
Au NrnW.r rr .,o..td r,~rrrr<br />
r+ •w•2 S 1 .2 . -9 .2 7 1.2 s s•3 .e<br />
1 . 1/.7•s . 1•2 Is • ..as<br />
r. .o t .td F oru I .7 or< .~ . .n1 I2•1~ uut<br />
'OR . aii.rut 4w aCt, raee . ar
Tah/. 1. 911140 ar n.i ....rts1 rir ..et : .. Iry .. .cn ri.1 .l .wrw.i iwt<br />
.rc. .•l. .t w rr..+.e .( wre lr4wi Ire ..w.<br />
ti. .r« .l ar< W•rr Y. .+vier<br />
ieH ( . . 7e,1 k.ai. .J (a . 4x) Orlcr "nSaw t . . 92) IsN w Mabb ( . .)Ixl<br />
(Y .Mw.rc 6u^ry OR• K41~ CI oR• fRf C1 OR' flS CI OR• tt4 f•t<br />
tlar. ..nr' fe+Pao<br />
f .r4y 3 .2 •9•11 .1 2 .t/ .4at.x aA i-L11 27 en•7,?<br />
/MrJ..J<br />
>
i.diated thau the escivsion of adrsoearci.omu<br />
from thcir analysis rrodMcrd s<br />
sutisyitally sitniRtant linear Irrad of<br />
i .crcasing risk with iscrtasiaj ss-<br />
'osure .<br />
!a an i>.vestigation of ao+-adeaoearcinoma<br />
iung ancers in .autnokinj<br />
Athenian women, Triehopoutos st al .<br />
(J!) rcpnncd a risk estimate ot 2 .4 for<br />
women who%c Mustunds smoked itwtr<br />
than 21 citareHCS per day sad a risk<br />
Wirtultc oL3 .4 for women whos< t+us-<br />
Irndr smoktd sore Ilun 20 eijarettes<br />
rer day . As aucoeiation betwees marviajc<br />
to a smoker and an inctuscd risk<br />
of amail-ecll and squamous ee11 <strong>lung</strong><br />
areincrmas wa,; sl .n rshrcrved is a stady<br />
c+f Ss'cdiah womcn (12) For otAcr <strong>lung</strong><br />
canecr ectt typrr, in the SMCdrsh study,<br />
t1c ti/.ks Wctc clo.c ai unity ascspt in<br />
the ea+.c of women with high espou+re<br />
kvc) ., wbkw ri>,k4 wa.s tkluhlyd . A study<br />
trt lifetimc wc/namuking wnmen in HunC<br />
h:anr by taw ct .1, (13) .huWCd that e .roe.urc<br />
/o envimamcnt,ll toMcco smoke<br />
ws.c as,ociated with an elevated risk of<br />
aquamous cell and large-cell eareinomas<br />
. These results conflict with<br />
tho+,e ohscrved in a multieentered study<br />
3s the United States (4), where an ele•<br />
vated risk of <strong>lung</strong> <strong>cancer</strong> attributable to<br />
passive smoking was limited to patients<br />
with adenoeareinonu ; these i>
. / ,<br />
A m.Mke.rsr aasrrarsl M .fr . Cr .arr<br />
(irls hn 1JW),<br />
1901<br />
0) i.aau-w roT, T..a ..ns. WD, v .aa... u•<br />
L4 4L• tUnt irfue! Md teloMSry Y M"aeo<br />
Nr.llc i. nts ls ..uioi4 N Eaj1 J Mrd<br />
fVAV.A,+, twu<br />
MI G+a.. R Fx .u LW, F+wrw.r E r* .u :<br />
Fwivc .wekl .t aad tv .j u+cct IA .ctti<br />
= avt SV), Iw~<br />
(II i..r,wi! 1N' . W,u . .k AJ . kvt .a .. RH<br />
fwntui.c tit r . .! tiisrir.c Fr .+++Y .w .A•<br />
i .t .s c..ceY .+ .1 lycati 1 .ct2-ti" . tM~<br />
V) Wt, AH. Hr~+avr IL P .&i MC, vT a=<br />
j.nliuj s+td a4r rnl (ac„++ i .x b*F tl.,<br />
es 1r su.n .')NCt 74 7J)-7t1 . lwt.t<br />
f•l (5+.+ .+.r N& Iurt, I .W . MA ..r Tl, f-,<br />
u: T1c .dNir wf p+..+s v.i,.; M br4<br />
p.cor esi,err, tte . .n UcY : .,ri11, Iwtt,<br />
eMt Gwsw .at, (- At-v O . M .w at t- M•<br />
.wiWary .riin ; rd ir .i c..cnA ou•<br />
.wrw,i .wir aM(1 t~,ahunv, Iwt~<br />
4111 TlN1M/AMh,M l) . K ./ AAIM/4 I- fr . . . .t.<br />
t-tT u : t .ws c..ctT a.J (w.+ .Y r..ai.F<br />
iu 1 f..ee+ 27 . t .d, Nha<br />
lla r't.rrutu+w . G . elrr .wtt' 1'L li .'t .ncvw, C :<br />
!wd tvnj a .cn M i.eJnA<br />
Aw I k{.wk'mi,~i 12! 17- :J . Irr+r)<br />
/1,1t t: .k . If, 14l JH . SAM D t t .l McewN•<br />
zbc•w. ., tvw.ivc u.w~tnt .wJ Nrnak t~t<br />
VRt CIMVi rlal !II Mt MM• .R+,~I,Ai l~~•<br />
a .+,c rcm,k+ l .r 1 C.nccr 1V IE?-InV, IVl;)<br />
//1i t_nu TH . Ko»to IT, Wn ., . CM . ti ^i' .<br />
t1AN)lifl; . refYiMC Y9,uEMj lr+d kM,11 .gK1l<br />
erpr+ i. It,nt o .cY* is Hont Ka+t Clikeu :<br />
.nw,c. ltr J Crctr 4 :67.Ud7X. IVY7<br />
Second Cancers in Patdents<br />
With Chronic Lymphocytic<br />
Leukemia<br />
LoEs B. Travis,• Rochelle E .<br />
Curtis, Benjamin F. Narthey,<br />
Joseph F. Fraumerti, Jr .<br />
Ieckjroyxd: Reports te dale have<br />
pr.vided widely diverYtat estimatea<br />
sf the risk .f sccond maligaaat .eaplams<br />
la patients with chronic Iysa-<br />
'Mocytic leukemia (CLLI, raatlaj<br />
Ir .m aacer t/eficits to excesses st<br />
twofold to threefold . l+rrpose: Orr<br />
purpose was to ettimate the rlik af<br />
secoad primary eaacers fotiowiag<br />
CLI., t.tlliiiat population-based /r-<br />
•ar retistriet, sad to determi .e<br />
wkether site-specitic excesses might<br />
be ass.ciated with type •r iaitial<br />
lrealsaeat f.r CLL . Methods : We<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
•satysed date f.r pJSf patieats<br />
di:ra .sed wltt CLL as a first priaaary<br />
rxarer `etweea 1173 aad tlit,<br />
who wcrt rsponed te e ..c of sise tYror<br />
registries participatinj la the<br />
Natioaal Ca .cer Iastiiute's Srrvellls<br />
.ce, Epidemiology, sad Ead<br />
Resrlis (SEERt protrasn aad who<br />
atsrvived 2•r snorr sa .atht . SEEK<br />
filet wert scarched for (avasive pri•<br />
wary .uliGoa .cies that developed at<br />
kast 2 snonths aftcr the t.itial CLL<br />
d[alt.rsis. Nes>rtu : Cwnparsd witM the<br />
te .erai popufatioa, CLL patleats<br />
dcmo .strated a allaificaatly (a•<br />
crsased risk .f developi .g all fer .wd<br />
tancer: (tt10 .trserved ; .Asrrred-Ioexperird<br />
rmllo iU/E) a 1 .2tt ; 1Sr4 watideace<br />
i.terval (CIj s Lif-1 t7l >wikalficsat<br />
excesses were • .ted f.r<br />
e.acen af twe 1r .p (O/E ∎ I .f0) .<br />
brain (O(E . 1 .951 . aMd e,vt (Ialrsrecutar<br />
snetaaom :i (O/E a3171 as well ak<br />
mslitnant melanums (O/E a 2 .79)<br />
a .d fiudptJn'i diuau (O/E a 7A91 .<br />
Cancer riti., which did sol vsry sceording<br />
to t .ltial treatmeal tates.ry,<br />
wat also eoastanl across all time ialcrvals<br />
aRer CLL diag .osis. Ce+aelwsionr<br />
CLL patieats art at a sltaiAantly<br />
Increased risk sf developing a<br />
second maiizaant seoplasm . The pattera<br />
•f <strong>cancer</strong> excesset suggests a<br />
susceptibility state pertnittinj the tievetopmen(<br />
•f seleclcd record aaatitsancies<br />
In patients with CLL, perhaps<br />
because sf shared etiolo=ic fad .n,<br />
ImmunofoCic impairstte .t, sad/ar<br />
Nher Influences . Althouth .ur res.lu<br />
do sot sut=est a ttront lreat .eat<br />
eRect, srori detailed studies of second<br />
tumors In CU,L are aeeded to lavesli•<br />
&atc lhe role of radiation therapy and<br />
ehemothcrapy• lJ Nati Caatxr /ast<br />
814422-1427, 1ff21<br />
ratients with chronic ly/nphocytie<br />
kukcmia (CLL) cxhihit a variety of imsnunolotic<br />
pcrsurhation>, (1•I) that may<br />
iacreaae ihcir riik for second malignant<br />
aanplasms . 'flM occurrence of f .milial<br />
Ct.t- snay ai>n sug&eu, for some auh-<br />
jeC1A, `enelic determinantR (S•7)- n.ch<br />
as Ihosc that rnderlie other am of aeui-<br />
/iptc primsry eancers (d.4) . Moreover,<br />
radiotherapy and ehemotberapcrrtie<br />
rtenls tnxy also contribute lo tubsc•<br />
"at trutiSnancics awoRE aarel wrvivors<br />
(10) . h)i islpoeunt to e{arify tlc<br />
risk of sccond nactrs iu CLt patienu<br />
kausc of the potc .lial i.r¢tact ar'a .<br />
/ient ma.s=ement, folloMwp . awd sur•<br />
vivat . liowever, various teporu to date<br />
Aave prewided divcr0eat etuirnatai of thc<br />
nccuncncc nf seccmd malipn .ncic> in<br />
CLt, prticnll, esnting frcxn <strong>cancer</strong> dcfi•<br />
e:itt to cxccar.es of twofold lo ty reefold<br />
To funher expiorc and quantify<br />
thc ri .k of secrnd eaaccrti amnnF a<br />
iarY,: a.snl.cr of CU . patieatk ia lh, :<br />
stnt•~ta) perpulatics. .ad 60 csa/aiac aa>,r .ciatiewst.<br />
af tisk with iaitial IAstaf+~ . ac<br />
ct>t+Juctcd a errvcy cr1' tNCwc tMan WKxt<br />
arrA whjctu. eer.Ntcd k+ th,.• Natinn .t<br />
('anccr (raaitutc' . Survcitlarcc . Epi .<br />
ek:miuitrry . and End llcsult . (SEER)<br />
Prorram' from IV71 thtourh IVK)i .<br />
Siacc CLIL palicals src frcqucatly<br />
trratrd naly evith aakylatinp aFc'at . r•ithewt<br />
ibc ennftwndinp, ctfcn~ . nf rad,.thcrary<br />
. ehi,. =rnup of paticntu ptovidc+<br />
a apcciai opponunity to uud~ tbc latc<br />
acquctac of tflleae rlrup,<br />
Patients asid Methodt<br />
We aaatysed all patients diataosed<br />
with CLlL as a 6rst primary au,eet be•<br />
twexn 1973 and 148b who Wcn reporle,d<br />
10 onc of .Sac populatioo-based ancYr<br />
.ejistries of the SEER Projram aad lrrvi.red<br />
2 a tewre wronths. Sue1 «Yiscrics<br />
tndudc albe.e in tAe raetroQoliean arem of<br />
Rasri .ad l.rwry tn• tw :: .ni .dd eLr M .<br />
Iw : . rv,TrrJ lwa• 4 . tw:<br />
1_ H t'r..:, R . k('orte. l F . Farraxi k<br />
ek(+if.. .4d..e! sy M-4ltwit+ Nnr+aa, nni-<br />
.L ., .d ('.a„ 6&t•) SSt . It F /ta.Lr. (c .,a.<br />
ti,Mn,k, litaactt. 1: .n,7lt,.a h .+r,w,• I),,n..<br />
w( ('.+cn PtmlliwM /ad ('twrotl . Mtrrut Cwerr<br />
(a.+kw ., Fktlc~d+ . MJ<br />
Wc arr "4" /n tL . l4ak IIceM tl.Ttvn .r<br />
4wra (M .. It.rbkca McKsn wW Dr . llntc. f.<br />
(.yweY l i . dau trnkv,l, to Dr.. l." idn . NeN<br />
C.t .r .w . ad 6lsrku LMw i.r a+cal re.in 1<br />
w,• sr+,+, . .eri{c a.d W, M, r„t+rt ; t'r.ra„w<br />
. .J t
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
12
Wu, A ., Henderson, B .E ., Pike, M .C ., and Yu, M .C ., "Smoking and<br />
other Risk Factors for Lung Cancer in Women," Journal of the<br />
National Cancer Institute 74(4) : 747-751, 1985 .<br />
In 1985, Wu and colleagues reported on a case-control<br />
study of women in a Los Angeles, California tumor registry . For<br />
adenocarcinoma, the authors wrote, "we did not observe any elevated<br />
risk associated with passive smoke <strong>exposure</strong> . . . at work (RR =<br />
1 .3 ; 95% CI = 0 .5-3 .3) ."<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
Smoking and Other Risk Factors for Lung Cancer In Women '-1<br />
Anne H . Wu, Ph .D ., 3 Brian E . Htndason, M .D ., 3 Malcolm C . Pike, Ph .D ., 3' and Mimi C . Yu, Ph.D . 3' ,<br />
ABSTRACT-A oas&-control study among wh+t• won»n in Los<br />
Anfl .lau County was conduct .d to inv .stipate tM rot . of tmokinp<br />
+nd othsr factors in tha etiology of <strong>lung</strong> cancyr in womirn . A total of<br />
149 pati.nts with ao.nowrcinoma (ADC) and 71 patt .nU with<br />
squamous cell urc noma (5CC) of the <strong>lung</strong> and their ap.- and<br />
sea-match .d controls were tnt*rvi.w.d Personal cigarette smoking<br />
accountrd for almost all of SCC and about halt of ADC in ttm study<br />
populat on . Among nonsmokers, slightly tlevat .d r.lat v . rtsk(s)<br />
(RR) for ADC were observed for paas vw smoke rxpoaure from<br />
spouse(s) IRR=1 .2, 95'r conf d .nce interval (CI)=0 .5 . 3,3] and at<br />
work (RR=1 .3, 95% CI=0 .5, 3 .3) Childhood pneumonia (RR=2 .7,<br />
95% Ct=1 .i . 6 7) and ch ldhood .xposura to coal burning (RR=2 .3,<br />
45% CI=1 .0 . 5 5) were add t onal risk factors for ADC, For both<br />
ADC and SCC, increased risks were assocuted w th decreased<br />
intake of S-carotsne foods but not for total preformed vitamin A<br />
foods and vitamin supplements -JNCI tpb5, 74 .747-751<br />
Lung <strong>cancer</strong> is now the fourth most common <strong>cancer</strong> in<br />
women (1) and has been projected to be the lading cause<br />
of <strong>cancer</strong> mortaliry among women by the mid•1980's (2) .<br />
Causes of <strong>lung</strong> <strong>cancer</strong>, other than cigarette smoking (3),<br />
have not been clearly identified, but associations with<br />
<strong>exposure</strong> to passive smoking (4-6), <strong>exposure</strong> to combustion<br />
products of heating and cooking fuels (7), and<br />
occupational <strong>exposure</strong>s (8-JO) have been suggested . In<br />
addition, <strong>lung</strong> "scamng" (11) and a low dietary intake of<br />
S•carotene (12-1 t) and preformed vitamin A(13-17) may<br />
increase the risk of <strong>lung</strong> eancer .<br />
This paper reports a case-control study of ADC and<br />
SCC of the <strong>lung</strong> in white females in Los Angeles County .<br />
Each of the above•mentioned factors was investigated .<br />
METHClqS<br />
Female patients diagnosed with primary ADC or SCC<br />
of the <strong>lung</strong> were prospectively identified by the CSP, the<br />
population-based tumor registry for Los Angeles County<br />
(18), between April 1, 1981, and August 31, 1982 . On the<br />
basis of information collected routinely by the CSP, we<br />
limited eligibility to white Los Angeles County residents,<br />
with no history of <strong>cancer</strong> (other than non-melanoma skin<br />
ctncer) and under age 76 at diagnosis ; we verified these<br />
variables at interview . We also excluded cases if they were<br />
born outside the United States, Canada, or Europe ; were<br />
not English•speaking ; or were not residents of Los<br />
Angeles County at the date of diagnosis .<br />
A total of 490 eligible ©ses were identified . Of these<br />
patients, 190 had died or were too ill to participate by the<br />
time we contacted their attending physician . Permission<br />
was granted to contact 272 of the remaining 300 patients .<br />
Eight patients were not located, and 44 refused to be<br />
interviewed so that we obtained completed questionnaires<br />
on 220 . On the basis of information on the CSP<br />
absuact, no significant differences were noted between<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
those interviewed and those not interviewed in terms of<br />
age, marital status, religion, and smoking status recorded<br />
on medical records . However, those who were not<br />
interviewed were more likely to have distant metastases at<br />
the time of diagnosis (58`£) compared to those who were<br />
interviewed (11%), Comparable percentages of eligible<br />
SCC (43%) and ADC (46%) patients were interviewed .<br />
We selected one individually matched neighborhood<br />
control for each interviewed case . The control had to<br />
fulfill all the criteria given above for cases (with reference<br />
date taken to be the same as that of the matching case)<br />
and, in addition, was matched with the case on date of<br />
birth (t5 yr of birth date) . Our control selection<br />
algorithm defined a specified sequence of houses to be<br />
visited in the neighborhood where the case lived at date of<br />
diagnosis . Our goal was to interview the first eligible<br />
resident in this sequence . If no one was home at the time<br />
of the visit, we left an explanatory letter and made a<br />
follow-up visit after several days . For any patient, 80<br />
housing units were visited and 3 return visits were made<br />
before failure to secure a matched control was conceded .<br />
In 150 instances the first eligible person agreed to<br />
participate, in 55 instances the second eligible control in<br />
the sequence was interviewed, and in 15 instances the<br />
third eligible control was interviewed .<br />
Cases and controls were interviewed on the telephone<br />
with the use of a structured questionnaire designed to<br />
elicit information on personal smoking habits, <strong>exposure</strong><br />
to passive tobacco smoke, <strong>lung</strong> diseases, dietary intake of<br />
vitamin A, types of heating and cooking fuels ever used,<br />
and reproductive history . We also obtained a lifetime<br />
history of all jobs (job title, activities, and <strong>exposure</strong>) of at<br />
least 6 months' duration .<br />
For childhood passive smoking <strong>exposure</strong>, we asked<br />
about the smoking habits (i .e ., amount and years of<br />
smoking) of father, mother, or other household members<br />
AtsREI'tAT1oNs USED : ADC- adenoeardnoena ; Q -eonfitlettce intenzl ;<br />
CSP-Univenity of Southern California/L,oc Angeles County Cancer<br />
Surveillance PTorram ; RRxrrlauve risk(s); SCCmtqtumous eell car•<br />
dnoma .<br />
tRereived June 11, 1984 ; revirrd Novembct 26 . 1984 ; «cepted<br />
December 11, 1984 .<br />
=5upported by grant S163 from the American Carscer Society .<br />
sDepartment of Family and Ptrverttive Medicine, Univenity of<br />
Southern Califomia School of Medicine, Parkview Medical Buildtna B,<br />
2025 Zonal Ave ., Laa Anaeles, CA 90031 .<br />
"Pruent addreu : Impetul Cancer Research Fund's Cancer Epide'<br />
mioloip Unit, Ra.dcliffe infirtnary, Oxford University, Oxford OX2<br />
6HE, Entland .<br />
s We thank the word•pro«uing pool for preparation of the manu .<br />
acip4<br />
747 JNC1 . VOL 74 . NO . 4. APiUL 1965
748 Wu, Hendet•son, P(ke, and Yu<br />
• when they lived with the respondent during her childhood<br />
and teenage years . For passive smoke <strong>exposure</strong><br />
during adult life, we asked about the smoking habits of<br />
spouse(s) and other household members when they lived<br />
with the respondent . Passive smoke <strong>exposure</strong> at work was<br />
ass-essed only in terms of the average number of hours per<br />
day to which the respondent believed she was exposed at<br />
each job .<br />
The questions on vitamin A intake specifically asked<br />
about average frequencies of consumption of 21 vegetables<br />
and fruits that are high in S-carotene and 7 foods<br />
t.hat contained preformed vitamin A during the calendar<br />
year 3 years before diagnosis of the case (19) . Pattern of<br />
use of vitamin supplements was also assessed for the<br />
same period. On the basis of U .S Department of<br />
Agriculture tables of food values for standard portion size<br />
(common household measure) of each item (20), we<br />
estimated average daily intake of 0-carotene (or vitamin<br />
A) by summing the product of the 4-carotene (or<br />
vitamin A content of each food item and its reported<br />
frequency of consumption . Quartiles of consumption<br />
were constructed on the basis of the intake pattern of the<br />
220 controls .<br />
All cases were diagnosed microscopically . Their routine<br />
pathology reports were reviewed for mention of <strong>lung</strong><br />
scarring .<br />
Statistical analysis was conducted with the use of<br />
multivariate logistic regression methods for individually<br />
matched case-control studies (21) . RR were estimated by<br />
odds ratios . A case-control pair was excluded from any<br />
given analysis if the information for either the case or the<br />
control was not known for the relevant variable(s) . Since<br />
personal smoking will often, if not always, confound<br />
other associations, RR for other factors were always given<br />
after adjustment was made for personal smoking .<br />
For ADC, RR for certain factors were given separately<br />
for nonsmokers, ex-smokers, and current smokers ; this<br />
was not done for SCC because the numbers of nonsmokers<br />
and ex-smokers were too few .<br />
RESULTS<br />
We interviewed 149 ADC and 71 SCC cases and their<br />
matched controls . The mean age at dfagrtosis was 59 .7<br />
Smoking status<br />
TAeLE 1 .-Pmwnal rnaokinp Aabite oJcaaex and coatrola<br />
years for ADC cases and 61,4 years for SCC cases . The<br />
mean ages (at date of diagnosis of the index case/ for the<br />
respective control groups were 59 .5 and 61 .1 yeais .<br />
Porsonal cigarette smoking .-For both ADC and SCC,<br />
there was a significant trend in risk associated with<br />
increasing number of cigarettes smoked per day and with<br />
decreasing age at which smoking began (table I) . Both<br />
aspects of smoking remained significant after adjustment<br />
was made for the other .<br />
Passive smoking .-Families tended to share similar<br />
smoking behavior . Controls whose father, mother. or<br />
spouse(s) smoked were more likely to smoke, to be heavN<br />
smokers, and to start at a younger age than controls<br />
whose family members did not smoke . For ADC and<br />
SCC, after adjustment was made for personal smoking<br />
habits, there were no significantly inaeased risks for<br />
having a mother, a father, or spouse(s) who smoked or fot<br />
being exposed at work (table 2) .<br />
For nonsmoking ADC cases, we did not observe an,<br />
elevated risk associated with passive smoke exposurt<br />
from either parents (RR=0 .6 ; 95% C1=0 .2, 1 .7), frorr<br />
spouse(s) (RR=1 .2; 95% C1=0.5, 3 .3), or at work<br />
(RR=l .3 ; 95% C1=0 .5, 3 .3) . Increasing RR (RR=1 .0<br />
1 .2, 2 .0) were found with increasing years (0, 1-S0, :t31<br />
of passive smoke <strong>exposure</strong> during adult life fron<br />
spouse(s) and at work, but the results were not sta<br />
tistically significant. Since the <strong>exposure</strong>s may hav :<br />
occurred concurrently, the years of <strong>exposure</strong> rtpresen<br />
units rather than chronologic time of <strong>exposure</strong> .<br />
Childhood <strong>exposure</strong>s .-For both ADC and SCC, nc<br />
significant association was found with history of luni<br />
diseases (specifinlly, asthma, bronchitis, pneumonia<br />
tuberculosis, fungal disrases, emphysema, and luni<br />
abscess) diagnosed by a physician at least 5 years befor<br />
diagnosis of the case . When the analysis was restricted v<br />
<strong>lung</strong> diseases that occurred before age 16 (childhood), ;<br />
significantly elevated RR for pneumonia was observe•<br />
for ADC after adjustment was made for personal smokin,<br />
habits (RR=2 .7 ; 95% CI=1 .1, 6 .7), and the RR for SC(<br />
(RR=2 .9 ; 95% C1=0 .5, 17 .4) was in the same directior<br />
Parental smoking did not explain this effect . Table<br />
shows that for ADC, the effect of childhood pneumoni<br />
was most apparent among nonsmokers : Of the 2<br />
ADC SCC<br />
RR 95% CI Cax/controi RR 95% Cl Casatcontrol<br />
Nonsmoker 1 .0 29/62 1 .0 2/30<br />
Ex-smoker" 1 .2 0 .6 . 2 .3 21/37 7 .7 0 .8, 70 .3 8/18<br />
,Eurrent smoker 4 .1` 2 .3 .7 .5 99/50 35 .3" 4,7 . 267 .3 61/23<br />
Current smoker : No. cit;arettes/day<br />
1-20 2 .7 1 .4 . 5 .4 38/28 17 .7 2 .3 . 138 .2 19/14<br />
?:21 6 .5" 3 .1, 13 .9 61/22 94 .4" 9 .9, 904 .6 42'9 ~<br />
Current smoker : age started to smoke . yr . ~<br />
225 1 .1 0,4 . 3 .2 8/14 7 .8 0 .8 . 73.7 6/5 ~~<br />
19-24 2 .5 1 .0 . 5 .8 22/ 15 17 .1 4 .4 . 498 .5 18; 7 l~d<br />
Smoking status<br />
TAtLE 2-Erporurr to pasrive am.okiny in eaaa and eaatrol .<br />
ADC<br />
Adjusted RR' 95% CI<br />
Mother smoked 1 .7 0 .8 . 3 .5<br />
Father smoked 1 .b 0 .7, 2 .3<br />
Snous<strong>ets</strong>) smoked' 1 .2 0 .6, 2 .5<br />
Exposure at the workplace 1 .2 0 .8, 22<br />
Lung Cancsr kt Woman 749<br />
SCC<br />
Adjusted RR' 95% CI<br />
0 .2 0 .0 . 1 .5<br />
0 .9<br />
0 .3 . 2_9<br />
1 .0 0 .1, 7 .6<br />
2 .3 0,7, 7 .9<br />
' Adjusted for number of ciaarettes smoked per day and age at starting to smoke .<br />
'W'e eliminated from the analysis 15 pairs of ADC and 4 pairs of SCC in which either the cau or the control was never married .<br />
nonsmoking ADC cases, 8 (28%) gave a history of<br />
childhood pneumonia .<br />
Elevated RR, adjusted for personal smoking habits,<br />
were observed for <strong>exposure</strong> to burning coal used for<br />
heating or cooking in a stove or fireplace during the<br />
majority of childhood and teenage years (ADC : RR=2 .3 ;<br />
95% C1=1 .0, 5 .5 . SCC : RR=1 .9 ; 95% CI=0 .5, 6 .5). For<br />
ADC, elevated RR were observed in each personal<br />
smoking habit category (table 3) .<br />
TAei.E 3 .-RR and 95% cortftdnia interinL oJADC of the<br />
tung aecording to ehildhoad pneumania and ooal burninp by<br />
personal nnokinq habiti<br />
Exposure<br />
RR (95% CI) amone:<br />
Nonsmoker Ex-smoker Current smoker<br />
Childhood<br />
pniumonia'<br />
No<br />
Yes<br />
Childhood coal<br />
burnina'<br />
1 .0<br />
3 .1 (1 .0, 9 .9)<br />
1 .4 (0 .6, 2.4)<br />
1 .5 (02, 10 .8)<br />
5 .1 (2.5, 10 .3)<br />
10 .9 (2.1, 57 .9)<br />
No<br />
Yu<br />
1 .0<br />
32 (0.9 . 11.8)<br />
1 .6 (0.6 . 3.5)<br />
4 .3 (1 .0, 17 .8)<br />
6 .3 (8.0, 13 .3)<br />
91 (2.1 . 41 .9)<br />
' Before age 16 . The analysis was based on 149 csae-control pairs<br />
of ADC .<br />
'Includes heating or cooking with coal burned in a stove or<br />
fireplace during childhood and teenage years . The analysis was<br />
based on 143 cax-control pairs of ADC .<br />
Dietary vieamin A .-Table 4 presents RR for ADC,<br />
adjusted for personal smoking habits, by quartiles of<br />
indices of vitamin A consumption . Btcause of the smaller<br />
sample size of SCC cases, the indices were dichotomized .<br />
For ADC, a significantly inQeased risk was observed only<br />
for those in the lowest quartile of {3-earotene eonsumption<br />
(4,000 IU/day), but no appretiably increased<br />
risks were observed for those in the intermediate groups .<br />
For SCC, an elevated, but not statist .ically significant, RR<br />
was observed for women with 0-nrotene intake below<br />
the median : When those in the lowest quartile of Acnrotcne<br />
consumption, i .e ., less than 2,000 IU/day, were<br />
compared to those consuming more than 2,000 IU/day,<br />
the unadjusted RR was increased to 1 .7 (from 1 .3), but<br />
after adjustment the RR was not greater than comparisons<br />
above and below the median (both RR=1 .5) .<br />
There was no association with an index of total<br />
preformed vitamin A (i .e ., dairy products, eggt, liver, and<br />
vitamin supplements) for eithez cell type . However, for<br />
ADC and SCC, an association was observed for dairy<br />
products and eggs (table 4) .<br />
Other Jactors .-We could find no association between<br />
any occupation or occupational category and risk of ADC<br />
or SCC, but there was an excess number of cooks (4 cases<br />
and 2 controls) and beauticians (8 cases and 5 controls)<br />
among cases ; both occupations have been suggested in<br />
previous studies . Elevated RR adjusted for personal<br />
TAsI-e 4,-Dietary intake of S-r.nrotent, total prrJormed tltamin A, and dairy products and eppt amoxp eaau axd coatrots<br />
Qusrtile<br />
ADC<br />
1 (high) 1.0 1.0 1-0<br />
2 0.8 0 .E, 2.0 0.6 041.4 1.7 0 .8.8.9<br />
3 1.E 0 .6, 2.7 1.1 0.6, 2-E 2.2 1.014 .8<br />
4 2.6 1 .1,5.7 12 0.6,2.8 i.7 1t,6.8<br />
8CC<br />
1and2 1.0 1.0 1 .0<br />
8 and 4 1.5 0,6, E.8 1.0 0.4, 2.4 1.6 0.7, 8.9<br />
' lncludei 21 vegetables and fruits: leafy lettuce, other leafy rreen, broccoli, carrots, tomatoes, green peaa, green beant . lima beans,<br />
asparagus, summer squash, winter sqtush, sweet potatoes and/or yams, green pepper, red pepper, hot red chili pepper, cantiloupe,<br />
watermelon, peache., apricots, n.ctarines, and tomato and/or VS juice . Analysis was baaed on 147 pain of ADC and 69 pairs of SCC .<br />
`lncludes eggs, cheeaa butter and/ar margarine, cream, milk, beef and/or calf liver, chicken and/or tvrkey liver, and vitamin supplements .<br />
' Analyais was based on 147 pairs of ADC and 71 pairs of BCC,<br />
~ Adjusted for number of cigarettes smoked per day .<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
p-Carotene' Total preformed vitamin A' Dairy products and s=trt'<br />
Adjustad RR' 95% Cl Adjusted RR` 96% CI Adjusted RRi Rilc CI<br />
JNU . VOL 74, NO. 4 . APRIL l9i5
TSO Wu, H .nd.rson, P1k ., and Yu<br />
smoking habits were observed for a history of hysterectomy<br />
(RR=1 .7 ; 95% C1=0 .9, 3 .2) and nullipariry<br />
(RR=1 .7 ; 95% CI=0 .8, 3 .7) among ADC cases and a<br />
history of miscarriage (RR=1 .5 ; 95% CI=0,5,4 .9) among<br />
SCC ases .<br />
Multiple logistic regression analysis was condutted to<br />
assess the possible confounding effects of personal<br />
smoking habits, childhood pneumonia, childhood coal<br />
burning, and S-arotene intake . The results were similar<br />
to those when each factor was adjusted for personal<br />
smoking habits alone .<br />
DISCUSSION<br />
This case-control study examined risk factors for the<br />
two main cell types of <strong>lung</strong> <strong>cancer</strong> in women-ADC and<br />
SCC . Although histologic typing was done by the<br />
individual pathologist at each participating hospital,<br />
studies comparing interobserver and intraobserver variability<br />
in classification of <strong>lung</strong> cell types reported a high<br />
concordance rate for cell types other than large cell<br />
carcinoma, which was excluded in this study (22, 23) .<br />
In this study population, about half of ADC and almost<br />
all of SCC can be attributed to personal smoking habits ;<br />
the amount smoked and the age at which smoking began<br />
were strong determinants of risk of disease . However,<br />
there are marked differences in the strength of association<br />
between smoking and cell type of <strong>lung</strong> <strong>cancer</strong>, as has<br />
been noted previously (24, 25) .<br />
The role of passive smoking in the etiology of ADC<br />
among nonsmokers is not clear . Our data are not<br />
consistent with the findings with regard to nonsmokers<br />
obtained by Hirayama (4) and Trichopoulos et al . (5)<br />
who reported a twofold to threefold increased risk due to<br />
passive smoking . However, the histology of the cases in<br />
these studies is not clear, and their data suggest that any<br />
effect of passive smoking is larger for SCC cases (5, 6) . Of<br />
our 29 nonsmoking ADC cases, 12 were bronchoalveolar<br />
cell carcinomas, and this cell type is specifically mentioned<br />
by Correa et al . (6) to have a weaker association<br />
with passive smoking . The effect of passive smoking by<br />
cell type of <strong>lung</strong> <strong>cancer</strong> needs to be investigated further in<br />
studies with much larger numbers of nonsmokers .<br />
Childhood <strong>lung</strong> disease may have a role in <strong>lung</strong> <strong>cancer</strong><br />
etiology . Certain features of the <strong>lung</strong> of a child (e .g .,<br />
susceptibility to airway closure and high peripheral<br />
resistance) might make it more vulnerable to residual<br />
abnormalities from respiratory illness (26) . This notion<br />
is supported by observations that both smokers and<br />
nonsmokers with childhood respiratory diseases have<br />
impaired <strong>lung</strong> function capacity, that their rate of decline<br />
in ventilatory function capacity with age is more rapid<br />
than that in individuals without childhood respiratory<br />
problems, and that they have higher rates of clinical<br />
diagnosis of chronic obstructive pulmonary disease (27,<br />
28) . Women with childhood respiratory problems may<br />
have incurred epithelial damage to the airway resulting<br />
in airway hyperreactivity and are more susceptible to<br />
other insults to the <strong>lung</strong> . We cannot rule out the<br />
possibility of a chance finding or of preferential recall of<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
childhood pneumonia by cases . However, our dat2<br />
appear to be internally consistent, since we found a<br />
significantly higher frequency of <strong>lung</strong> scarring mentioned<br />
in the pathology reports among cases with<br />
previous childhood pneumonia (12/30=40%) compared<br />
to those without (39/189=21%) .<br />
The associ.ation of <strong>lung</strong> <strong>cancer</strong> risk with <strong>exposure</strong> to<br />
coal heating or cooking warrants further investigationAlthough coal was identified as the major heating or<br />
cooking fuel used during childhood and teenage years of<br />
a significantly higher proportion of cases, we did not<br />
have detailed information on the years of use . Excess risks<br />
of <strong>lung</strong> <strong>cancer</strong> have been reported for coke oven workers<br />
(29, 30) and British gas workers (31) who were heavilN<br />
exposed to products of coal carbonization .<br />
Studies of men suggest that their <strong>lung</strong> <strong>cancer</strong> risk is<br />
lowered by greater dietary S-carotene (12-14, 32, 33 anc<br />
vitamin A intake (15, 17, 32, 33), but the evidence for<br />
women is less clear (12, 13, 32, 33) . We observed a<br />
significantly increased risk for ADC with the lowest leve ;<br />
of 4-carotene consumption and a similar association foi<br />
SCC . These results are consistent with findings fot<br />
females in Singapore (12) and in Japan (13), but they art<br />
not supportive of data for females in Hawaii (32) anc<br />
England (33) . Our observation of no association with ar<br />
index of total preformed vitamin A (i .e ., dairy producu<br />
eggs, liver, and vitamin supplements) and no associatior<br />
with total vitamin A intake (preformed vitamin A an(<br />
S-carotene-data not shown due to domination b,<br />
preformed vitamin A) is consistent with findings fo,<br />
females in Hawaii (32) . Conflicting findings have beer<br />
reported for subgroups of preformed vitamin A foods anc<br />
supplements . A higher consumption of liver and vitamir<br />
supplements has been reported previously for femal•<br />
cases as compared to controls, but the opposite result<br />
have been observed for males (33, 34) . Our data shor<br />
no ase-control difference in the intake pattern o<br />
vitamin supplements and a higher consumption of live<br />
among cases . Our finding of an elevated <strong>lung</strong> <strong>cancer</strong> ris<br />
associated with low levels of intake of dairy products ha<br />
not been reported for females, although similar result<br />
have been observed for males (15-17) . Our results on th<br />
role of /4-arotene and preformed vitamin A were simila<br />
for ADC and SCC, despite suggestions thai vitamin A (c<br />
rg-carotene) is more strongly protective against SCC tha<br />
against ADC (17) .<br />
Initial reports of an inverse relationship between bloo<br />
retinol levels and subsequent risk of <strong>cancer</strong> at all sites (3`<br />
36) have not been supported by recent studies (37, 38<br />
This situation emphasizes the need to reexamine even tt<br />
consistently observed association of vitamin A (or ~<br />
carotene) intake with male <strong>lung</strong> <strong>cancer</strong> .<br />
Possible sources of bias in our data must be considerr. ~<br />
Both <strong>lung</strong> <strong>cancer</strong> cases and controls were derived fro~ ~<br />
population-based samples . However, because this disea ~;<br />
is debilitating and rapidly fatal, 190 patients had died ( (4<br />
were too ill to participate by the time of initial contac ~<br />
We did not conduct proxy interviews because questiot ~<br />
on childhood <strong>exposure</strong>s and dietary history could not t<br />
assessed adeq uatel y . As ex pected , the grou p who was n ~<br />
J Na, voL.'!1 . NO . 1. APRIL tll5 ' ' ~
,.'<br />
interviewed was murr likell to have metastatic disease at<br />
diagnosis but was similar in all demographic variables<br />
measured . In addititrtt, information abstracted from<br />
medical rti-cords showed similar smoking status for those<br />
intervicwed and those nt>t interviewed . If cases who were<br />
not interviewed bccause of poor survival differed from<br />
those who survived longer and were interviewed in terms<br />
of the other risk facturs under study, this could have<br />
biased our results . However, this appears unlikely since<br />
our data showed tha( histories of childhood pneumonia<br />
and <strong>exposure</strong> to coal fires were similar among cases<br />
regardless of stage of disease at diagnosis . There is also no<br />
evidence that <strong>cancer</strong> survival is associated with dietary<br />
vitamin A intake .<br />
The etiology of 5CC can be explained almost entirely<br />
bt cigarette smoking . Cigarette smoking, however, explains<br />
only about half of the ADC cases . On the basis of<br />
this study, childhood <strong>lung</strong> disease and <strong>exposure</strong> to coal<br />
fires in childhood explain at least another 22% of ADC<br />
cases . Passive smoking and vitamin A ma}• be involved,<br />
but more research is needed to clarify their roles in <strong>lung</strong><br />
<strong>cancer</strong> etiolog} .<br />
REFERENCES<br />
(1) StU'ERaERG E Cancer sutisucs, 1982 . CA 1982, 32 :15-31,<br />
(?1 HEh'DERSOL' BE Descriptive cptdemology and geographic<br />
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ach,evcrnenu- challense-s and prospecu (or the 1980 s 'Vol I .<br />
New York : Grune, 1981 :51-69<br />
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Cancer . Washington fK: L' .S, Govt Print Off, 1982 [DHEW<br />
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(4) HtR.AYAMA T . Non•smoking wives of heavy smokers have a higher<br />
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(3) TatcHoroLLOs D, KALANDtD, A . SrARRoi L . MACMAHOn B<br />
Lung <strong>cancer</strong> and pauive smoking Int J Canca 1981 . 27 :1-4<br />
(6) CORREA P, PtCrcLE LW, Fon-ntAM E, LrN Y. HAENSUL W . Passive<br />
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(8) BRESt-oM' L, HoACUN L . RASSa,sscn G . AIRAMS HK Occupa•<br />
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(9) WYNDER EL,BESta JW .Cancerofthe<strong>lung</strong>amongnon•smokeraspecial<br />
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(1J) MErJCr HR, PI¢E MC, HENO[RSON BE, JtNG JS . Lung <strong>cancer</strong> risk<br />
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. J Natl Cancer Irut 1977t 59 :1423-1425 .<br />
1111 AutasACH 0, GAarrNVt L PAaas VR. Scu nrurr ol the <strong>lung</strong>irsaase<br />
over a 21 year period. Carscer 1979 ; 4l :656-642 .<br />
'(12) MACLENNAN R, DA COSTA J, DAY NE, LAMCH . Nc YK, SHAN .<br />
MucARATt+Aw K. Risk facton for <strong>lung</strong> <strong>cancer</strong> in Singapore<br />
Chine+e, a population with high female incidence rates . Int J<br />
Cancer 1977 ; 20 :854-864<br />
(13/ HIRAYAIAA T. Diet and <strong>cancer</strong> . Nuv CGncer 1979 ; 1 :67-81 .<br />
(le, SHExEttx RB, LErPER M, Liu S, etal . Dietary vitamin A and risk<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Lung Canc.r In Women 751<br />
of <strong>cancer</strong> in the Western Electric study Lanttr 1981 . 2<br />
1185-1190<br />
(13) B1ELS:E E . Dteun vlumin A and human <strong>lung</strong> <strong>cancer</strong> Int J Cancer<br />
1975, 15561-565<br />
(16) METTLrr. G .GRAHAM S .SkANSON M VlumtnAand<strong>lung</strong><strong>cancer</strong><br />
JNCI 1979 . 62,14l5-14S8<br />
(171 )t'ALL G . BIELKE E . GART JJ Dteury habtu and <strong>lung</strong> <strong>cancer</strong> risk<br />
Int J Cancer 1985, 51 :597-405<br />
(181 MAC.,, TM Cancer Surveillance Program in Los Angeles Counn<br />
Nail Cancer Inst Monogr 1977 ; 47 :99-101 .<br />
(19) GRAHAM S . MErruN C Fiber and other consutuenu of vegeubles<br />
in <strong>cancer</strong> eptdemtololp In Newell GR . Ellrson NM, eds<br />
Nutrition and <strong>cancer</strong> euoloin and treatment . New York . Raven<br />
Press . 1981 ;1 g9-215<br />
(20) ADAMS C. Nutriuvc value of American foods in common units<br />
L• .S Department of Agriculture Handbook No 456 Washtng~<br />
ton . DC U .S Department of Agrtculture, 1975<br />
(21) BRESLOM NE, DAV NE . Suusual methods in oncer rrsearch 1'ol<br />
I-The analvsn of case-rontrol studies IARC Set Publ 1980,<br />
52 .5-558<br />
(22) YEs!.ER R GER57 B, Al'ERLACH O . Application Of the World<br />
Health Organtnuon classifiatton of <strong>lung</strong> carcinoma to biopsy<br />
material Ann Thorac Surg 1965 . I :D3-49 .<br />
(2I! YESNER R . CARTER D Patholo=y of carcinoma o( the <strong>lung</strong> Cltn<br />
Chest Med 1982 . 5 :257-289<br />
(24) DOLL R, HILL AB . KREYaERC L The significance of cell type in<br />
relauon to the aeuolog) of <strong>lung</strong> <strong>cancer</strong>, Br J Cancer 1957,<br />
11 45-48<br />
(25) WYNnER EL . CorEY L .S<br />
. MAancHl K Lung <strong>cancer</strong> in womenPresent and future trends, J Nail Cancer Inst 1973 . 551 :391-401<br />
(26) KArrAn M Long-term sequelae of resptruory illness in infancy<br />
and childhood, Pediatr Cltn North Am 1979, 26 :525-555 .<br />
(27) BuRRows B . KNUtxor. RJ, LEaowrTz MD . The relationships of<br />
childhood respiratory illness to adult obstructive airway disease<br />
Am Rev Respir Du 1977 ; 115 :751-759,<br />
(28) SAMCT JM . TACCa IB . Srctga FE. The relauonship bccween<br />
resp,raiory itlneas in childhood and chronic airflow obsvuction<br />
in adulthood Am Rcv Respir Dts 1983 . 127 :548-525,<br />
(29) REDMOND CK, ClOCCO A, LLOYD JW, RusH HW, Long-term<br />
mortality study of steel workers, VI . Mortality from mals6nant<br />
neoplasms among coke oven workers J Occup Med 1972,<br />
14 :621-629,<br />
(30) LLOVD JN' Long-term morulsty study of steelworkers V .<br />
Resptratory oncer in coke plant worken, J Occup Med 1971 ;<br />
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(31) DoLt . R, FtsHER EJ, GAMwoN W, et al . Mortality of gvsworkers<br />
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(32) HtNrx MVW . Kot.oNEL LN, HANRtN JH . Dseury viumin A,<br />
carotene, vitamin C and risk of <strong>lung</strong> <strong>cancer</strong> in Hawaii . Am J<br />
Epidemio) 1984 ; 119 .227-237 .<br />
(3)) GRECOR A, LEE PN . RoE FJ, W1LSON MJ . MELTON A. Compari•<br />
son of dseury histories in <strong>lung</strong> <strong>cancer</strong> tsses and controls with<br />
special reierence to vitamin A . Nuer Cancer 1980 ; 2 :95-97 .<br />
(3I) Ssarnt PG, Jrca H . Cancers among users of preparatiorts contain•<br />
ing vitamin A_ Cancer 1978 ; 42:806-811 .<br />
(i3) KAR . JD, SNrTH AH, SwrTZER BR, HAwES CC Serum vitamin A<br />
(rrtinol) and carscer irscidenae in Evaru County . C,eorgia . JNCI<br />
1981 ; 66 :7-16.<br />
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risk of arscer, Lanca 1980 ; 2:813-815 .<br />
(37) Wsutrr WC, PoLk BF, UNDeaM'ooD BA, et al . Relarion of serum<br />
vitamin A and E and nrotenoids to the risk of <strong>cancer</strong> . N Engl J<br />
Med 1964, 510 :450-454 .<br />
(JF) STAHEUN HB, BUESS E . ROSEL F, WIDIitR LK, BRAIAUtER B .<br />
Vitamin A, cardiovascular risk factors, and mortality . Lancet<br />
1982, 1194-395 .<br />
JNCI . VOL 74 . NO 4, APRIL 1995
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
13
Wu-Williams, A .H ., Dai, X .D ., Blot, W ., Xu, Z .Y ., Sun, X .W ., Xiao,<br />
H .P ., Stone, B .J ., Yu, S .F ., Feng, Y .P ., Ershow, A .G ., Sun, J .,<br />
Fraumeni, J .F . and Henderson, B .E ., "Lung Cancer Among Women in<br />
North-East China," British Journal of Cancer 62 : 982-987, 1990 .<br />
A joint Chinese-American study of women in Shenyang and<br />
Harbin, two industrial cities in northeast China, reported that 228<br />
cases and 301 controls had been exposed to ETS in the workplace .<br />
A relative risk of 1 .1 (95% CI 0 .9-1 .6) was calculated, which the<br />
authors described as a "small excess risk," although it was not-<br />
statistically significant . The authors also noted that "there were<br />
no significant dose-response trends associated with years of<br />
passive smoke <strong>exposure</strong> at work ."<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf
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tna /wt disrau<br />
T+bk Vl hsu RFU ol <strong>lung</strong> noar usaeuted with tipe> ;1({<br />
pnor chroruc lunt dtseases Lung dtseases that wen fsnt<br />
durosed within thrcc mn of )unl l.aoerr dsaptotts fand a<br />
eompanble urnr penod for controlst werz rscluded from Me<br />
anal)s•s After ao)usunl for smokin=, htstory of any pnor<br />
tunt dtseau was assocuted wtth a 5d5 . tncrqsed nsk I95M,<br />
Cl E1 The excess was /reates : for prseumonta (RA<br />
: ./) An Incrcascd nsk was (ound (or broochtas and,or<br />
emphvtema . but the assoctauon was hmned to sqwmous oat<br />
;tll caneen IRR 1 6) and nol found for adenocaranoma tRR<br />
09)<br />
v.e rnvesttjated whether risk of <strong>lung</strong> <strong>cancer</strong> varied aeeard•<br />
tn/ to the fal ume following the dtarnosts of pnor <strong>lung</strong><br />
disease E.arlter drtetttoe of chrotuc bronchrtts•emphyxma<br />
conveyed rreatrr ntk Relauvt to those wrtlt no tusrory o(<br />
chrontc broncluus-emphysenu tAe RRs wers 1 .) . 1 .) . arsd<br />
I 1 respauvely for condtuons detecud 4- 10 . 11 -20, and<br />
:1 - vea .n brfort <strong>lung</strong> canm dta=rsosis On the othn hand .<br />
the FtRs wcrc hi/ner for more rseen( dtagnoses of prxumonu<br />
and TB T1x RRs wcrc :' ' 5 and I! respeetiveiy (or<br />
pnru .monia and '- 1 . 1 ), and 1 . : for TB fnt delected 4- 10 .<br />
11-20 and 2) + yean pnor lo <strong>lung</strong> aneer dtarnosu TTe<br />
tkvated nsk assocured with TB du3nox4 4-10 ye•an pnor<br />
to <strong>lung</strong> <strong>cancer</strong> was strntficant, it was obserred for both<br />
squxmous oat cell canarn and adenoarnnoma of the lunjand<br />
amon= non-smoken as well as smoken,<br />
Famil, 7rutort oJT® asd cancn<br />
we obsernd a stMhant 60' . (95',t CI 1 2-'s I i mertised<br />
nsk assocuted with TB tn a househo{d member, wttb simtiar<br />
nsks for squamous oat oell attcxn and adaooaraacvru<br />
The familial aswcunon wa.t sax m srnoken and rsoosmoken,<br />
and rrmamed unehanrrd after ad)usunl for<br />
personal history of TB TTe risk assonated w•Ith family history<br />
of TB mcrea,ised with decrrutn/ ar when the Indes<br />
subyect wu first expo+ed After ad)usttnl for smoking .<br />
<strong>exposure</strong>s at are 30 cortfernd nsks of<br />
1 .7 . 1 .5 and 1 . : whea compared to tbase with no houxhob<br />
TB czposuls<br />
Famlly history of <strong>lung</strong> as+zr in 6nt dep .c rtiatins_<br />
rrponed by 4 .5' . of the ases . wu usoeuted with a a¢uficant<br />
E0'. . (95•i. CI 1 .1-30) merusnj nsk TTM was ltttk<br />
dtf'iercecr tn nsk by cell type or erook,tnl status Tbe risk of<br />
<strong>lung</strong> eancrr was t.orne-whas hssher among thox witb a famtly<br />
htttory of other ancen tRR IA : 95% Ci 1 .0-2 .01 . wsth the<br />
esceu nsk bcinl hsther (or adenoearctaosiu (RR l .i) t3un<br />
for squa.mous .oat cell ancen (RR 1 .1) .<br />
.Nrrurnsa/ asd rtroaikrtf.r j.crnn<br />
Tabk Vlf pre+enu nats o(lua4 atncer by .atiow mensuual<br />
aad ttptoducuve f.ctott Tltre .ert littk or no assocveioa<br />
with aF at tnenarebe, parity . hrsursrtomy. tpontaateua<br />
abonion. prefnaxy rasah+z+t tn diffcult labau- assd we of<br />
oral contracrpuves There .vas a saPu5eant 30'i. (91v. Ct<br />
1 .2- 1 .1) snc7naed nsk asaoeiatad .ntb hissory ot mssa.rlude .<br />
asid ca.+es tandbd to bart a tater aF at natun .J saeoopatssac<br />
altbout.h the tr<strong>ets</strong>d .ras wt sasooth<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
Ll'NG CANCEa AMONG WOMEN IN CHINA eR!<br />
TMit Vll O eiauve nsks o( Iwy ta :cc aa.aeu .d ntk mrrauval anC<br />
reprodtcu .c facton<br />
Caafvrliv.rrr(s RR' 'I!% C1<br />
l~c ti nrnuene<br />
I/- It4t12 !0<br />
16 -1) 12' 412 1 1 101 . 1 41<br />
14-13 :15276 11101141<br />
. ) .7) SJ t3' Is 1 .f+<br />
tub .rtvlo>tr 1034) 1 .3 10.9 . t .T) 33 1 .2 33 I ./<br />
'AQ)sa•wd for yF . duesaoa . pr*>.a! *eottai aa6 sa.t1 ar .c'N..Ya af oan . .rsa<br />
faettw -Its% caa4se.ae tu .r.ah esdwrs ) A .
VGSTS 0GZOZ<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
I
t aRected itnr4eErn famly memben wu small (e*,) R .anl<br />
caw -controi studtes in Grut Antssn (Ayexb .1 .1., 19}t) W<br />
the Un ted States (Caporuo er ril., 19/9), however, sugjtu<br />
that =enettc tra,u rnay mAuentt suaeepubt)tty tn a aueabk<br />
portlon of cases Tlsese tnvrsupuons r :v-mkd s,1nll>antly<br />
tncreused nsks of <strong>lung</strong> unar assxaud wtth the reruurully<br />
controlled abthty to extensively nuubohsc the dru[ debnso-<br />
Qutrx . a tratt aRmm[ S4'i of the convol population etudtc0<br />
in the L'nned Sutes<br />
we found no strong suppo*1 for a rok o(hormoeal f.non<br />
for <strong>lung</strong> <strong>cancer</strong> overall or spectfscsJh for adenocarcraorru<br />
The cases d d tend to rs.penenec menopause at 4ter Rtes. but<br />
the trend in nsk with age at menopause wu not smooth .<br />
Htstory of prolonged labour or hysterectomy, whseh had<br />
betin suspected as nsk (acton for adenoamnonu benuY of<br />
the potential for trauma•auoctated <strong>lung</strong> embolisrn . oaurnd<br />
more frequently among our cases, but the eXCess nsks wete<br />
aot u{nfieant smce reletively frr women were alfect .d Risk<br />
of <strong>lung</strong> cancrr was recrntly reponcd to be irscrezs .d aston[<br />
Chtnese w&men ath alson nxnsvual cycle krsrth IGao r/ tl . .<br />
19bb1, but this vanable was not asxssed ia the eurrent Ftudy .<br />
In other countries thc nsk of <strong>lung</strong> canczr nrenenlly<br />
reduced amonl those with higher dKUry muke of<br />
carotenoids iZLelicr, 1999) but our 6ndmp are kaa ckar .<br />
Cases had sh=htly higher rather than lower intake of dark<br />
jreen leafN vegetables the most eommonly eonsumed rxh<br />
soura of carotene Moreover . in our arulysn uun[ a com•<br />
btned rndcs of all vt[etables nch in nrotene, high (rcquen-<br />
Rei.r..ea<br />
http://legacy.library.ucsf.edu/tid/wyk81f00/pdf<br />
AYESH, R . IDLE . 1 . RtTCHIE. I C . . CROTIiERS . MJ t HETZEL M R<br />
119tai Mrubolic oe1aauan plxnocrpes au nurkan for atarsp<br />
nbtlny to lunt canar v .rar 31L 169<br />
ptf.SLOW !+E A DAY . yE (11f01 Srorunrd MnAeLt w Cwrn<br />
RruarrA rAr .Inaltiu of Cau-Conrrs/ Srrkcs IARC Lyon<br />
CArORA54 !+E . FALK . RT . ISIAQ HJ t S orhers (Ift1) Lung<br />
tana+ nak . oaupauonal ezposure . Oebnfoqwre meubdrc<br />
phenotypt Car,rn Rn . 0 . 3675 .<br />
CHAn . w C COLIUOR!.E M 1 . FUNG, S C ! MO H C (117q1<br />
Ironcn,al anctt tn Honi Kon{ 1976- 1917 . I• J Cwrn . ?t .<br />
Iil<br />
COHE'v 11 . DIAMOND E L, GRAVE3 C.G l 1 othm 119771 A<br />
common familul component in <strong>lung</strong> oxer and ehroe+c okatrvc•<br />
tuve pulmonan dirrue la .rrr . IL 523<br />
ERSHOw A G t CHEN w K (1/9t)1 Chtn .c foa4 eornpo .oos<br />
ubks a tranatauon with EnllisA Common nama Ltun rawnvEe<br />
namaa and hnytn rortunu.d u%a .6urar»s_ fr/ C.q A.r' .<br />
(te the preu)<br />
GAO YT . ILCrT . wJ . ZHEhrG w a S ert.ers (IN7). Lwy aaW<br />
amon/ Chirxsc womrn f∎t J Cwrn . 4{ . iW<br />
GAO1' T . ILOT, w 1 .. ZHEHG, w_ 1TL.MUMEM. 1 F • HSU<br />
.aa{fa, Av, J. [{~fr . C w(Ittll Lun= ctanr ted veokia[ u Sh...f<br />
..<br />
11 . :71<br />
HINDS -4 W .4TEMMERMAKH .O .N . . YANG . H .Y a ) 9elan (IMI) .<br />
Dtffernsca r Iua1 rauoer frrsa weotny awrxi lup .a.e•<br />
Clrine+e and Hesniaan wornen n HawRii . Au. J. Cwr+.. 31 . Tt1 .<br />
KUNG . 1 . 50 K, t LAW . T . (Itfal, Lwty eRaetr t* Heuy KRy<br />
Clurses