ets exposure, lung cancer - Legacy Tobacco Documents Library

28 Mar.95 RWA/BRA C :\DATA\ETS\REGISTER .DOC 

ETS EXPOSURE, LUNG CANCER 

TABLE OF CONTENTS 

STUDY REGISTER NO . 

General Comments 1 

Brownson et al ., 1982 2 

Fontham et al ., 1991 and 1994 3 

Garfinkel e a( ., 1985 4 

Kabat and Wynder, 1984 5 

Kabat, 1990 6 

Kalandidi et al ., 1990 7 

Koo et al ., 1984 and 1987 8 

Lee et al ., 1986 9 

Shimizu et al . 1988 10 

Stockwell et al ., 1992 11 

Wu et al ., 1985 12 

Wu-Williams et al ., 1990 13 

http://legacy.library.ucsf.edu/tid/wyk81f00/pdf

PROGRAM & ABSTRACTS 

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TIIE SCIENTIFIC PRESENTATION ON EVVIRONMENTAL TOBACCO SHORE AND INDOOR AIR QUALITY 

http://legacy.library.ucsf.edu/tid/wyk81f00/pdf 

1993 . 11, 23 (~ ) 

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PROGRAM & ABSTRACTS 

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THE SCIENTIFIC PRESENTATION ON EWIRONMENTAL TOBACCO SMOKE AND INDOOR AIR QUALITY 


1993 . I1, 23 (~ ) 

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PHILIP (iIiUF: C M . D . 

THE QUESTION OF HEALTH EFFECTS OF 

EiJVIRONAIENTAL 1'OBACCO SMOKE EXPOSURE 

IN THE NONSMOKER 

Philip Witorsc,i, M .D . , FACP, FCCP 

Clinical Pro ; essor of Medicine 

Adjunct Professor of Physiology 

The George Washington University Medical Center 

Washington, D .C ., U .S .A .' 

The term "ETS" has been used interchangeably !in 

both the press and the scienti :ic literature with a variety of ~ 

other terms, such as "second hand smoke", "involuntary smoking", 

and "passive smoking ." ETS is an aged mixture of sidestream 

smoke, that produced by direct combustion of a tobacco product 

(such as the tip of a burning cigarette) , and exhaled mainstreala 

s ;,io}:e (that previously inhaled in the course of active sraoking)~ . 

The possibility that ETS may produce adverse health e"fect~ 

has generated considerable study and controversy . To~_ sn I 

Inan a,t h ; f~r~ t fi a?~z-n_F_~ n;31 . 

International Aaency for Re_s_ 

ealt 

aaencies i 

%_%==W 

a nunr p Y Y 

L 

G 

,L- ,- ~y, r,, ~ I as 

noted by the Appellate Court in a'highly publicized recent casei 

in Au,stralia between the Tobacco Institute of Australia Limite 

(TIA) and the Australian Federation of Consumer Organisations 

Inc . (AFFCO), " the cuestion whether passive smoking causes 

disease in non-smokers is a question upon which scientific 

research and discussion is continuing,'1 

Unfortunately, in many cases political, social and other 

agendas appear to have gotten in the way of objective, 

disnassionate evaluation of the science in this area . The 

purpose of this presentation is to present a critical analysis f 

the available scientific data relevant to the question of the 

possible health effects of ETS exposure in the nonsmoker . 

'The author' :, academic affiliation is listed for .tdentificatj~n 

pu :poE:os only . The views exnrese.ed here represent the perscr l 

opinions of the author and do not necessarily reflect those off flte 

universizy, any u'.:her institutions or entities with which he may ~e 

affiliated, or any sponsors of his work . 


aa-G~~ .a7r.~. . .~- o~±.a•-?- 1 dJ 

T tw t;•! l,-.lP~_ .'~ :j 

a

M 

bDjDroacbes to the Study of the Health Effects of ETS 

Three approaches have been proposed through the years for ~ 

the study of the issue of health effects of ETS, as follows : Z 

conclusions based on the chemical composition of sidestrear„ 

smoke ; 2) analogy wit .': and extrapolation from studies of tha 

health effects of active smoking ; and 3) clinical - experimenta 

and epidemiological studies that specifically address the 

possible health effects of ETS, 

it is virtually impossible and scientifically inappropriatp 

to attempt to accurately predict the health effects of ETS by the 

first approach, which addresses the potential carcinogenic, 

irritant, or physiologic effects of its•individual constituents . 

ETS is a complex mixture of chemicals and it is becoming apparelit 

from the study of the toxicology of complex mixtures that the 

effects of individual chemicals alone are not necessarily 

consistent with how they will behave in the presence of other 

substances . Furthermore, the concentrations of chemicals in ETP 

are greatly diluted as a result of their distribution in a 

relatively large but defined space (e .g ., a room), as well as 

changed chemically and physically (so-called "aging") . 

Analogies between active smoking and ETS exposure, the 

second approach, are inappropriate, not only because of the 

chemical differences between ETS and mainstream smoke, but alsc 

because the magnitude of ETS exposure is extremely low relativ i 

to smoke inhalation during active smoking . Furthermore, the 

process of inhalation of ETS is considerably different from thatt 

of active smoking . ur ;l& 

;6" 

A A 

Aa , f 

',4 `) 

0 

ith I 

T6--µ' ~ „ the only valid and concrete 

information pertaining to the issue of health effects of Ei~S hab 

been obtained from experimental and epidemiological studies . i 

~ 

~ 

ExperimentaL 

studies in hu-7-lans usually involve short-term exposure of subjec-s 

to predetermined concentrations of ETS for a defined perioa of 

time, with recording of physiological and clinical responses t6 

such exposures . These'experimental studies,* which will be 

discussed below, relate more to the acute effects of EI'S rathet~ 

than to the .r,hronic effects of such exposure . The only data 4 

available: on the cY,ronic health effacts of ETS exposure in tI e j 

nonamoke•r hava been obtained from epid?miologic studies . I 


2 

--2 l)

Epidemioloaie Methodoloay, 

Fpi.demiology involves the study of the occurrence rate off 

disease and its association wit2-h specific exposures and other 

factors in popul .ation groups . 

In the process of epidemiologic investigation, the 

researcher classifies subjects in a study according to whether ~r 

not they have a condition or disease of interest (for exaraple, ~ 

lung cancer) and according to whether or not they have been 

exposed to a factor of interest (for example, ETS) . The result!G 

of this classification are then expressed as an "odds ratio" o~ 

"relative risk", which reflects the occurrence rate of the 

disease in the exposed individual relative to the occurrence raf e 

of the disease in the nonexposed individual, 

casesS fl 

t:he 

or 

The results of all biologic studies, be they experimental ~r 

epidemiologic, are subject to considerable uncertainty, since 

variability from subject to subject is an inherent characteristuc 

of biologic processes . Furthermore, in epidemiologic studies, as 

a practical matter, only a relatively small sample of a nuch ~ 

larger population can he studied directly . Thus, the 

investigator must attempt to determine whether an observation z' ;& 

a real one (valid and reproducible on re-examination) or one du~a 

to chance variation (and not necessarily valid or reproducible)I, 

In order to assist the researcher in this determination of 

potential reproducibility, reliability and validity of the 

observations made, statistical analysis must be employed . 

Statistical analyses not only take into consideration the 

magnitude of an association but also the biologic variability 

a population relative to this association. , ! 

tl _r_p.~~•~,~ d~ 

Statistical methods in eoidemiology not only estimate odd3 

raLios but also so-called 95%, confidence intervals of the 

estir..ate of risk . The 95% confidence interval is an estiL .ate ~ f 

the variability and is expressed as a range above and below the ; 

"poinz estimate" odds ratio . The wider the interval, t :;a greal-.;-r 

the variability . If the lower boundary of the 95,1 confidenc +e 

interval exceeds unity (1 .0), the odds ratio is usually regard 

as being statistically significant, 

v a u a 

a~~dds ratio [an~ 9^`= ~- 

~ ere statistica?.Lu 

ile a stat 


3 

'~__ . 

e

k 

association between a certain exposure and a disease state ~ 

provides the researcher with some assurance that the odds ratio 

and the association are meaningful and potentially reproducible~ 

it is still an estimate with some degree of uncertainty and by r,o 

means proves that the exposure is the cauve of a par.ticular ~ 

disease . 

An added aspect of uncertainty in epidemiologic studies 

relates to the involvement of 'rconfounding variables" and other, 

sources of bias that can produce misleading results . Confoundiqg 

variables are factors, other than the exposure in question, tha~d could influence the occurrence of a disease of interest and must 

be adjusted for in the analysis . 3ê%- ;~}l-., U 4,-i k=Jn tha'' 1 

jler P i t•d ~~iri ~i nn ?rA rir gk fa .tOr5 'fbr~'anc^~2 . In O Cla~~ft7r 

the 

of 

c 

ZTS and Primarv Luna Cancer 

To date, 35 published epidemiologic reports have exanined 1the association bet,•ieen ETS exposure and primary lung cancer in ; 

the nons,ao!:er [Table 1] . These reports have described studie 's 

conducted in Asia (16 reports) ['Table 2], Europe, and the Unitea 

States . In most of these studies, nonsmoking women have been the 

subjects and spousal smoking has served as the surrogate for or ; 

marker of ETS exposure . In other words, the risk of lung cancer 

due to ETS has been based upon the occurrence rate of the diseabe 

in nonsmoking women married to smokers compared to the occurrenCe 

rate of the disease in nonsmoking women married to nons

General's Report, the 1986 U .S . National Research Council Reporr, 

and the 1992 U .S . Environmental Protection Agency Report) to the 

effect that ETS exposure is associated with a 15 - 30 % increas~d 

risk of lung cancer are based upon such meta-analyses, the 

justification for pooling the data from the various studies intcp 

a single statistical analysis and, thus, the validity of sur.h a 

conclusion, is a matter of considerable and heated debate . 

Another area of co7troversy relates to the surrogate used 

for ETS exposure, spousal smoking status . Usually, this-index f 

exposure, which is based upon the response to a questionnaire, 

lacks verification by a biologic marker, such as a specific 

tobacco constituent in a body fluid (e .g ., urine, plasma, or 

saliva levels of nicotine or its metabolite, cotinine) . 

Furthermore, spousal smoking has been shown to be an inaccurata 

estimate, both qualitatively and quantitatively, of such exposuTe 

for the following reasons : 1) it usually fails to differentiat 

between spousal smoking in and out of the home ; 2) it does not ~ 

take into consideration ETS exposure from ot'er sources (e .g ., 

social or work exposures) ; and 3) it is subject to 

misclassification of smoking status of subjects . 

With regard to ~ smoking statu~ 

misclassification, individuals married to smokers have been 

demonstrated to have an increased likelihood of being smokers 

themselves . This pher.omenon, called "marital concordance" or 

"marital aggregation", is recognized to be a potential source o~ 

inflation of the odds ratio in studies of lung cancer associateti 

with spousal smoking. ' ^

Among the potential confounders that have not been consistently~ 

considered in the relevant lung cancer - spousal smoking studieff 

are the following : 1) occupational exposures of the subject ; 2) 

other exposures of the subject (e .g ., organic solvents) ; 3) 

alcohol consumption ; 4) diet and nutrition ; 5) cooking pr.actice ; 

6) lifestyle ; 7) socioeconomic status and related issues (e .g ., 

quality of medical care, quality of outdoor air around 

residence) ; 8) genetic factors ; 9) animal exposures ; and lo) 

radiation exposure (e,g ., household radon) . Such factors could 

have a very significant inipact on the occurrence rate of lung ~ 

cancer, acting alone or in combination, and, thus, if not 

controlled or adjusted for, can result in an apparent associatic,n 

between spousal smoking and lung cancer when, in fact, there is 

no real association . 

F9'Sard the RespiratorrL System of Children 

i 

Epidemiologic studies of the association between ETS % 

exposure and the incidence of respiratory illness in children 

have been examined in two age groups, namely, pre-school childr n 

(those under 5 years of age) and older children (5 y-ears of age 

or older) . In excess of 40 such'studies have been conducted ini 

each of these age groups . Parental (usually maternal) smoking , 

has usually been the surrogate for ETS exposure in these studies . 

g`Pn s ~ c 

~r . 

i;ost studies in pre-school children have shown a generally ; 

weak but consistent association between maternal .smoking an `d 

increased incidence of respiratory symptoms and/or certain acutY 

respiratory illnesses in children . t•ihile such an association ~ 

could be due to the effects of ETS exposure, other factor is 

related to maternal smoking but distinct from ETS could explain : 

this relationship . Among these are in utero effects of active 

smoking during pregnancy and the effects of maternal smoking on, 

lactation during nursing, both of which have been addressed in i 

relatively few of the relevant studies, i= at all . in addition ; 

these studies have failed to adequately consider a variety o (f 

confounding variables, alone or in co-mbination . P_:uong these ar~ 

socio2conc,,ic status, gas stove usage, family health history I, 

subject's health history, breast feeding, use of day care, ~ 

nutritional status of the subject, quality of housing, indoor aT1d 

outdoor air pollution, and fanily size . I 

In contrast to the studies in children under 5 ye,aj~~F, of ag 

studies in children 5 years of age or older have failed to 

cqnsistently .demonstrate an association between parcnt~l ;$7okinp 

and rzspiratory he'i1'tli -effects'in cliildren . Forty-fii~e'studies~ 

in this age group indic : te that an association between matnrj ;all 

sne :,:ing and a specific respiratory symptom (cough, phlegn) or ~ 


6 

,

disease (bronchitis, pneumonia, asthma) has been confirmed no ! 

more than 50% of the time . In these studies the clinical ( 

endpoints (i .e ., the symptoms and/or diseases addressed) were I 

usually obtained from questionnaires completed by the parents and 

were conf irmed by phys ician examination or medical reccr :;s less i 

than 200 of the time . r v 

P tl ] .r °- rr .. pr:.j' .:o ..,y. . 'ja .w & j 

~ ~ 

; jj 

~ ,~,~•~dd r 

. ~i . . e ° ' As in the studies 

sof~ pre-sc o0 .1 chi r2n, these studies in older children 

inadequately considered potentially important confounding 

variables that could have influenced the outcome of a study, 

alone or in combination . 

Other Potential Health Effects of ETS 

Epidemiologic studies have also attempted to deterraine 

whether long-term exposure of adults to ETS is associated with 

adverse health effects other than lung cancer . In these studies, 

spousal smoking has usually served as the marker for ETS exposure 

(again, without biologic verification) . To date, there are no 

consistent data to indicate that•such exposures are asscciated 

with increased respiratory illness or impaired pulmonary 

function, exacerbation of the condition of individuals wi'th 

underlying lung disorders (such as emphysema or chronic 

obstructive lung disease) , increased risk of cardiovascus .ar 

disease, or increased risk of cancer at sites other than the 

luna . 

DlQ i 

en 

'~~.7_C7 " a . 

C _ 

MizMAUM- z 

Y 0 har for a def 

fi 

(1~~ 11~y ~~b0 _minl durin Whi ch tobacco smoke 

- 

i'!as uJ 

~ i~ad 

yag iah co h , i r 

e 

co a ; ~; Acute smoke e ::posurq 

evokes responses of e, .~e, nose and throat discomfort, whic : apne~z• 

to be due to direct irritative effects of components in t ::bacco~ 

sro :•ce, rather than an allergic reaction . These acute irritant 

responses, arhich are preventable by adequate ventilation (thus 

~ 

reducing levels of exposure), do not anpear to produce lc :~g-teri 

effeccs or damage organs that are irritated . 

~ I 

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11/91/93 22 :38 1 301 983 38^_S 

PHILIP 

WITCFECH . ht . D . 

WMAN_' e . Furthermore, no valid evidence existsi 

that acute ETS exposure exacerbates the condition of individual 

witri underlying coronary heart disease, and one investigator 

making such a claim has been discredited for falsification of 

data . The available scientific data also do not suppor-t an 

association between ETS exposure and harmful effects in the 

elderly or the contention that exposure of pregnant women to Ei 

adversely affects either the mother or the fetus . 

To date, approximately seven published studies have examinqd 

the acute effects of ETS exposure in asthmatic individuals, Nit 

conflicting data . While three'studies have reported no adverse 

effects, four have reported that acute US exposure precipitate 

temporary worsening of airflow obstruction on pulmonary functio 

testing in some (but not all) asthmatic subjects . These findings 

suggest that a subgroup of asthmatics may have an increased 

"sensitivity" to ETS . ì,kgi 

ncerta i n a 1 t hntirrh t rLata ._i._r.: t~a~co~_~~ 

Since it is 

known that asthma lc attacks can be precipitated by psychologic~l 

cues (e .g ., emotional factors or odors) and its uniau.e odor mak s 

it difficult to "blind" sub7ects 'to tobacco smoke ex.posure, the 

role of psychological and emotional factors in responses of 

asthratics remains to be determined . 

. 

ETS in Context - Indoor Air OualitY I 

Although ETS receives a major share of attention among 

indcor air pollutants, it is far from the only or even the raostl 

important indoor air pollutant . A number of substances pollute~ 

the indoor air that we breathe . Many of these substances have 

important potential adverse health effects, even though these 

pollutants are less readily visible or otherwise detectable than 

ETS, Some examples include nitrogen dioxide (2102) and other 

oxides of nitrogen, sulphur dioxide (S02), ozone (03), carbon 

moncxide (CQ), pathogenic and allergenic fungi, bacteria (e .g ., 

Leaicn=lla pneumophilia, the cause of Legionnaire's Disease) anc~ 

viruses, various airborne pollens, dust mites and othe Ir 

allergens, volatile organic compounds, and radon gas . Such 

substances may pose risks of health impairment that are far 

grea ;.er than any conceivably related to ETS, yet they receive 

rela :.ively scant atzenticn, in part because their presence is 

often undetected without the use of special analytical 

techniqu^s, unlike ETS, which is readily visible and has a 

distinctiva odor . 

Tt is important that ti4: issue of ETS be considered in the! ~ 

overall cot .text of these other indoor air pollutants and tha ~ G 

pot4 ~. :.iz1 h risks that to heal'- they ~ present . It is unLortunata ~ N 

that ETS often serves as a"scapegoat" for such other air ~ ~ 

pollutants, especially since measures directed at elimination of ~ 


~ 

i 

/ 

~ 

~ 

, ~

ETS, such as banning of smoking, have little to no effect on 

levels of these other pollutants or their health effects . 

Some of these other pollutants have particular relevance t 

Asia and especially Korea . A high use of automobiles, energy 

conservation measures resulting in "tight", poorly ventilated 

buildings, and the utilization of relatively polluting fuels ha e 

contributed to making the indoor air in many Asian cities, ~ 

including a number of Korean cities, highly polluted . Thus, fo 

example, studies in 1990 demonstrated that the mean sulphur 

dioxide level in Seoul and several other Korean industrial 

centers exceeded the applicable environmental standard, i .e ., t e 

recommended safe exposure level . 

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recently, studies done in Seoul by Kim and associates have 

demonstrated higher indoor than outdoor levels of not only carbbn 

monoxide, but nitrogen dioxide and formaldehyde as well, largely 

attributable to indoor cocking and heating, coupled with poo Ir 

ventilation . These studies have also demonstrated that selected 

homes in Seoul have significantly elevated levels of radon, a~ 

naturally occurring radioactive gas that is a potentially 

important cause of lung cancer . I 

Conclusions 

our analysis of the data reveals that there is little to n~o 

good evidence that chronic exposure to ETS is a health risk to I 

adult individuals . While parental smoking appears to be f 

associated with an increased incidence of acute respira-,-)r !'y 

illness in pre-school children, no such finding or imoai-r-,ent c ;f 

pulmonary function is consistently evident in school-age or oldI ~ar 

children . The role of confounding variables and other factors,~ 

such as in utero effects of smoking during pregnancy, family 

health history, and breast feeding, alone or in combination, on 

the apparent association between parental smoking and r=_spiratc~ry 

illness in young children remains to be elucidated . Althougtl 

acute ETS exposure may produce eye, nose and throat irrication~in 

a concentration-related fashion, there is little to no 

that it results in adverse lower respiratory or cardiovascular ( 

:~ F .~ 'T ;i~ 


9

11/01/93 22 :39 1 301 983 38?8 FriILIF WITuFSVH, M .D . F'~~Z_ c li 

responses in healthy individuals . While acute ETS exposure may 

evoke respiratory responses in a subset of asthmatic individuals, 

a psychogenic basis for such responses has yet to be ruled out . 

As indicated earlier in this presentation, the issue of 

health effects of ETS has been examined by several scientific 

groups and has lead to reports . Several of these reports hae 

stated that ETS exposure is a health risk, with particular 

emphasis placed on risk of lung cancer in the nonsmoker and acu~e 

respiratory illness and impaired lung function and growth in 

children . The most recent report that has arrived at such 

conclusions is the 1992 U .S . Environmental Protection Agency 

(EP.A) Report on the Respiratory Health Effects of Passive 

Sraoking . 

How can one reconcile our conclusions with those arrived a 

by the EPA? To be frank, our analysis is more comprehensive, 

more thorough, and more balanced than that appearing in the EPA 

report . A review of that report will reveal inconsistencies in 

and disparities between the data reviewed and the conclusions 

implied or stated in the body of the report, as well as those 

implied or conveyed to the press•. It is evident from the ways 'n 

which data have been manipulated, explained away, or-interprete by the EPA, and the way in which dissenting opinions have been 

addressed, that there is in the EPA Report an unclear separatioll 

of objective science from political, social or other agendas, o 

preconceived notions. is, 

It is important that the issue of ETS be viewed in the 

context of indoor air pollution in general . One must keep in 

mind the fact that a number of less visible indoor air pollutan,`Ls 

present a much more significant health hazard than ETS, even 

though the latter attracts considerably more attention and 

emotion than the former . 


10

I 

11/01/93 22 :38 1 301 983 3829 PHILIP WITORSCH, M .D. PAuE 16 

TABLE 2 . STUDIES OF SPOUSAL SMoKIHG AND RISK OF LUPiG CANCER - 

ASIAN STUDIES 


15 

7 . . 

~ 

~ 

~ 

~ 

~ 

~ 

~ 

~ 

W

i]./01/93 22 :38 1 301 983 3928 PHILIP WITORSCH, M .D . 

S-= 

1 . CHAN 1982 

~. T-IRAYAMA 1984 

3, LAM 1 985I88 

4 . IVL1 1985 

5 . A.KIBA 1986 

6. GAO 1987 

7 . KOO 1987 

8, LAM19 7 

LIE-LgLIM 

10 . INOUE 1988 

11 . KATADA 1988 

12 . SI-MIIZU 1988 

13 . L :[ 1989 

14 . SOBUE 1990 

15 . 1iE/LIU 199•0/91 

HE 

0.75 

1 .20 

1.,52 

1 .19 

1 .55 

2.55 

8 .41 

1 .10 

1 .01 

1 .13 

0.77 

16 . NVU-WI•LLIAIITS 1990 0 .70 


-4 °i! Fl'l ! .T : :'i~ 

I0KINt'x AND LU?~I(t~r, ER 

95% 

0.43, 1 .30 

1 .252 .11. 

1.02 ; 3,71 

0 .60, 2 .50 

0 .88, 2 .63 

0 .82, 1 .73 

0 .90, 2 .67 

1,165 2 .35 

n 4,29 

0 .74, 8 .78 

0 .81, 86 .84 

0 .65, 1 .85 

0 .69, 1 .48 

0 .78, 1 .63 

0 .30, 1 .96 

0 .60, 0 .9-0 

PAGE 17


2025®51395

~ 11/01/93 22 :38 I 301 983 3828 PHILIP WITCRSCH, M .D . 

A,SIAIl STTM+QFBPUUS T 9MOK7N+Cx AND LUN- G CANGER 

S-1I ER 915% C .r, 

1 . CHAN 1982 0 .75 0 .43, 1 .30 

Z, H~YAMA, 1984 LJ63 1 .2 2 .11 

3 LAM , 1985188 '2 .~.. 

, .OI 

1.0 71 

4 ." 1985 1 .20 0 .60, 2 .50 

5. AKIBA 1986 1 .52 0 .88, 2 .63 

6. GAO 1987 1 .19 0 .82, 1 .73 

7 . KOG 1987 1..55 0 .90, 2 .67 

$, LA.I4i 19 7 1 .65 1 _2,35 

L-Gha . . = 2 .16 0 4,29 

10. INGUE 1988 2 .55 0.74, 8 .78 

11 . KATADA 1988 8 .41 0 .81, 86 .84 

12. SIBIV.IIZU 1988 1 .10 0 .65, 1 .85 

13 . LI 1989 1 .01 0 .69, 1 .48 

14 . SOBUE 1990 1 .13 0 .78, 1 .63 

15 . IiE/LIU 1990/91 

0 .77 0.30 , 1 .96 

16 . 1V'(J-ZVILLIA.MS 1990 0 .70 0.60, 0 .90 

'.L P1'1 ':T'G 4'.= .~11 „h 


PAGE 17 

~ 

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11/01/93 22 :38 1 301 983 3828 PHILIP WITORSCH, M .D. PAuE 14 

TABLE 1 . STUDIES OF SPOUSAL SMOKIPtG AND RISK OF LUNG CANCER ° 

WORLDWIDE STUDXES 


~ 

~ 

~ 

~ 

~ 

~ 

~ 

~ 

~ 

13 ~

11/01/93 22 :38 1 301 983 3828 PHILIP WITORSCH, M .D. PAGE 15 

$ I2Y na Pas c .I . 

1 . CiARFIKAEL 1981 1 .18 0 .90, 1 .54 

2 . CHIIM 1982 0 .75 0,43, 1 .30 

3_, TRTCRO?OYJLO9 1983 2 .13 y .19, .4 .Z2 

..., . . . .., ~.~ 

4, CoktRL"A 1983 2 .07 0 .82, 5 .25 

5 . AA}3AT 1984 0 .79 0 .25, 2 .45 

6 . av7rFLER 1984 0,81 0 .34, 1 .90 

7 . I3I7 :.LI8/St11.8; 1984/89 1 .00 0,20, 4 .91 

S . MIWIYAMA 1984 1 .63 1 .25 

9 . f3AItF I NAEL 1985 1 .31 0 .87, 1 .98 

10 .~LAM85/118 

;-01 

1 .09, 3 .71 

11, FiU 1985 1 .20 0 .60, Z :50 

12 . ARIBA 1986 1 .52 0 .88, 2 .63 

13 . LEE, 1986 1 .00 0 .37, 2,71 

14 . 9ROWNSON 1987 1 .52 0 .39, 5 .99 

15 . GAO 1987 1 .19 0 .82, .1 .73 

16 . HUMHLB 1987 1 .70 0 .60, 4 .30 

17 . KOO 1987 1 .55 0 .90, 2 .67 

1, ,8,,. LRM 1987 1 .65 1 .16, 2 .35 

19 . PFsRSH.AC3E'N 1987 1 .28 0 .76, 2 .15 

20 . V.MRELA/JANcRICH 87/90 0 .94 0,76, 1 .17 

21 . GENG 1988 2 .16 1 .0 ~ 8 ; 4 .29 

72 . INOUE 1988 2 .55 

0 .74, 8 .78 

23 . K.riTADA 1988 8 .41 0 .81, 86 .84 

24 . SHIMIZU 1988 1 .10 0 .65, 1 .85 

25 . BUTZ.ER 1988 2 .02 0 .48, 8 .53 

26, LI 1989 1 .01 0 .69, 1 .48 

27 . 3VEN3SON 1989 1 .26 0 .57, 2 .82 

28 . SOBUE 1990 . 1 .13 0 .78, 1 .63 

29 . HE/LIU 1990/91 0 .77 0 .30, 1 .96 

30 . KA.HAT 1990 0 .90 0 .46, 1 .76 G 

31 . KALANDIDI 1990 2 .11 1 .49 , 4 . 08 

~ 

LZ 

32 . WU-WILLIADfs 1990 0,70 0 .60, 0 .90 

® 

~ 

33 . FONTftAM 1991 

M 

1 .29 0 .99 , 1 . 69 

~ 

~ 

34, BROht:15oN 1992 1,00 0 .80, 1 .20 Lo 

00 

35 . 6TOCF;WELL 1992 1 .60 0 .80, 3 .00 


~

ItLGUt .wT0ttY TOxtO01aGY Ar+D ?IiwlwAcotlxtY 19, 309-316 (1994) 

lncanslstency between Workplace and Spousai Studles 

of Environmental Tobacco Smoke and Lung Cancer' 

IvSAUR1CL• E. LL•VO1S" AND MAXWELL W. LAYARDt 

'F.nriroemental Nrahh Re .rourcrr, Ttbu,on . Calijornla 94970~ and tLayard .lrsoclates, 

Alomrda, Ca!(/ornia 94301 

Itccefvcrf January 10. 199! 

!n a t'isk astessment ssteased at thc end o( 1992, thc U .S . Environmental Protcetion A ;cncy 

(EPA)condudeG that environmental lobacea smokc (ETS) Is a known hunu,n lung urdnotea . 

The A=ency re.ached that eondusion primarily on the buis of epidcmiolo5ie nudtee of self .rsponed 

nevcr•smokin; women, in which the ext>o:ure index was marriagc to a smokcL llowvver, the tuc 

of the spousel smoking expoaure surmpate introduces many potcntiat wn(oundinR fseton . Such 

confoundins and bias due to denial of activc smokin6 art likely aplanations for weak and in• 

consistent rer»nod L•TS-lunz csncer assnciasions . This contention is tupponed by the ruults of 

1A wortdvdde studies of lunl pnetr and ETS exposure in the workplacc . which in wmbination 

indiuted oo risk elcvation . Wnrkplaoe ETS-luaS uncct• studics are not subjoct to the bias and 

confounding intsoduaed by the spousal smoking exposutt surrosate. The t:PA Ignored thc workplacc 

studies ln its risk auesamont and eatrapolatad the resulu of orwtsaal smoking nudiet to 

workplxx and other sourtrt of LT'S exposurt : In its enimate of ETS•ataributable luna< cancer 

deaths in the Unitod Sutes, the EPA asc :ihed over 70% o(thc deaths to nonspousal 1Ì'S c~+osurt :, 

primarily workplaee ezpocure, Considcrt:d in their entirety, she ETS-lung cancer enidenioloaic 

data do not suppon a uusal infcratea or provide a tcientihc boais for sovernmcnt reSulation of 

smotiing in the workptace. o t»r Aols.mK t•rWl, tr.r . 

1 . INTRODUCTION 

The U .S . Environrucntal Protection Agency (i=.PA) recently issucd a risk assessment 

of lung eanccr tnonality and environmental tobacco smoke (ETS) exposure (U .S . 

EPA, 1992) . Tlte EPA report calculated a sumtnnry relative risk oC 1 .19 (909'o confidence 

interval, 1 .04-1 .35) from a meta-analysis of results of 11 U .S . studies (9 csse-cantrol 

studics and 2 cohort studies) of reportedly never-smoking female subjects. (In a depnrture 

from conventional prnetice, the EPA citcd 90% confidcnca intervals for reJativc 

risks, on the basis that they corresponded to one•tailed 5% sSgnificance tesu ; a 95% 

con5dence interval for the summary rclativc risk is 1 .02-1 .39 .) These studics used 

t This work was supported in pan by Thc Tobaero Institutc . The vic-x expressed rrprncnt the pcrsonal 

opinioas of the euthon and are not neaessariiy those o(Ths Tobacco lnstitutc, 

0273-23W/94 T6.00 

'~ c- .>fiv, o 1914 !., kninls h.c. uc, 

.v ris)"I .rnvud-,:.- u ..r r6 .. ,Ma..,c 


309


310 I,F.VOIS AND UYAftU 

marriagc to a smoker as the b`TS exposure indgx . The resulu of each study were 

adjusted for smoking status misclassification-currtat or exsmoketa falsely declaring 

themsalves to be never-smokcrs-betorc bcing comhined in th : rnetn•analysis . An 

adjustment for background exposure (exposure from soutYxs other than the spouse) 

increased the summary rclativc risk to 1 .59 (95% confidencc interval, 1 .02-2.90) . The 

relative risk from bttckground ETS exposurc for women married to nonsmokers w-.u 

estimsted to be 1 .34 (95% confidencc interval, 1 .01-2 .08) . On the basis of the U .S . 

relativc risk estimate of 1 .19 before background adjustment, which was judged to be 

statisticafly significant, ond on the basis of the rosults of foreign studies as well as 

consideration ofthe biological plausibility of the association, the EPA repon concluded 

that there was sufficicnt evidcnce from human studies to ciassify F.'rS as a Group A 

(knawn humtin) carcinogen in terms of the EPA Guidelines for Cnrcinogen Risk 

Assessment (U .S . EPA, 19$6) . 

However, there are problems with the k.PA's risk determination . Its meta-analysis 

of U .S . studies omitted two studies which were published before the EPA document 

was rcleased ; Brownson et u! . (199' Z) and Stockwcll er ul . (1992) . Using the L'?A's 

methods and assumptions, we have calculated a summary relative risk of 1 .07 from 

a mera-analysis of 13 U .S . female spousal smoking studies, including these two recent 

studies . This relative risk, with 95% conticJence intt :rval of0 .95-1 .21, is not atatistically 

significant. Furthermure, iheru is a highly significant (P < 0 .001) inconsistency between 

the summary relative risks for six country-specific groups of female spousal smoking 

studies considered by the EPA (Table 1) . Thcse relative risks sre all either only wcakly 

clevated or, in the atsz of China, below 1,0 . In Section 2 we point out that e likely 

explanation for this geographic inconsistency is bias and confounding introduced by 

using spousal smoking as an exposurt surrogate . In Section 3 we cxaminc the epidemiologic 

data on workplace ETS exposure, which were ignored by the EPA but which 

overall exhibit no risk elevation . The inconsistency between the spousul and workplace 

studies supports the hypothesis that small risk elevations rcponed in some spousal 

studies are due to uncontrolled bias and confounding . 

2. BIAS ARISING FROM "I'fiE SPOUSAL SMOKING STUDY DES(GN 

Grcc= 2 .01 1 .33 3 .04 

Honj Kont 1 .49 1 .16 1 .88 

lapan 1 .42 1 .15 1 .75 

Western Europc 1,16 0,7E 1 .73 

United States 1 .07 0 .95 1 .21 

China 0 .34 0 .71 1 .00 

Wii ST :ZB--`t66i'TZjSLL :-v6biSjb E) A='MIX01 NI S1N01'T1SNO :) 

r 

: 

non< 

evitl : 

ine .>r 

A 

:LtT o: 

1 ;10r 

nftL 

smus 

be~ ;, 

ciatic 

in frL 

cou ; 

rc c . 

ofe : 

sn•,c 

Stcr 

an c! 

spou 

evar• 

clcri~ 

a~cr 

A 

thru 

tobe 

13eca 

c : nc 

in sG 

clas` 

was . 

et a/ 

The only explanntion offered by the EPA report for the geographic inconsistency a 2 . : 

in the spousal smoking studies was that it could he due to d'tffcrences in the intensity is qt 

of spousal exposure between countrics or to diffrrcnces in the ratio of spousal to nte . 

0 .89 

et a, 

TARLE I 

misc 

MezA•AN&I.YSCS 6(' SKUtsAL St.tORtNG CrtoYMiotAGiC SttJUtES 

clmc 

fo rr i 

Country Rclntivc risk 95% Cnn6dcnco intcrra7 O coul 

N ~ relnt A 

tion . 

~ dosc : 

~ ing- 

~'°~ rclat

SlS 

:nt 

\ 's 

I m 

:nt 

:y 

ty 

tn 

M 


.' EAlv1RbNMENTAL TU}tACxO ShtOKE AND LUNG CANCF .R 311 

nonspousal ETS cxposurc . Nowevcr, these ideas wcrc not supported by any hard 

evidence, and no credible dil ;erc:nces in Fl'S exposure patterns eould explain the 

inconsistency (Layard, ) 992) . 

A more likely explanation for the gcographic inconsistency is that the reported 

associations are the product of uncontrolled bias and confounding linked with spousal 

smoking status and opcntinz in varying degrees in different countries . Spctusal smoking 

ic a proxy, or indirect measure of actual ETS exposure, and its use introduces a host 

of concordant exposures, many of which are potcntial confounders ofreponed spousal 

smoking-lung catteer associations . Spouses sharc many imponant environmental and 

bchavioral risk factors that are likely to confound a reported L i S-lung cancer associntion 

. For example, sntokcrs and thcir spouscs have bccn shown to have dieta lower 

in fruiu and vcgctahlcs, and higher in fat and alcohol consumption, than nonsmoking 

couples (Friedman er al ., 1983 ; Koo ct al . . 1998 ; Lc Marcltand ct al., 1991 ; Shibata 

ur al., 1992 ; Sidney cL al . . 1989 ; Thompson and Warburton, 1993). The magnitude 

of dietary confounding is thought to be at (cast as largc as thc reported U .S . spousal 

stnoking-lung eanccr association (Le Marchand cy al . . 1991 ; Shibata er al., 1992 ; 

Sidney et al ., 1989). Other lung cancer risk factors such as lack of excrcise and low 

suciocconomic status (which involves such things as occupation, living condit ;ons, 

and quality of hcalth care) atr more common among self-reported never-smoking 

spouses ofsmokcrs than among never-smoking spousc .c of nonsmokers. In fact, nearly 

every potential confounder that has been identified is likely to inflate a risk estimate 

derived from spousal smoking data . None of the L•'1'S-lung cancer epidcmiologic studies 

adequately accounts for the eflccts or most or the known potential confoundcrs . 

As wcll aa being cottfoundcd hy numerous lung cancer risk factors introduced 

through spousal concordancc, the spousal smoking study design is generally agreed 

to be biased by the misclassification of some current and exsmokers as never•smoken . 

13ecause spouses or smokers are more likely to be smokers themselves than spouses 

of nonsmokers, denial of smoking is likely to upwardly bias lung cancer relative risks 

in spousal smoking studics . The EP/+ made some adjustment for smoking status misclassification, 

but it is doubtful whether the adjustment for the U .S . female studies 

was adequatc, in the light of available information on misclassification rates (KJesgcs 

et al., 1992 ; Lee, 1992; Pcrez-Stable et al ., 1992 ; %genknccht et al., 1992) . Assuming 

a 2 .5% misclassification rate of U .S . female current smokers as never-smokers, which 

is quite r„otuistent with avaiiablc data, instead or the F :PA's assumption of a 1 .09% 

rate, produces a summary relative risk estimaic of 1 .00 (95% confidence interval, 

0 .89-1 .14) from 13 U .S . studics includinz the Rn>wnson c.t a1. (1992) and StocScwcll 

e: al. (1992) studics-that is, no risk elevation . Little or no data arc availablc bn 

misclattification rates in foreign countries . Tlu EPA's as .aumptions about foreign misclassifiwtion 

rates resulted in minuscule or no adjusunent to the relative risks of 

foreign studies and could be quite erroneous . Smoking status misclassification, then, 

could be another source of tcographic inconsistency in the spousal smoking studies . 

Although somc of the spousal smoking-lung cancer studies reported dose-rrsponse 

relationships, the interpretation and importance of the doso-response data arc qurstionablc 

. '('hese data lack consistency between studies, and within studies for different 

dosc indicrs Most important, many potential confounders of reportcd spousal smoking-lung 

cancer tssociations, as well as stnoking ttatus misclassi5retion bias, are correlated 

wit0 spousal smoking in a dose-dependcnt fashion (Friedman ct al ., 1983 ; Koo 

0


312 . LL•VOfS AND t.+.YARt) 

er al., 1988 ; Lc Marchand c1 al., 1991), and such corrclations could account for appareuc 

dose-responsc trends . 

As part of its justiflcation for concluding thrt ETS should be classificd as a Group 

A careinogen, the EPA claimed that the proportion of spousal smoking studies reporting 

a lung cancer risk elevation is improbably high and cannot be attributed to chance 

alone. However, this argument is meaningless, since it depends on the dubious assumption 

that the spousat smokinZ study design is essentially free of uncontrolled 

influences, and produces att unbiased estimate of an ETS effcc :t . The opposite assutnption, 

that the spousal smoking design is subject to positive bias and confounding, 

is more likely to be true, so weak spousal smoking-lung cancer risk elevations in the 

individual studies may well be the result of anifact alotte . Givcn the large number oi' 

studies, all using the llawcd spousal smoking study design, a statistical u :sl of association 

based on the proportion of positive studies will with high probability detect the influcncc 

of bias and confounding inherent in that design ; that is, such a test will likciy be 

significant simply due to anifact . 

3. WORKPLACE ETS-1 .UNG CANCER STUDIES 

Having estimated an ETS-lung cancer risk from fcmale spousal smoking studies, 

the EPA extrapolated that risk to males, to exsmokers, and to workplace and other 

nonspousal. ETS exposure. A suhstantial majority of thc EPA's estimatcd ETS-attributable 

annual U .S . lung cancer deaths, 2200 of 30G0 total deaths (71 .9So), were ascribed 

to nonspousat exposure sources, primarily workplace ETS exposurc . Rcmarkably, the 

EPA did not use available information front nine U .S, studies of workplace ETS 

exposure to estimate workplacc ETS-lung canccr risk . Instead, the agency axsumcd 

that workplace l3TS risk can be axtrapolated from the spousal risk estimate . 

However, a comparison bctwcen the workplace BTS-lung cancer dttta and the 

spousal smoking data indicates that the workplacc data are not consistent with even 

the weak risk elevations roponed iu some spousal smoking studies, and indeed the 

combined workplacc studies exhibit no ETS-lung cancer association . 

To make this comparison, we performed, using the summarization method employed 

by the EPA, a meta-analysis of the rt,-sults of 12 studies that have reportcd lutts 

caneer relative risks for workplace exposure to L•-1'S (Table 2) . In most of these studies 

the exposure index was sclf-reponed exposure to ETS at work, and the comparison 

group was porsons not exposed at work . Of the 12 studies, 7 were conducted in the 

United States, 3 in Asia, and 2 in Europe . L•levcn studies, including 6 U .S . studies, 

reported results for women, 4 studies, including 3 U .S . studies, reportcd results for 

men, and one U .S . study rcported results for rncn and women combined . Reported 

sex-specific relative risks ranged from 0 .68 to 3 .27, with 9 of 16 being above 1 .0 and 

the remaining 7 being 1 .0 or bclow . The authors of two U .S . femalc studies, IIrownson 

er al. (1992) and Stockwell er aL (1992), considered workplace ETS oxposure and 

reported no sigtti6cant increase in lung cancer risk, but did not present numerical 

results . Of the 16 reponed relative risks, we combined 15 by computing a weighted 

average of their logarithms, the wcights being the inverses of the variances of the log 

relative risks (the Butler rclutive risk of 0 .0 for males could not be ittcludcd in the 

mcta-analysir). The sunttnary relative risk for 12 of the 14 worldwide studies was 1 .01, 

with 95% confidence interval (0 .92, 1 .11) . The summary rr,.lative risk for 7 of the 9

Fontham rc mJ. (199I) 

Gas6nkd d d. (1983) 

Jancrich d at (199(l) 

Kabal aal Wwdv (1934) 

Kab .t(1990) 

Kalaodidi d d. (1990) 

Koo cl al. (1954) 

Lae e e/. (1986) 

Slamizu d o). (1983) 

Stock.rcU ct uL (1992) 

Wu e cL (1955) 

iVu•WdGamf d ol. (1990) 

Comparison jnwp 

Not exposcd at +rork 

F Workod with smokn for 1l+ years /vcvff workod .rith a smokcr 

M Worked with rmokcr for 1 t+ years T:cvrswwkcd wilh a smoker 

F E•cr exposed .t .wrk Ncrcr esporad at work 

F Exposed at work in pasl 25 years Not apowd anywhere in past 25 ycars 

F d M 150 paw.-ycarY' of workplaoc ocpoaurt No history of workplace capowre 

F Raufulr exposed .t work Not rcqularly cxpor«f at wvrk 

1,4 Rctulartp capo.xd at .+rork Not rcTulady cnposal at wvrk 

F Evcr cxpoad at work Ne .a espoa,d at work 

M Evcr exposed at work Nercr ctpoaal at .•ork 

F Exposed at work Not employed 

F Exposed at work only or at home and at work Not exposed al home or at work 

F ERpt»al at .rork Not caposod at work 

M Exposed at .rosk Not uposed al .•o+k 

F Someone al wotkplaoc snmka No one at .otkpiacc srnokcs, or 

su bjcct does not .ror k 

F Exposal at .rork No homc or .vork c.lwmnt 

F Extwwd .t nak Not expoxd at wotk 

F Ettporod .rt vrork Not exposed at wotk 

tn tcncril, no drntcd lunt 

pnccr risk »ociatod aitk 

ETS acpcmnc in the 

workplace 

1 .47 

0 .0 

0 .15. 14 .06 

1 .74 1 .03 . 1 .73 

0.93 0 .73 . 1 .13 

091 0 .60 . 104 

068 0 .32, 1 .47 

3 .27 1 .01, 10.61 

1 .00 0.49, 2 .06 

0.96 

0 .46, 2_10 

1 .39 0 .76 . 2 .54 

1_36 0.50, ) .73 

0.61 0.17 .2_33 

161 0.39, 6.60 

1_20 0.69, 2 .01 

No si6ni6nnl Sncmuc in risk for 

Norkplacc exposure 

' 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_ 


1.3 0.5 .3 .3 

1.1 0.9 . 1 .6 

w


314 ~ lrvots nrdu 1AYAnn 

U .S. studies was 0 .98 with 95''ro confidencc interval (0 .89, 1 .09) . Although we could 

not include the Arownsou ci al . (1992) and Stockwcil rr al . (1992) studies in the mctaanalyscs, 

since they did not report relative risk esumatrs for workplacc exposure, the 

authors' cotnutents, noted iu Tablc 2, indicate tha : including them would not change 

the conclusion that there is no epidetniologic evidence of an association between 

workplace ETS exposure and lung catlcer . 

In most of these studies, the referencc "nonexposed" group consisted of subjects 

who reportedly were not exposed to ETS at work, but may have b .:ccn czposed clsrwhere, 

such as in the homc . Subjects in the workplacc•cxposed group also may have been 

exposed to ETS elsewluru. 1f there werc an GTS-Jung eancer association, camParison 

betwecn these groups would tcnd to produce lower reported relative risks for F."15 

• workplace exposurc than would a comparison between groups having no natworkplace 

ETS exposure. Howcver, ttonoccuPational ETS exposure could not climittate the cffect 

of workplace exposure if a real association existed, so tlu combined results of the 12 

studies, showing no lung cancer risk elevation, stand as cvidcnce against tlte existence 

of a link between lung cattcer risk and E7S exposure . 

The fact that, with the cxccption of Chiua, summary relative risks from spousal 

stnoking lung cancer studies are higher than that from -orkplace ETS studies suppoRs 

the arguments of Section 2 that tlu rcponed spousal smoking risk elevation is a con• 

sequcnce of bins and confounding factors that are introduced by the spousal smoking 

study design . Workplace studies would not be subjeet to bias and confounding due to 

spousal concordance, and this is a likely explanation for the inconsistency between 

workplace and spousal smoking findings . 

The EPA (Farland, 1993) took the position that workplacc L•TS studies ean be 

disregarded for several reasons: (1) thcre arc fewer worldwidc workplace studies than 

spousal ETS exposure studies ; (2) workplaco exposures arc much more variable over 

time than spousal cxposures, sinee study subjects and their co-wurkers typic :ally changc 

jobs severnl times during a lifetime, while ETS exposure fratU spousal smoking is 

relatively stable over time ; (3) presence of ha :e.ardous chemicals in somc workplaces 

can make interpretation of study results lnorc difficult than for spousal studics ; and 

(4) it can be inferred that if home b?S exposure can cause lung cancer, exposure "at 

comparable levels from other sources" can also incrcasc risk . These arguments do not 

withstand close examination . Iirst, 14 workplace E'i'S studies comprise an important, 

and relatively large, database that cannot be ignored . Second, the notion that workplace 

rTS exposures are much more variable than "relativcly stable" spousal exposures is 

unsupported spcculatiotl, In fact, the opposite may well be the case : it is hardly uncommon 

for people's smokius habits to change and for cohabiting partners to change, 

while there is no particular reason to suppose that subjects' workplace ETS exposure 

would be markedly difCerent even if they changed jobs, particularly since the type of 

job and work environtnent are likely to be similar . Third, the proportion of subjccu 

in the workplace ETS studies who arc exposed to occupational lung carcinogens is 

likely to bc quite small, since 111c studies arc population-bascd, so it is hard to understand 

how workplaae ehcmicals could substantially bias an ETS-lung cancer association in 

these studics. In any case, if there wcrz such a bias, it %++ould surely tend to inflate an 

observed ETS risk, rather than tlu opposite . One would expcct smoking prevalences 

to be higher, not lower, in hazardous workplaces than in others since such vvorkplaces 

tend to employ bluc.collar workers . The I:PA's fourth point, that ETS exposure in 

workplaces is comparable to home exposure, and therefore if home exposurc can 

I 

I

could 

metart:, 

the 

:hange 

;tween 

ibjects 

wh ere, 

e bccn 

t ~>on 

Ir LTS 

•kplace 

; effect 

the 12 

;stcncc 

pousal 

pporu 

acontoking 

ie to 

~een 

:an be 

x than 

e over 

:hange 

ting is 

places 

~' ind 

t, "at 

do not 

)rtant, 

kplace 

ures is 

ly untange, 

)osure 

ype of 

.bj ects 

ens is 

ztand 

ion in 

ite an 

:ences 

;laees 

ire in 

can 

M 

ENVIRONML•hTAL TODACCO SMOKE AND 1,UNG CANCER 315 

cause lung cancer, so can workplace exposum, is not an arbument for dismissing tFte 

workplaec cpidcrniology at all . Rather, it simply avoids the question of why, if domestic 

and workplnce exposures ttre comparable, thc combinmd workplace data do not indicate 

any ETS-lung cancer association . 

The fact that workplace studies pralucc a risk estimate that disagrees with the 

cstimatc derived from aggregated spousal smoking studies cannot be dismissed by 

making speculative assumptions about study design validity . The Icast that should be 

expected is that a diligent cffort be made to evaluate the reasons for the discrcpancy . 

Such an evaluation tnust seriously consider the possibility that it is the spousal smoking 

study dosign that is more scvcrely flawed . As well as many other potcntial confoundcrs, 

the spousal study design introduces sociocconomic status-mediated occupational nsk 

factors. Since there is a tentiency for smokers and their spouses to be oC lower socioeconomic 

status than nonsmoking couples, the spousal smoking stttdy design is likcly 

to confound ETS exposurc with employment in blue•collar jobs that involve more 

toxic exposures . The workpiacc ETS study design avoids problems of spousal concordanec 

with respect to lung cancer risk factors and introduces (ewer potential biases 

and confounders than are present in the spousal study design . Thus, workplace ETSlung 

cancer data are probably less flawed than are the spousal smoking data . 

4. CONCLUS(ONS 

Since probable effects of bias anci confounding have not been adequately accounted 

for in the spousal smoking-lung cancer epidemiologic studics, the EPA's conclusion 

that these studies support a r,tusal infertncc is not jttsti6ed, 

The aggregated workplace data indicate no ETS-lung cancer risk elevation, further 

undermining both a causal inference based on spousal smoking studies and the EPA's 

conclusion that ETS is a Group A carcinogen . The ETS-lung cancer epidemiologic 

data provide no scientific basis for government rzgulation of smoking in the workplace. 

REFERENCES 

BttowNSON, R. C., AI.AVAN)A, M . C. R ., Hetx, L• . T„ AND Loy, T . S, (1992) . Passive smoking and lung 

nncer in nonsmoking women, dnt. J. Publfc Health E2, 1323-t330 . 

DUTLEA, T . L(198E) . The Re/utiwuhlp ojPaslire 5mok/n,t• to Various Ilcaltlh Outcon,rr amonj SeYrnrh 

Day Atlvcntirrt In Cul{'fornla, Ph .D, dissutation, Univenity of Glifornia, Los Ansele1 

FArZV.Nn, W . H. (1993) . Testimony before the U.S. Hotut ojRepuentatlres Subcommittee on Speclalty 

Cropsand Nutural Rerourres . ISBN 0-t6-04169E-1, pD, 99-120 . U .S . Governmcnt Printin=Oftice, Wmhington, 

1?C. ' 

FownttiH. T. H ., CoRRPA, P ., et al. (1991) . Lung cnncsr in nonsmokin6 vromen : A muhitentcr nseoonuol 

ttudy. Canter L•pidemiol . Ilro+narkert Prr .. I, 35-43 . 

Ftantoruy, O . D, Pertrrt, D . R .. AND DAwol. R. D. (1983). Ptsnlcnco and correlatm of passive smokin` . 

Am . J. Public llealth 73, 401-A05 . 

GwttiaNKEL L, AvERtAe)t, 0„ AND JoU®ERT, L . (1985) . lnvoluntary smoking and lung cancer. A asceontrol 

study . Z NurL Concer Inrt . 75, 463-469. 

1At+ttueH, D. T ., TnoM['SON, W. D„ et el. (1990) . Lung cancer and exposurc to tobacco smoke in the 

household . N. ER .L J. Afrd sit R7l-.ctR 

KAar,T, G . C . (1990) . Epidcmiolopo studies of the rd .itionrhip txtwcen pasaive smokins and lung oncer . N 

ln 1990 olnnual Wnter Toxicolory Fonrm, pp . 1E7-201 . Tozicolo6y Forum, Waahin=ton, IUC . Ks,r1 

..T, G . C, ANO Wrxot:u . F. L. (19R4), Lung anccr in notumnkcti Cancer 51, 121L-1221, ~ 

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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 

', I 


-~ ~ 

I


316 LJ :VOIS AND 1 .AYARD 

K1=2s, L M ., KI=U, R . G, AND CIUMNU, J, A . (1992). 1)iucNacia helwyen celf-reponed smoking 

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A study on storuntokint Hong Kong C.hinesc wives with sctoking vcrsus nonsmokissg husMtnds . Soc . Sr.i . 

Ned . 26, 751-'/60 . 

Koo, L C .. 110, AND SAW . D, (19t1) . 1s paasivc smokin8 an added risk fanor for lung cuncer in 

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1.AYAnD, M . W . (1992). Thc backtround adjustttlcnt in risk .uccunent of cnvironmenul tohscao smokc 

and lung ancer . Envfron, lru. ld, 453-461 . 

Lze- P . N . (1992), Environmental Tobacco S'make and Alortallry . KrrBcr AG, Daae1, Switxcrland, 

Lfil:, P . N ., CMASdbEALUN, J ., AND AWEhSON, M . R(1966) . Rclatianship of pusivc smoking to risk of 

lung canccr znd othcr amokint-associsscd diseJses, Br . J. Cancer 54, 97-105 . 

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esposurc to environmcntaI tobaa:o amokc . Cancer Caures C:aural 2, 11-16 . 

PExtZ.STARtI. L• J ., I+IAkIN . G ., MASttN, A. V ., AND 8_:tiowlT7, N . L. (1992) . MiEdatsiGcation of .moktr.g 

status by self-reportcd cigercttc consumption . .1 n . Rrv . Resp . Dlseasr 145, 53-57 . 

SHILATA, A ., PALi~NWI-I{IiJ ., A ., Rosz . R . K., e ; al. (1992) . 1)ictary B-arotgne, cig .arcttc smokint, and 

lung oncer in men. Cancer Causes Conual3, 207-214 . 

StusRtzU, H ., MoRtssin'A, M ., MtzUNO . K ., et al. (1988) . A use control study of lun8 canccr in nonsmokinQ 

womcn . Tahoku J, Exp. afcd. 154, 319-397 . 

SIDNEY, S-, CA..N, B . J ., ANO Mk1kDMAN, G . D . (19n9) . Dicury intake of urotene in nonsmokets with and 

without passivc smoking at homo . .4m, J. F.p,drmiol 129, 1305-1309 . 

SlroCxwr-a .t, H . G„ GowMAN, A . L, el uL (1992). finvironnunt.l tobacco cmoke smd lung canccr in 

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Ret• 51, 33992-34003 . 

U S- Eavironmental I'rotuxiou Atcncy (U .S . E.PA) (1992) . Rcsptratory 1lealrh F,1Rctr ojPassirc SmokinR: 

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WAtltNKNL•CttT, 1 . . E ., Duasck, 0. L, et al. (1992) . Misclusi6cation of smoking sutut in shc CARDIA 

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Wu, A- IL, jiENDrxsoN, H . @., PtxE, M . C-, AnU Yu, M. C. (1985) . Smoking and other risk facwrs for 

lung cancrr in women . J. Natl. Cancer Intt. 74, 747-751 . 

WU-WlWAMS, A . H ., DAt, X . D„ 11tAT, W ., et al. (1990) . Lung cancer among women in north-ast Chinn . 

Dr. J. Canccr 62, 982-9R7 . 

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i 

GENERAL COMMENTS 

The same criticisms that apply_to the spousal smoking risk 

estimates apply to the workplace risk estimates (no actual 

measurements of exposure, failure to account for sources of 

bias and for potential confounding factors, poor study design, 

weak reported associations) . 

As illustrated in Table 1, only two of the reported risk 

estimates 

majority, 

significant . 

are statistically significant . The overwhelming 

16 of 18 risk estimates, are not statistically 

Taken as a whole, these data do not support the 

existence of an association between workplace exposure to ETS 

and lung cancer risk in nonsmokers . 

As recently noted by LeVois and Layardl : 

The EPA' s 

workplaces 

therefore 

cancer, so 

fourth point, that ETS exposure in 

is comparable to home exposure, and 

if home exposure can cause lung 

can workplace exposure, is not an 

argument for dismissing the workplace 

epidemiology at all . Rather, it simply avoids 

the question of why, if domestic and workplace 

exposures are comparable, the combined 

workplace data do not indicate any ETS-lung 

cancer association . 

1 . LeVois, M .E ., and Layard, M .W ., "Inconsistency Between 

Workplace and Spousal Studies of Environmental Tobacco Smoke 

and Lung Cancer," Regulatory Toxicoloay and Pharmacoloay 19 : 

309-316, 1994 . 



LeVois and Layard conclude : 

The fact that workplace studies produce a risk 

estimate that disagrees with the estimate 

derived from aggregated spousal smoking 

studies cannot be dismissed by making 

speculative assumptions about study design 

validity . . . . The workplace ETS study design 

avoids problems of spousal concordance with 

respect to lung cancer risk factors and 

introduces fewer potential biases and 

confounders than are present in the spousal 

study design . Thus, workplace ETS-lung cancer 

data are probably less flawed than are the 

spousal smoking data . [authors' emphasis]

TABLE 1 : ESTIMATES OP pORKPLACE ETS EXPOSURE M LUNG CANCER RISlC IH NY)NS2SOICERS 

STUDY COUNTRY NUMBER OF CASES/CONTROLS GENDER EXPOSURE DEFINITION RISK ESTIMATES 

IN WORKPLACE ANALYSIS 

Brownson, et al ., USA not presented female "highest quartile" of workplace exposure L 2 (0 .9-1 .7) 

1992 

(432/1402 total) exposure in the workplace "no elevated lung cancer risk" 

Butler, 1988 USA 6 cases female worked with smoker for 11+ yr 147 (0 .15-14 .06) 

7 cases male worked with smoker for 11• yr 1 .72 (0_33-9 .04) 

Fontham, et al ., 1994 USA 609/1247 female ever exposed 1 .39 (1 .11-1 .74) • 

Garfinkel, et al ., USA 14/52 female exposure in last 5 years 0 .88 (0 .66-1_18) 

1985 

34/118 exposure in last 25 years 093 (0 .73-1 .18) 

Janerich, et al ., USA not presented both 150 person-years exposure 0 .91 (0 .80-1 .04) 

1990 

(191/191 total) 

Kabat & Wyader, 1984 USA 53/53 female current regular exposure 0 .68 (0 .32-1 .47)' ' 

25/25 male current regular exposure 3 .27 (1 .01-10_6) "• 

Kabat, 1990 USA 44/111 female ever exposed at work 1 .00 (0_49-2 .06) 

37/105 male ever exposed at work 0 .98 (0 .46-2 .10) 

Kalandidi, ett al ., Greece 65/76 (est .) female "between extreme quartiles" of exposure 1 .08 (0,24-4 .87) 

1990 

some v- minimal exposure 1 .70 (0 .69-4 .18)' 

exnosed at work 1 .39 (0 .76-2 .54)' 

Koo, et al ., 1984 Hong 2/4 female exposed at workplace 0 .91 (not given) 

Kong 

Lee, et al ., 1986 Great 15/158 female ever exposed 0 .63 (0 .17-2 .33) " 

Britain 

10/59 male ever exnosed 1 .61 (0 .39-6 .60)" 

Shimizu, et ai_, 1988 Japan not presented female someone at workplace smokes 1_2 (not given) 

(90/163 total) 1 .2 (0 .70-2 .04)' 

1 .2 (0 .69-2 .01)' 

Stockwell, et al ., USA not presented female exposure at work "no statistically significant 

1992 increase in risk" 

(210/301 total) 

10921753 

0 1" BY 1Y,.--; Y{.J6z llZ 


Wu, et al ., 1985 USA not presented female exposed at work 1 .3 (0 .5-3 .3) 

(29/62 total) 

Wu-Williams, et al ., China 415/602 female exposed a[. work 1 .1 (0 .9-1 .6) 

1990 

1 .22 (0 .95-1 .57)' 

10921753 

statistically significant 

1 .1 (0 .86-1 .41)' 

LeVois, M .E ., and Layard, M_W ., "Controversy Over Regulating Indoor Air Qualityc Environmental Tobacco Smoke," comment submitted to U .S . 

Occupational Safety and Health Administration, Docket H-122, No . 3-1067, March 19, 1992 . 

Lee, P .N ., Environmental Tobacco Smoke and Mortality . Basel, Karger, 1992 . 



2

Brownson, R .C ., Alavanja, M .C .R ., Hock, E .T ., and Loy, T .S ., 

"Passive Smoking and Lung Cancer in Nonsmoking Women," American 

Journal of Public Health 82(11) : 1525-1530, 1992 . 

In a study published in 1992, Drownson and colleagues 

reported on results of a case-control study of Missouri women who 

were lifetime nonsmokers or former smokers . This study is notable 

for its large sample size, as over 600 lung cancer cases were 

enrolled, more than 400 of whom were self-reported lifetime 

nonsmokers . The authors wrote : 

In general, there was no elevated lung cancer 

risk associated with passive smoke exposure in 

the workplace (not shown in table) . Only 

lifetime nonsmokers showed a slight increase 

in risk at the highest quartile of workplace 

exposure (OR = 1 .2 ; 95% CI = 0 .9, 1 .7) . 

As the above paragraph indicates, these authors failed to present 

their overall risk estimate for workplace smoking, which was 

apparently not statistically significant . The risk estimate that 

was presented, that is, the one for the most extreme self-reported 

exposure category, was also not statistically significant . 


Objectisrs . The causes of lung 

cancer among nonsmokers are not 

dearly understood . To funher evaluate 

the relation bctwecn passive 

smoke expxosure and lung canxr in 

nonsmok7ng women, w•c conductcd a 

population-based, case-control 

studr . 

Afer,'tods . Casc patients 

(n = 618), idcntined throueh the Missouri 

Cancer Repstry for thc period 

1986 through 1991, included 432lifctime 

nonsmokers and 1So cx-smokers 

who had stopped at least 15 years 

before diaposis or who bad smoked 

for less than 1 pack-year . Control 

subjeeis (n = 1402) were selected 

from dri4'er's license and Medicare 

files . 

Restllu . No increased risk of 

lung cancer was associated with 

childhood passive smoke e .rposure . 

Adulthood analyses showed an increased 

lung cancer risk for lilctime 

noasznokers with exposure of more 

than 40 pack-years from all housebold 

roembers (odds rat)o (ORJ = 13 ; 

95% confidence interval (CI) = 1 .0, 

1-8) or fxom spouses only (OR = 1 .3 ; 

95`'o CI s 1 .0, 1 .7) . When the tuneweighted 

product of pack-ycars and 

average bours ccposcd pcr day was 

considered, a 305'o excess risk was 

shown at the highest quamk of exposure 

among lifetirne nonsmokers . 

Cwtclunoru. Qurs and other recent 

studies suggest a small but consistent 

increased risk of lung caneer 

from passive snnoidng . Compr-ehensivc 

actions to limit smot^:ng in public 

places and worksitcs are weU-advised 

. (Am J Public Health . 

1992 ;82• 1525--1530) 

Passive Smoking and Lung Cancer in 

Nonsmoking Women 

Ross C. E?row7uori, P1tD, Michael C R. Alavanja, DrPlf Edward T. Hoa-, BS, 

and Timo :hv S. Loy', hfD 

Introiurtion 

Although most lung cancer occurs in 

smokers, approximately 9c7c to 13% of 

lungcancer cases in US women develop in 

lifetime nonsmokers .'-S The causes of 

lung cancer in nonsmokers have not been 

wideiv studied, but probably comprise a 

diverx set of factors including eenctics, 

occupational factors, radon exposure, 

diet, and a history of nonrr,alignant lung 

discasc . 

In addition to these risk factors, the 

etioloac role of passive smoke exposure 

has received increastnQ scrutinv over the 

past decade . Numerous studies"0 have 

suggested an elevation in lung cancer risk 

for nonsmoking females who live with a 

smoker, with a summary excess risk of 

appro.tiunatcly 30`-c .=t•= However, several 

recent studiest= -' have shov .n no 

increased lung cancer risk due to spousal 

smoking . 

Limited evidence1-=6 also suggests 

that exposure to passive smoke in cht3dhood 

may inacase risk of lung cancer . For 

example, a recent case-control study from 

New York found that household exposure 

to tobacco smoke during childhood of 25 

or more smoker-years' duration was associated 

with a doubling of lung cancer 

risk .'a 

Most previous studies of passive 

smoking and lung cancer, although suggestrve 

of a positive effect, have had several 

deficiencies . Thesee deficiencies includc 

sample sizes insufficient to singly 

demonstrate significant elevations in risk, 

limited data or, passive smoke exposure in 

both childhood and adulthood, and lack of 

histologic revicw of cases to venfy lung 

cancer diagnosis and to allow analyses by 

cell type . 

To more fuUy evaluate the rclationship 

betwecn lung cancer and passive 

smoke exposure in childhood and adulthood, 

we conducted a IarQe case-control 

study of lung cancer among nonsmoking 

womcn . 

Methods 

Case Group 

Case patients were identified through 

the Missouri Cancer Registry, which is 

maintained by the Missouri Department of 

Health . The Reaistry began collecting 

data on incident cancer cases from public 

and private hospitals in 19-72, and hospital 

reporting was mandated by law in 1984 . 

Registry rcporting procedures havc been 

discussed in more detail elsewhere .= To 

ensure complete reponing of lung cancer 

cases in women for the current study, we 

had Registry staff complete special case 

ascenainment visits to participating hospitals 

. The case series included White 

Missouri women, aged 30 to 84 years, who 

were diagnosed with primary lung cancer 

betwten January 1986 and June 1991 . Selection 

was limited to Whites because of 

small numbers of other racial/ethnic 

Ross C . Brownson is with the Division of 

C}uortic Diseasc Prevenhon and Health Pro 

motion, Missouri Deparanent of Health, Columbia, 

Mo. Michael C . R . ?.lavanja iswith the 

Epidemiology and Biostatistiec Progrant, National 

Cancer lrutitute, Roekvt7le, Md. Edward 

T . Hock is with Information Management Ser . 

vices, Rockvt7le, Md . Ttnwthy S . Loy is with 

the Pathology Deparunent, Universiry of Missouri 

School of Mcdicine, Columbia, Mo . 

Requests for reprints should be sent to 

Ross C. Brownson, PhD, Division of Chronic 

Disease Prevention and Health Promotion, 

Missouri Dcpartrnent of Health, 201 Business 

Loop 70 West, Columbia, MO 6520.3 . 

This paper was submitted to the Joumal 

February 19, 1992, and aecepted with revisions 

August 12, 199? . 

Novembtr 1993, Vol . $2, No. 1I Amcrxan Joumal of Public ltcalth 1525 


groups . The case group included both li.fetime 

nonsmokers and ex-smokers who 

had stopped smoking at least 15 years before 

diagnosis or who had smoked for less 

than l pack-year . From the 3475 cases of 

lung cancer in women reported for the 

study period, 650 eligible patients were 

identified . Physicians denied interview 

perrnission for 24 (4%) of these padents 

and an additional 8 women (1 e/o) refused to 

be intervicwed . The final case group included 

432 (70%) lifetime nonsmokers and 

186 (30rro) ex-smokers . Of the 618 case 

intetvic.vs, 216 were conducted with patients 

thernsclves and 4-02 were conducted 

with surrogates because the patient was 

too IIl to be interviewed or had die .d . Of the 

surrogate interviews, 105 (26°lc) were condueted 

with the patient's spouse and 297 

(74%) were conducted with another rclative 

(c .g„ odspring or sibling) . 

HLirOlCrgIC COrt f17rnG2rZOn of Cases 

Tissue slides were reviewed for histolopc 

verification for 468 (76CC) of the 618 

cases . Slides for these cases were examined 

simultaneously by three pathologists 

(T .L, E .I ., and J .M .) using a multiheaded 

microscopc without knowledge of the refcrring 

pathologist's diagnosis . In surgical 

spedmens, consensus diagnoses were obtained 

v.ith the critcria outlined in the 

World Hcalth Or¢anization classification 

scheme .=9 Rfien orily cytologic material 

was available, consensus was obtained 

with standard cytologic critcria .30 

Connrol Group 

A population-bascd sample of control 

subjects was ascertained by two mcthods 

. For women younger than 65 years, a 

sample of state driver's license files was 

provided by the Missouri Depanment of 

Revenue . For women aged 65 to 84 years, 

conurol subjecu were generated from the 

Health Care Finance Administration's 

rostcrof Medicare recipients .3t On the basis 

of age dismbution of lung cancer eases 

previously reponed to the Registry, the 

final control group was matched by aee 

group to case patients at an approximaLe 

2 .2 to I ratio . All control subjects were 

interviewed direct}y . Of the 1862 potentially 

elig1le control subjects, 335 (18%) 

refused the initial screening interview and 

125 (7%) of those screened and found eligpble 

rcfused the fttll interview . The fuial 

control group numbered 1402 . 

Quesrionnafre Design and 

Adminiriration 

Telephone interviews were con• 

ducted by trained interviewers . The first 

phase of the interview- consisted of a 

screening qucstionnaire to verify the age, 

race, and smoking status of case patients 

and control subjccu . For subjects who 

were screened and found cligiblc and who 

ag7ecd to the full interview, the study 

questionnaire consisted of sections on residential 

history, passive smoke expostire, 

personal health history, family health history, 

reproductivc history, occupational 

exposure, and dietary factors . 

Questions ragarding passive smoking 

focvsed on exposure in both cht7dhood (17 

years and younger) and adulthood (18 

years and older) . For each time period, 

respondents were questioned about the 

sourcee of exposure (e .g ., a parent or 

spouse) . Afrer an indMdual source was 

determined, a series of detailed questions 

were asked on the typc of tobacco used, 

duration of exposure, intensity of exposure, 

and avcraee number of hours per 

day exposed . These questions were partially 

modcled aftcr those dcvcloped by 

Wynder et al .3- In addition to quantitative 

estimates of exposure, respondents were 

asked to cuimate a perceived level of exposure 

during childhood and adulthood 

("During most of your adult years, would 

you say that vour average exposure to 

smoke at home w•as liaht, modcrate, or 

heavy?") . 

Ana lyses 

Odds ratios (ORs) and 95% confidence 

intervals (Cls) were calculated .vith 

multip)c logistic regression .» The lincariry 

of trends in risk according to level of 

passive smoke exposure was evaluated 

with Mantel's one-tat7cd test .s' We initially 

examined numerous potential confounding 

factors . These included age, active 

smoking (for ex-smokers), history of 

previous lung diseases, dietary beta carotene, 

and dictary fat . Of these variables, 

only age, acm e smoking, and previous 

lung disease appeared to confound passive 

smoking findings ; therefore, the results 

presented are adjusted for these factors 

. 

Histologic r,vpe-specific analyses 

were conducted for cases for which consensus 

diagnoses were determined . Thesc 

analyses were undertaken bccause eariier 

studiess•tb-m have shown variations in risk 

by cell type, and biological mcchartisms 

have been proposed that might account 

for these variations .20•u 

Results 

Sociodcmographic and smoking-rclated 

charaeterisda of case panents and 

control subjects have been presented in 

dctail elsewhcre .M In brief, the average 

ages of case patients and control subjects 

were 71 .5 years and 69 .9 years, respcct'rvcly 

. The two groups were also comparable 

on level of education and income . 

Among ex-smokers, the median interval 

since cessation was 24 years, and average 

smoking intensity was 16.4 cigarettes per 

day . 

Tnere was little evidence of incTeased 

lung cancer risk associated w~ith passive 

smoke exposure in childhood (Table 1) . 

This lack of association was apparent for 

both the dichotomous variables (never vs 

evu exposed) and quantitative measures 

such as pack-years . The only suggestion 

of elevated risk was noted for less quantitative 

exposure variablcs (not shown in 

table) . Among lifetime nonsmokers, an increased 

risk of lung cancer was shown for 

those reporting moderate (OR = 1 .7 ; 95% 

CI = 1 .1, 2 .5) and heavy (OR = 2 .4 ; 95% 

C] = 1 .3, 4 .7) exposure to passive srrioke 

in childhood . Risk estimates for most 

childhood exposure variables were 

slightly higher (approximately 20% to 

30%) when analyses included otrly direct 

interviews, although none achieved statistical 

significance . 

An clevate.d isk of lung cancer was 

identifiui for lifetime nonsmokers at the 

lughest quan0e of passive smoke exposure 

in adulthood (Table 2) . At an exposurc 

level of ntore than 40 pack-ycars, Iifetime 

nonsmokcrs showed a 30% increase 

in risk whether the source of exposure was 

all household members or spouses only . 

Similarly, when the product of pack-years 

and average number of hours exposed per 

day was considered, lung cancer risk for 

lifetime nonsmokers was elevated for the 

highest exposure quanile whether the 

source was all household members 

(OR - 1 .3 ; 95% CI = 1 .0, 1 .8) or spouses 

only (OR = 1 .3 ; 95PC CI = 1 .0, 1 .7) . 

Among lifetime nonsmokers, a positive increasing 

trend in risk was noted for packyears 

(P = .06) . Passive smoking-related 

risk estimates for adulthood exposures 

were slightly lower for all subjccts (i .e ., 

both ex-smokers and lifetime nonsmokers) 

than for lifetime nonsmokers alone, 

although the same general elevations in 

risk were notcd . When analyses were limitcd 

to direct intcrvinvs, no clear pattem 

of increase or decrease in risk estimates 

was apparent . Regarding less quantitative 

exposure variables, elevated risk was 

shown for all subjects (OR = 1 .7 ; 95% 

0 = 1 .1, 2 .6) and for lifetime nonsmok- 

15:b American loumal of Public Health November 1992 . Vol . 82, No . 11 


TABLE 1-A.dl" ttd Odds RatSat (OR)` and 95% Confidence lrrtavata (CO fw the Relatlonosure 

during Chtldhood and Lun9 Catxc-r In Wornen, Mlsaourl, 1986 through 1991 

~11 ,,SL~.)jedSb 

LIf2tlrnC NLYSSlTtOk9f7 

Source of E)posure No . Cases No . Ccrmots OR 95% Cl No . Cases No. Corttrds OR 95% Cl 

Al1 hauatlol6 members 

t,}ew 430 928 1 .0 323 802 1 .0 

Ever 185 472 0.8 0 .7, 1 .1 108 364 0,8 0.6, 1 .1 

Ggarette pedc-years 

0 430 926 1 .0 323 802 1 .0 

>0-15 42 129 0.7 0 .5, 1 .0 27 104 0 .7 0.4 .1 .1 

>15-25 31 119 06 0 .4,0 .9 20 91 0 .6 OA,1 .0 

>25 34 117 0.7 0.4, 1 .1 21 87 0 .7 0,4, 12 

Parents onty 

Never 489 1021 1 .0 357 877 1 .0 

Ev¢r 126 379 0,7 0 .5, 0.9 74 289 0 .7 015, 0.9 

Ciyaretie padc-years 

0 489 1021 1 .0 357 877 1 .0 

>0-15 19 90 0.4 0 .3, 0.7 12 70 0 .5 0 .2, 0.8 

> 15-25 27 118 0.5 0 .3, 0.7 17 87 0S 0 .3, 09 

>?5 33 99 0.7 0 .5, 1 .1 21 74 0 .8 0 .5, 1 .4 

°,•dNLzted ror .9e, nmory of pr er.+xis r.rig c3seRSa, and .c:tr-e emo+orq ( ad v.ixecs ort4 

`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, 

ers (OR = 1 .8 ; 95% CI = 1 1, 2 .9) who 

reported heavy exposure to passive 

smoke . 

In general, there was no clevatcd lung 

cancer risk associated with passtvc smoke 

exposure in the workplace (not shoµr in 

table) . Only lifetime nonsmokers showed 

a sllght increase in risk at the highest quartile 

of workpface exposure (OR = 1 .2 ; 

95% CI = 0 .9, 1 .7) . 

Among the 4,58 lung cancers that were 

verified histologjcal}y, the predominant cell 

types were ader>ocaxcinoma (62 .49c), other/ 

mixed cell types (25 .2%), squamous cell carcinoma 

bronchioah-colar carcinoma 

(4 .11,1), and small cell carcinoma (2S5`c) . 

The other/mixed cell type category con- 

sisted mainly of large cell lung cancers, 

though these lacked suff•icient pathologic 

evidence for precise classincation . Table 3 

presents results of cell typc-specific artalyses 

for adulthood exposures . Elevated risk 

was shown for otherhnixed cell typcs at 

more than 40 pack-years of exposurc 

(OR = 1 .6 ; 95% CI = 1 .0, 25). Akhouzh it 

was based on small numbers, a risk estimate 

of 1 .7 was observed for small cell carcinoma 

at the highest level of exposure . 

We also examined risk among 

women who had been exposed to passive 

smoke in both childhood and adulthood, 

in childhood but not in adulthood, and in 

adulthood but not in childhood .7lure was 

no evidence of interaction between exposure 

during the two periods . 

Discussion 

Our study suggests that exposure to 

high levels of environmental tobacco 

smoke in adulthood incTCascs the risk of 

lung cancer in nonsmokers . Exposure of 

more than 40 pack-ycars' duration increased 

the risk of lung cancer among nonsmokers 

by approximately 30% . 'I"ttis relationship 

%vas consistently demonstrated 

among lifetime nonsmokers whether the 

exposure variable was pack-years or the 

time-weighted product of pack-years and 

average number of hours exposed per day . 

Our findings are similar to those of another 

large study of lung cancer in nonsmoking 

womenm that identificd an OR of approxunately 

1 .3 due to exposure to greater than 

40 pack-years of spousal smokingIn earlier studies, the most commonly 

reported index of passive smoking 

exposure has been the presence or abscnceofasmokingspouse 

. Inourdataset, 

no elevated risk was noted for this variable 

. Since our study was limited to 

women, part of the difference between our 

findings and those of earlier studies may 

be due to differences in the effects of passive 

smoke exposure by gender . -Ilx National 

Rcscarch Council's summarv of 13 

studics=t found overall relative risks of 

lung cancer in nonsmokers due to spousal 

smoking of 1 .32 for women and 1 .62 for 

men (although the estimate for men was 

based on few cases) . It is possible that 

men are exposed to other factors (e .g ., 

occupational exposures) that may interact 

w~ith passive smoke exposure to increase 

ruk above that observed in women . Pruencc 

or absence of a smoking spouse is a 

relatively erudc measurc of passive smoke 

exposure, with a potential for wide variabtliry 

in acrual exposure . It was noted in 

one survey, for example, that 47% of 

women married to smokers reported zero 

hours of passive smoke exposure at 

homa.s' It has also been shown that considering 

spousal exposure alone may underestimate 

total household passive 

smoke exposurc .M Another factor that 

may account for the differences in lung 

cancer risk due to spousal smoking between 

our study and earlier studies may be 

time trends in smoking patterns . The de- 

clining prevalence of smoking among 

men39 has probably resulted in decreasing 

years and perhaps levels of exposure to 

passive smoke in the home among nonsmoking 

women whose husbands smoke, 

Contrary to the findings of two earlier 

case-control srudies,'•26 our data showed 

no evidence of excess lung canccr risk due 

to passivc smoke exposure in childhood . 

The risk of lung cancer due to childhood 

passive smoking may have some analogy 

to risk among ex-smokers . After 10 years 

of abstinence, the lung cancer risk for exsmokers 

declines to 3oro to 50% of the risk 

for continuing smokets .p Siuu7arly, lung 

cancer risk due to passive smoke exposure 

in childhood may decline by adulthood, 

espccially in the absence of adult- 

Novemtxr 1992, Vol . 82, No. 11 Amenean loumal of Public Health 1527 


iI ''wt•• *~aw'..rrr .-,~ ;r,r,wt.d nl~YBi~W 3L~ ,d6 

~- - -~_ 

Brv .+nsan ct .I . 

TABLE 2-Adlustrd Odcta RaUoa (Ofi)' and 96% Cortitdcnce Intervals (CR for t1x Relation,chlp txtween Paacatve Srnoke Exposurrc 

duMg Adulthood and LLN Cancer In Wonxn, Mlasourt, 1966 throagh 1991 

A1 SubieCS° LJkti-ne Norrsrnokers 

Souce of Exposvre No . Cases No . Corwnls OR 95% CI No . Cases No. Contro(s OR 95% CI 

AD taus*)O~d members 

Never 221 527 1 .0 170 470 1 .0 

Eyer 394 873 1 .0 0.8, 12 261 896 1 .1 0 .8, 1 .3 

tte -YearS 

0 221 527 1 .0 170 470 1 .0 

>0-15 88 234 0 .9 0,6, 1 .2 56 181 0 .9 0 .6 .1 .2 

> 15-4A 91 261 0 .8 0.6, 1 .0 52 199 0.9 0 .6 .1 .2 

>40 146 264 1 .3 1 .0, 1 .6 107 217 1-3 1 .0, 1 .8 

C'k-ette pack-years x hotrsJday` 

0 221 527 1 .0 170 470 1 .0 

> 0-50 90 261 0 .8 0 .6, 1 .1 63 206 0 .9 0 .6, 1 .2 

>50-175 89 246 0 .8 0 .6, 1 .1 58 189 0 .9 0 .6, 12 

> 175 124 238 1 .2 0 .9, 1 .6 92 192 13 1 .0, 1 .8 

tJ, .wer 287 650 1 .0 213 568 1 .0 

Erer 328 750 0 9 0 .8, 1 .1 218 598 1 .0 0 .8, 12 

Ggatene pack-years 

0 287 650 1 .0 213 588 

>0-15 58 166 0.7 0 .5, 1 .0 32 128 0.7 0.5, 1 .1 

> 15-40 81 258 0 .7 0 .5, 09 54 200 0.7 0 .5, 1,0 

>40 150 266 12 0 9, 15 110 216 1 .3 1 .0, 1 .7 

Cigarelte pack-years x hours/dey` 

0 267 650 1 .0 213 568 1 .0 

>0-50 64 201 0 .7 0 .5,0 .9 4t 161 0.7 0 .5, 1 .0 

>50 175 81 237 0 .7 05, 1 .0 52 183 0.8 0 .5, 1,1 

> 175 126 241 1 .1 09, 1 .5 94 193 1 .3 1 .0, 1 .7 

À4 .s1a7 lor aqe, hmpy of p(ev,a .a lu)g dsewe, ard acttve smo+~Yq (al sut~ec's orYy; . 

°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, 

`The proad of lotai pack yea•s anf everage nurber Of hours ctaosed per cay to pamrve urq-e n the hortA . 

TABLE 3-AtSJusted tOdds Ratloa (Oft)' and 95% Corrfidenae IMerrala (CI) for Ux Re{rrionshlp btrtwesn Pasalve Smoke Exposure 

cturktg Adt>nftood and LuN Cancer In Women, by Hlstolo9lc Type, 6,Ussotxi, 1986 thrwph 1491 

Ade)ocercr~ Other/Maed SquamaJS Ce4 Srnall Cell 

Source of Epostxe No, Cases OR 95 % Ct FJo . Cases OR 95% CI No . Cases OR 95% C1 No . Cases OR 95% Cl 

!+l hot~old members 

Never 100 1 .0 37 1 .0 10 1 .0 3 1 .0 

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 

Cigwete pack-ya- 

0 100 1 .0 37 1 .0 10 1 .0 3 1 .0 

>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 

>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 

>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 

Spoc.6C Only 

Nevet 131 1 .0 48 1 .0 14 1 .0 4 1 .0 

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 

CiQarette pack,/ears 

0 131 1 .0 48 1 .0 14 1 .0 4 1 .0 

>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 

>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 

>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 

'Adxntod ta .qe, hmory at pre~ 1ng doease, arw azfY.v cno+cns, 

hood exposure . In addition, there may be assessment of lung cancer risk due to pas- especially problematic when a large perlow 

reliabt7ity for quantitative measures sive smoke exposure in chiJdhood panic• centaee of surro¢atc inteniews are con- 

(intensity and duration) of passrvc smoke ularly difficult . Reliabiliry and validlty of ducied (as in our study) . Partially because 

exposure in childhcad,•1•'= which makcs measures of childhood exposure may be of these limitations, few studies of child- 


hood passive smoking and lung cancer 

have been conducted, and further research 

in this area is needed . 

Our analyses by histologic type 

showed the largest increase in risk for 

other/mixed cell types and, although the 

estimate was basedon very small numbers, 

for small celU carcinoma . Previous studies 

are inconsistent and often lacking in sample 

size when evaluating risk by cell type . 

Garfin}xl ct a1 .10 found an elevated risk for 

squamotis cell carcinoma and for other/ 

mixed cell typu . Othcrss•ta have observed 

larger elevations for squamous and small 

cell carci.noma than for adenocareinoma . 

In contrast, Wu et al .tt and Fontham ct 

al .m found larger increases for adenocarcinoma. 

An additional difficulry in evaluating 

previous studies of pa,ssive smoking and 

lung eancer by histologic type is that few 

studies have conducted systematic pathology 

reviews to verify ccll type . 

Our study has several major saengths . 

Thc:,c include the large sample size-one of 

the largest serics of nonsmofing lung cancer 

cases to date . In addition, we had relavvely, 

hi.gh response rates fiom bnth case patients 

and control subjects . Finally, we conductcd 

a pathology review of cases . 

The main limitation of our stvdy is 

the possibiLty of recall bias for passive 

smoke exposure variables .'The less quantitative 

measures of passive exposure 

(i .e ., light, moderate, or heavy exposure) 

resulted in larger risk estimates than more 

quantitative estimates such as pack-years . 

Because there is no way to confirm previous 

passive smoke exposure, it is difficult 

to determine the best index for estimating 

exposure . However, we found that 

lung cancer ritk due to adulthood passive 

smoke exposure was elevated at the highest 

quartile of exposure whether we used 

a more quantitative (e .g ., pack-years) or 

less quantitative (e .g ., heavy exposure) 

variablr, . 

Another possible source of bias in our 

study is the large number of surrogate interviews 

for cases . Earlier studies,M-'s 

however, have show-n relatively close 

agreement on most passive smoke exposure 

variables as reported by subjects and 

spouses . We found fairly minor alterations 

in risk estimates when analyses were restricted 

to directly interviewed c.2ses . In 

addition, we compared sociodemographic 

characteristics of direct and surrogate 

case-group interviews and found close 

agreement for most variables . As one 

might expect, the exceptionwas age ; there 

was a tendency toward more younger case 

patients in direct intervicw5 . 

In summary, our study and others 

conducted during the past deeade suggest 

a small but consistent elevation in the risk 

of lung cancer in nonsmokers due to passive 

smoking .'Ihe prolifcration of federal, 

state, and local regulations that restrict 

smoking in public places and work sites" 

is well founded . (] 

Ackno"iedgmeots 

This study wu supponcd in part by Nauonal 

Cancer Instirute eontracts NO1-CF7-1046-01 

and NO1-CP7-1096-Q? . 

The authors gratcfully acknowledge the 

assistance of numerous individuals and organizatioru 

who made this study possiblc . Sandi 

Ezrine, Patsy Henderson, Joan Huber, and 

other staff of Survey Research Associates, Inc, 

for valuable help in all phases of the srudy ; Dr . 

Jian Chang, Carlenc Anderson, Debbie Pinney, 

and Jcanu Shanebarger of the Missouri Cancer 

Rcgistry, NLssoun Dcpartment of Health, for 

assistance in data collection and patient tracking 

; Dr . Ellis Ingmam of the Urtivcrsin• of Mis- 

souri School of Medicine and Dr . Jeffrcy Mcycrs 

of the Atavo Clinic for their assistance in 

review-tng pathology shdes ; Drs . William Blot 

and Jay Lubin of the National Cancer Institutc 

for helpful comments on the manusenpr and 

the tvfissouri Department of Revenue and the 

Health Care Finance Administration for their 

help in selecting populatton-based eontrols 

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19fi6;123 :481-489 . 

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1 S.ul Amencn )ournal of Puh6c Health A :o~-cmbcr 1992 . \'oI 82 . No . 11 


Butler, T .L ., The Relationship of Passive Smoking to Various Health 

Outcomes Among Seventh-Day Adventists in California . Ph .D . Thesis, 

University of California, 1988 . 

Another U .S . study including workplace data is the 1988 

Ph .D . dissertation of Butler . This cohort study followed two 

groups of California Seventh-Day Adventists, members of a religious 

sect who adhere to certain lifestyle choices, e .g ., abstinence from 

smoking, caffeine and red meat . Despite the lifestyle differences 

suggested by membership in this sect, Butler's data have been 

included in discussions of workplace ETS exposure . For males, 

Butler reported a risk estimate of 1 .72 (95a CI 0 .33-9 .04) ; for 

females, the reported risk estimate was :L .47 (95% CI 0 .15-14 .06), 

for having worked with a smoker for eleven or more years . Neither 

was statistically significant . Despite the large number of 

individuals enrolled in the study, very few lung cancer cases were 

obtained . As a result, an extremely small sample size is a major 

flaw in this study . 




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tf1dNEFISTY OF CutFORtdw 

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TM FtMatwnstvp ot Pass,va Smobnq to Vuious 

Haaltn Outcom.s unonq S.wrnh-day Adv.ntists tn Caliiorrua 

A tksi .rtaUon submrtted in parual satUstacUon 

of tt4 r .Qur .m .ms tor ttre daqreu 

Doctor of Publr. Healtli 

by 

T*nsnc . LssLa SWw 

1988


TM dusarution ot Ttrr .nc . LtsJ,. Buti.r a approv.d. 

Sandv Grs.niuui 

Wilum SfwruCk 

Unricrsrty of CaJdortua, Los Angales 

1988 

Bubua V=nsr, Commatee Char


A 

~ -1.._ 

.` 

© CopynVM by 

Terrencs L*slr BuU.r 

1988


Dadicat .d to the mwmory pf my moth .r 

Sarah Joan Burd .r11922•1987) 

A IHs of Immsa"abis qualnies 

ri


Ust of Fquret 

list of Tahies 

TABLE OF CONTENTS 

Acknowi.dqements zw 

Vrta. Pubticanons and Prnsentanons za 

Absua a xx 

Ctupter I INTRODUCTION 1 

1 .1 Sadcground 1 

Paqe 

12 Researcti Hypott"as 3 

1 .3 SpecifiC Ob}rzctnws 4 

1 .4 Defrunons and Classtinnon nf T.rms 5 

1 .5 Sl9ruficance, Relevance and R.thonale 8 

1 .6 Orqancsnon of Thesa 9 

Chapter 2 UTERATURE REVIEW 11 

2.1 Introducnon 11 

2 .2 Companson of Mansiream and S+dsstream Smoke 13 

2 .3 Measurement of Passnre Sm>kan9 Ezpouxe 15 

2 .4 General HeaJth Ett®Cts 20 

2 .5 PtausibiYty of a Heatth Effect 22 

2 .6 Lung Cancer 23 

vw


PaQe 

2 .7 Ott>.r Cancers 32 

2 .8 ti .art Dtsaase 36 

2.9 AJI Caus. Moriahty 40 

2.10 Summary 40 

Chapter 3 METHOOS 43 

3 .1 Bactcpround of Study 43 

3 .2 Study Destgn 52 

3.3 Dsscriptwn of tM Study Poputatwns 52 

3 .4 Data Dscnpuon 58 

3 .5 Outcortw Ascenanmant Procedures 61 

3 .6 Pass+ve SmoWn9 Exposura Assassment 65 

3 .7 Delntttons of Other Exposure Vanables 70 

3 .8 Data Anays+s and StatuticaJ Mslhods 76 

3 .9 Lirtrtahons and Potenuat Problems of Study 79 

Chapter 4 DESCRIPTIVE STATtSTfCS 81 

4 .1 Spouse Pars Demograpruc Data et 

4 .2 Smoknq Exposure 82 

4 .3 AHSMOG Cohoh Demographtc Data 90 

V


Pa9e 

Ctupte . 5 LUNG CANCER RESULTS 97 

5 .1 Spouse Pars Cohort 97 

5 .2 AHSMOG Cohort 105 

5 .3 Summary 112 

Chapter 6 SMOFaNG RELATED CANCER RESULTS 114 

6 .1 Spous . Pars Cohort 114 

6 .2 AHSMOG Cohort 131 


Chapter 7 ALL INCIDENT CANCER RESULTS 140 

7 .1 Spouse Pa'rs Cohort Inddent Cancars 140 

7 .2 AHSMOG Cohort AJI Incident Cancars 145 


Chapler 8 MORTAUTY RESULTS 153 

8 .1 Spouse Pars Cohort - Ali Cause MonOty Resufts 153 

8 .2 

Spouse Pairs Coh«1- Iscrserris Herrt Disease 

Mortality Resutis 160 

8 .3 AHSMOG Cohort - A8 Cause MortaJity Resutts 163 

8 .4 

AHSMOG Cohort - Ischemie Haart Disease 

Mortality Resuns 

173


Paqc 

e•5 SumerwY 176 

Chapt«' 9 DISCUSSlON AND CONCLUSIONS 180 

9 .1 Data Ouatity 18D 

92 Lung CancK t67 

9 .3 Smo+cmq R.lat.d Cancsn 191 

9.4 Csrwcal Canctr 194 

9 .5 All ~Cid.clt GuK1ri 196 

9 .6 Mortaltty Rautts 198 

9 .7 Condusans 199 

Rt/er .ncss 203 

Appan6oes 1 Gbssary of T4rmmotoqy and Abbr.matlorts 214 

2 AHS C.nsus Qu.stiomair. (1974) 216 

3 AHS lits" Qwstionrsalr . (1976) 226 

4 A1dSMOG Qwstionnair* (1977) 246 

5 AHSMOG Qu*svonnainl (1987) 254 

6 Drtta Cdleehon Fom1s 269 

1977 Nospitaf Hisiory Form . 270 

1883 Hoso+tal Hkstory Form 271 

bischarga Diaqrwsia Forrn 273 

Tumor Abstraet Form 275 

NI


t15't OF AGUaES 

Fiynr• 3 .1 Row Criar1 of Advennst HMttti ShKly 47 

TabN 1 .1 

Paqa 

32 Firtabonstwp of Spous. Pars arxf AHSMOG Suo- 

Populatiorts to the AOvantist Health StuOy 

Incid.nc. Poputatwn ' 53 

tJST OF TABZF.S 

Smoiclnfl Fi .tatsd Canoars 7 

2 .1 D+stribunon of Consutu.nts in Manstraarn Smok• 

(MS) and >n. Rabo of Sioestnam Smoke (SS) to 

MS o/ non-fih.r ciqa»ttas 14 

2.2 Summary of Cas. Controi Studi.s of Lung Canc .r 25 

2 .3 Summary 0 Cohort StuCiss of Lung Cancor 31 

2 .4 Summary of Studas of Other Cancera 33 

2.5 Summary of Studi.s of H.an Dmeasa 37 

2.6 Summary of Studss of AJ Causa Mortality 41 

3.1 Aq .-Standarditrd Mortaiity fiatios @or SNretad 

Causes of Death Among 25 .000 Wfuto Calitoma 

AdvenCSts. 1 960-19L0 45 

3 .2 

8asa LUna Vutablss Msasut .d on ttw Thrs Sa1t- 

Admntst .md Owsbonnarea . 1974•1977 50 

3 .3 Spous . Pars Cohort : S .N .ct.d D.salptrv. Dan 55 

3 .4 AHSMOG Cohat: Ssl.et.d D.acriptn+. Data 57 

3 .5 Spous. Pairs Cohort : Spouse Smokrtg StatuY n 

Marnaqe 68 

vii

I 


Tab1• 3 .6 

Paqe 

P .rcentaQ. Agresm.rit Batw..n two MtthoCs o1 

Class~ Husband's Smoknq Sunu in Marrap• 70 

4 .1 Spousa Pairs Cohort: Sax-SPscifiC Nsbibution of 

Aqe al LO by Ape Groups 01 

42 Spouse Pairs Cohort : Sex•Specific D+suibution ot 

Smokvp Siuus. 1976 82 

4 .3 SFOuxa Pairs Coftn : Sax•Sp.dflc ®+stn4uaon of 

MumCNr oi CiguMtts p49utvfy Smok" 83 

4 .4 Spov" Patrs Cohort: Sax-SptCtfiG Dismbubon of 

Nurnber of Yaars Fi .qutvty Srrwk.d 84 

4 .5 Spouse Pairs Cotsort Sax•Sptd6c Distritxnion of 

Pack Years o/ Cisar.ns Smoked 85 

4 .6 Spouse Pairs Cohort Smakxiq Status of Spouse 

Pairs 86 

4 .7 Spous• Pairs Cohort: Spouse Smokin9 Status in 

Marnaya 

4 .8 Spouse Pars Cohort : Ssx-SPscific Mortality, 

1976-1962 . by Unde(" Gausas a8 

4 .9 Spouse Pairs CoAon: Ses and S+t! SpaotliC 

InaderM Ca"s of Cane.r, 1977•1fl82 89 

4 .10 AhlSt./QG Cottiort: Srx-Spaeifio Distnbuaon of 

Age CwOups 

4 .11 AHSMOG Cohort Sax-Spstafic Datribuiion of 

&moiunq Status 

4 .12 AHSMOG Cohm Ssx•Spscific Octtnbuuon of 

Cigar .n .s Smoked 

4 .13 AHSMOG Cohort: Sex•Spacific Distribution of 

Ysars Smoked 92 

ix 

87 

90 

91 

91


Paqe 

7aWe 4 .14 AHSMOG Conort : Sex•Sp+ahc DWjbubon ot 

Pack Years o4 Gparenes Srtwkod 92 

4 .15 AHSlAQG CctWrt : Sax-Splahc Daubutbn at 

Yean Lrved vrsth a Smokar 93 

4,16 AHSMOG Cohort 5ax-Sp .cftic prstribut,on ol 

Yeant Wark" wrCt a Smokrr 94 

4 .17 AHSMOG Cohort Sex~S~ec4fic Mortalrty . 1976- 

1982. by und.rty+nq Catq.s 95 

4 .18 A!-tSMOG Cohort Sax and Sjte Speclfic incttlsnt 

Gasrs ot Cancer . 1977-1982 »G 

5 .1 Spouse Pars Ftmatea : Histohgy d Lung Cancer 

Cases 98 

5.2 Spoaue Pairs Females : Ltnp Gancer, 1977-1982 . 

D+stnbution of ktadent Cases . Person Y.us, and 

Inc+dencA Rates by Age Grntp uKi Husbands 

Smokny Status n 1Aarnape 99 

5.3 

5 .4 

5 .5 

SPotus Pars F*rrtales : Age Adrusted Rate Ftat,os 

ol Lung Cancer . 1577-1>3E2, for Sekrcted Faeposiue 

Factcxs 

Spouse Pa+n Femaie Non-Smokers : Aqe Adfustad 

Rate Ratio Iw Linp Gancer, 1977-19M tor 

S.1s1.d Exposure Faators 1pA 

Spouse Ps+rs Fomate Non-Smokers : Cornpanson d 

Lung Cancer. Aqe AdEusisd Rat. Flatros IGr 

Exposure to Stwusa Srr+o~ usrnq Dinerent 

SI2USUCa1 mettWr*s 

5 .6 AHSMOG Cphort : HlstoloQy d Lunq Cancer C.zsss 106 

5 .7 AHSMOG Gurrent Non-Smokars : Lung Cancer, 

197'1-1982, DSstrrbuuon d Inpdent Cases, Person 

Years and Incdence Rates by Age Group ane 

Yeus l.rvW w+tn a Smoker 107 

a 

101 

105


Tab1e 5 .!! AHSMOG C+xr`nt Non-Smokers : Lrxtq Cancer, Page 

1977-1982 . Ckstrbwon of ltvNdent Ca.ses . Person 

Years and tncrdence Rates by Age Group and 

Years Worked wrth a Smc+ker 108 

5 .9 ALHSMCY Fernales : Adjutted Rate Rntbos of Lung 

Cancer . 1977-19i32M for SMected Exposure Factors, 110 

5.10 AHSMOG Males : Ad}ust.d Rate Rat,oa of Lung 

Cancer, 1977-1982. For S.lected ExPosure Factors 11 t 

5 .11 AHSMOG Lung Cancer Adjusted Fiat . Rat,os for 

Varying Years and Types of PaSsive Smoking 

E, tsasur• 113 

6.1 Spouse Pars Females : Site Specific Distrtbtmon 

of Smoking Related Cancers 115 

62 Spouse Pairs Ferrules : Nt Smoking Related 

Ca .ncers, 1'd77-1982 . Distnbumon of irtoldent Cases, 

Person Years and Incidence Cases by Aqe Group 

and Husband's Smoking Status in Mamage 116 

6.3 Spouse Pars Females : Age Adjusted Rate Ratio 

of Srralang Retided Cancer Exdt6ng Lung Cancer 

tor Selectod Exposure Factors, 1977-19t32 117 

6 .4 Spouse Pairs F.rtules : Age A4{u:sted Rato Ratio 

of All Smoking R.tst .d Cancer lot SefeCted 

Expoux . Facior= 119 

6 .5 

6.b 

6 .7 

Spouse Pars Female NonSmokafs : Age Adjusted 

Rate Ratio of Smoking Related Csneer Exclfidmg 

Lung for Satected Exposure Facioes. 1977-1982 121 

Spouse Pars Female NonSmok .rs : Age Adjusted 

Rate Ratio 01 Smoking Related Cancer IndudNng 

Lung, 1977-1982 . for SNect.d Exposure Factors 122 

Spouse Pairs Frmale Non-Srtsokars: Smoking 

Related Cancers Ag. Adtusted Rate Ratios for 

Females Married to a Smoke{ or Mamed to a 

Non-Smoker 23 

n


P aqe 

Tabte 6 .6 Spouse Palrs Females : twnrical Cancer, 1977- 

1982 . Diwibut,on of Irxad .rtt Cutas, Peruxt Years 

and Inadence P„^.tas Ly !qw Group artd Husband 

Smor


Page 

TaGe 6.18 AHSMOG : Ai Srtwkinq R 

.tatad Cartcers Age Atttusted Rate Ratio for Vary»p Years and Types 

of Pass+ve Smokx+q Exposura 138 

7 .1 Spouse Pars Ferriales : Ap Incident Canwrs, 1977• 

1952, Drstrbuuon ot anoWnt .r.ases . Pe.ison Yeara 

and Inadence Ftates by Age Group and Husband 

Smokrnfl Status n Mamaqe ' 141 

7 .2 Spouse Pairs Fsmsles : Aqe Adjusted Ftate Ratio 

oi All inadertt Cancsr br SektieC Exposure 

Factors.1977-1982 143 

7 .3 Spouse Pars Non-Smokusq Females : Aqe Adiustsd 

Ftate Ratio of A!i hcidux Cancar, 1977-19E2, for 

Sebect.ci Exposure Factors 144 

7 .4 Spo+1se Pars Females : Adjusted Rate Fttmo ot All 

tncident Cancers, 1977-1982, for Selected 

Exposure Factors 146 

7.5 AHSMOG Current Non-Smokers : All Incedent 

Cancers, 1977-1982 . (hstnbubon of bncWent Cases, 

Person Years and Incidence Rates by Age Group 

and Years Lived wrth a Smokwr 147 

7.6 AHSMOG Curreni Non-Smokers : All h„rclent 

Cancers, 1977-1982 . pisiribuUon of dncdwu Cases . 

Person Years and Mxtidence Rates by Age Group 

and Years Worked w+th a Smoker 148 

7,7 AHSMOG Females : Adjusted Rate Ratio of AII 

Incident Cancers, 1977-1982, for Selected 


7.8 AHSMtJG Males : Adjusted Rate Ratio of All 

Incident Cancers, 1977-1982, Ior Selected 


8 .1 Spouse Pars Females : A11 Cause Mortainy, 

1977-1982, OLstnbut)on of peaths, Person Years 

and Inadenca Fiates by Aqe Group and Husband 

Smoknq Status n Mamaqe 154 

XIN


Page 

Table 82 Spouse Pus Females : Age Adjutti.d F;a1a Ratio 

of AI Natural Cause AAortality, 1 fi76-1982, for 

Sel.cted Exposure Factors 156 

8 .3 Spouse Pars Non-Srralanfl Femalts : Age Adiusted 

Rate Ftat» of Ab Natural Caus . Alortaib, 1976- 

1982, br Selected Exposure Factors 158 

8 .4 Spouse Pa,rs Females : IsdMrrrc Hrart Ditease 

Mortality, 1976-1982, !)istribubon of Dsaths . 

Person Years and krcidenca f3ates by Age Group 

and Husband Smoknq Siatua in t4larnafle 

8_S Spouse Pan Non-Smokinq Fsmales : Age Adjusled 

Rate Rata of lsch.rnc Heart Dtsease t,Aortaity. 

1976-1982, for Selected Espmxe Factors 162 

8 .6 AHSMOG Curr .nt Non-Smotcers : All Cause 

Mortality . 1976-1982 . Distributicn ot Deaths . 

Person Y .ars and Incid .nca Rates by Age Group 

and Yaats llved wRtt a Srnacrr 16a 

6 .7 

AHSMOG Currant Non-Smokefs : All Cause 

Mortality, 1976-1982 . Dutributwrt of Deaths, 

Person Years and Incidenc• Rates by Age Group 

and Years Worked with a Smoker 

8 .8 AHSMOG FemaJes: Ag . A6)ust.d RaU Ratio of 

All Caus. t,Aortality, 1976-1982, /or Sebct.d 

E :poura Factors 

8 .9 AHSMOG Males : Age AdjuSfed Rate Ratio of All 

Cause Mortality, 1976-1982, for Selected 


8 .10 AHSMOG Curr.nt Non-Smokars: tsChsrmc Heart 

Disease Mortahty, 1976-1982 . Distribution of 

Deaths. Person Years and Incadsno. Ratss by Age 

Group and Yeats Lived with a Smokef 

nv 

161 

165 

167 

171


Paqe 

TaW.8 .11 AHSMOG taxrsm Non-Smok.rs : 6sctsarnic Heart 

Drsaast Morta4ty, 1976-19Q2, Distributwn of 

Dautu, Persort Years and incid .n>~. Rat®s by f.q. 

Group and Yraars Worked wrth a Smoker 172 

e .12 AHSM4G Females : Aqe Arijusted Rate Ratio of 

Isch .rric Haart Assaafe L$orsaliry, 1976-19lt2, tor ~ 

SN.aad Exposure Fscoors 

e .13 AHSMOG Maltt : AQe AcffWRtd Rate Rauo of 

isctt.rrrc H .art Disaas. ftAarta[tty . 1976-1982, f r 

Se1ect.d Exposurs Factcrs 

9 .1 Spouse Pa/rs: Subjw Smokinq Status Perc .rtt 

Apr.am.nc Between 1978 artd 1967 Responses 182 

92 Spouse Pairs Females : Percent Aqr*.mant 

Batw*.n Cr.at .d Varnbl. 'Husband Smoked fn 

Marnaq.' and 1987 F4esaor4sa 'Lmd wRh Husband 

who SR1oked' 184 

9 .3 AHSMOG Cohort: Aqrsrt> .r1t Between 1977 and 

1987 Responses to ETS Expown Oueruons 166 

9 .4 A Compuison of R .4atiw Risks of Lung Cancer 

for ETS Ezposwe among tM AHSMOG anC Spouse 

Pars Cohorts 

9 .5 A Comparison of Retuiw Risks of A : Smokinq 

Fietat .d Cano .c toc ETS Esposur• among tt-* 

AHSMOG and Spouse Pars Cohorts i93 

9.6 

A Cornparison of R .latiw Risks oi All lncrder» 

Canc .fs fox ETS E:posure amonq the AHSMOG 

and Spouse Pars Cohor¢s 

9 .7 A Comparison of RNatiw Risks of As Cause 

Mortality lor ETS Expoetre amorty tt w AHSMOG 

and Spouse Pars Cohorts 

174 

177 

1a8 

197 

9 .8 A Comparison of Relative Risks of tschemrc HOsrt 

Drsaase for ETS Exp~osixe among tM AHSMOG 

and Spossa Pars Cohorts 202 

xv 

201


CH/1FTHR 5: LUNG CANCER RESULTS 

In Uus chapter the results of ttk km9 cancer analyses are presented tor 

both the spouse pairs females and tM AHS/.1OG cohon. For the spouse 

pars femabs the hwtial analysas rtclude both the current and past 

smokers . Hovrever, later analyses are resuided to ;4 non-smolunfl 

poputation of th+s cohort. Akhouqh 0,4 major variables of interest afe 

the passrve smo" ezposures, other sefected factors are chosen for 

lndusan n the anatyses because triey may be irxlependent nsk factors 

or have some protective ettect on the outcome . TThe methods of 

analyses induded the calcuiation of a anude measure of ettect and 

stratdied anatyses . 

5.1 SPOUSE PAIRS COHORT 

In the ferrale population of tfle spouse pairs cohort nne incident Cases 

of pnmary king cancer were diagnosed duenp the toiow-up period 1977 

to 1982 . Histoto¢cal confirmation was obtarted for eactt case and the 

inforrnation abstracted from medical pamoloQy reports . The distnbuuon 

by histological type ts presented 'n Table 5 .1 . S+nce there were very 

few cases these were grouped together for analyncal purposes and no 

eNor1 was made to drfterenuate by vanous tustoloqicat types . 

97


14Mobqcd TqVO 

t arp. cH urcx+o+rr 

ox ar qrv,arna 

TALILE LI 

Si'OUSE PARS • FEMALES 

iA3TOLD0Y OF 11LK1 (CMJ .'FA GAM 

Ap.roqrcmpm4 7 

A1I ths cases occurred in the age ranys of 45 to 69 and ony one of the 

rans cases was diagnosed n a former srnolcer . No cases occurred among 

females ctass,hsd as current smokers whiis eigM ca .ses were among nor- 

smokers . Table 5 .2 prtsants ths disatumon of inadent cases, person 

years and inadence rates by tsn ysar age Qroups sccordinq to ttw 

smoknq status o1 subject and spouse . 

A stratdied anaysrs, stratdynq on ten year aye groups . was pertormed 

and Mantet-HaenszN turnmary rate ratiGs and corresponc~ng 95! . 

conlidence ntervals were caka,fated 1or seiected exposure tactors . The 

inadence rates, crude rate rauos, age ad)usted rate rauos, confidence 

intervals and p-values are stwwn in Tabe 5 .3 . The ditterences between 

the crude rate ratios and adjusted rate ratios indcate that there was a 

98

c 

i.rVV !'S Ei'G(.ro(s 


u 

d 

T ABt E 5.2 SPOUSE PArtS - tENtAt ES 

LUNG CANCER (1177•M02) 

Dt3TRJBU110N OF RiC/OEHT CASES. PERSON YEARS A1q MCIOEMCE 1'1/ITES NY AOE GROUP 

ANO Hl1S8AWD SMOKING STATUS 1N &tARfNA(DE 

A0 . ci-up 

MWKE _~~QtL''a110KEtt 

1K£ Si4OKF$__ 

FRfSBAND SMOKER HUô8AN0 NbPt SMOiKER IRt3fIM0? SMOKER II1tSBNW NOff SMOKER 

C.asss! RaW Cas.d RsN/ Cs.>tl ReW CassJ R»d 

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 

26-3R 0 9.2 000 0 800. 0 00 0 711 0.00 0 Mm 0.00 

3.5- .A 0 1652 0 00 0 1%37 0 00 0 t99 000 0•ti 000 

16-64 1 2190 4 .67 2 l520 2.10 01011 000 0 042 000 

6544 1 3000 3 .33 2 ®570 2.33 11240 9 .09 0 976 0 00 

65-71 1 2169 < .113 1 6900 1 .67 o' 02! 0 00 0 305 0 00 

75-01 0 602 0 00 0 2112 0 .00 0 70 025 0 39 0 00 

as 94 0 63 0.00 0 220 0 00 0 0 0 .00 0 L 000 

toul 3105)0 2/H 613052 1 .1s 1 46" 2.14 03610 0 00


contounding eftect by aqe tt7at to some extent was accounted ta n the 

stratdied analysis . The smal rxxnber ot cases and tow statabcal power, 

militate against the pouibiiity of achi .vuN stansticalty srgndicarn 

resuits . Pt is also mposs#Ne to sssass eftect mod'dication witt, so tew 

cases . 

For our ma(ar exposure tactor of irsterettt husband smokng status n 

marriage, summary rate raWs of 1 .94 (95% C .l. 0.46-824) and 2 .47 (B5• . 

C .I . 0 .29-21 .te) were obtanad for past and currenn exposure respectn+ely 

when compared to the refererd group o1 navef exposed . A smilar 

doubbng of the nsk was observed wnen the husband's smoking status 

was dichotomued nto never and ewr smoked, RR of 2.04 (95% C .I . 0 .5d- 

7 .55), No increased nsk of king ctnqr was observed in this popu(ation 

for the subiects own smokng sYariis . Fiowever, when smokers of more 

than ten pack yeus oi caga»tte amok»g were tanpared to the referertt 

group 04 non-smokers iTere was increased risk obserued, RR of 2 .22 (95% 

C .I . 028-17 .74) . The sofitary case n ttN ecposed category ikustrates 

the equivocal nature Ot these resutlf . 

There is a suggestion of a decreased risk for those subtects who have 

anended college versus ttwse with a high school educaUon or less and 

an increased risk tor subtects with blue colar work,ng spouses compared 

100

0 

TAIILE 5.3 SPOUSE PAdAS • FENWII E5 

AGE ADJlJ3iED RATE RASIQS Vltl) OF 111F43 CJVICER 41177-11t2) 

fOR 3ELECIEO EJO*OSUIIE FACTORS 

f.ct« L .,.ds ' Cs.'J • Vad (', .ud. Ad}est.d 

Pr.on Y.r. 10 i'V N(1 /1R- 06% C.1 .) 

1 hesbrd SmoM.+O F/ .v.r 6 A7270 106 ft .l. Rd 

s1aR» n Prsi J 11564 259 2 44 1 .94 (0 46-92J1 

mareu{7• Curnrd 1 3912 256 2.41 2.47 10 2931 _ 1 ./ p -0 69 

l lusband smok.d No 6 4727. 106 Rd. Rd . 

It, r„~„vq. Vs 4 15560 257 2.4J 2 0o t0 .61-7 .651 P' 0 27 

F .mat" rrio4irq Nw.r 0 54091 146 Rs/. Rsl. 

stalut P.sl 1 755! 132 091 0/18 10.11,{92/ p•0/l4 

Curnni 0 8e4 0 0.00 0 00 

F:meh 9.eo4od Non-sa+mU.r •54i91 146 RN. Rsl. 

Smowr 1 8443 lii 001 0.i0 (0.10-1 .3i1 p∎0.03 

Pack y..rs d Noa+. 156772 14/ Rd. ArtU 

t.nokin0 Mnuf. 0-10 0 3534 0 0 00 0 00 

> 10 1 2e27 354 2 51 2 22 (020-17.741 p .0 5S 

EducaNM lkqh 9cAod 421036 100 Rd. f;s[. 

CoMOqr • 4 4J26] 116 061 0 75 (0.20-2 1131 p- 0 64 

Liw in nr.i v.s 330201 99 Fl.l. R./ 

~'~j ~iy roa No 632490 154 1 55 1 .59 (0 J6 6 65/ p• 0 SJ 

~-ii~ Y~_,-.lV~~r~'ylll.r 


a

d 

9V YTSr 0S ryv 0z 


T/IEILE 5.3 cawnm.d 

f actor Lr.l. ' Cassd 

P.roa, v.w tO P1r 

Cends 

Ra 

A4rsW 

r1R- hs% C.l) 

Syous. Wha. Caaar 234665 66 R.1 R.1_ 

Oocup- Beu. Cosar 626120 230 3.96 4.16 t0 .78-22 .161 P' 0 10 

feuA kds. 11 - tras w.a 126169 153 R.f_ Nl . 

•-10 lrnst w"k 423951 167 1 .0! 1 .22 10 31-4 101 

0-3 Mm.s w.w 1 12005 N 0.6f O.N IM0)-6 .011 p1 0 67 

R.u-Cardwr NqA 422104 171 Rs/ . Rs1. 

bn0. 9406wm .19a.2 201 1 .12 1 .23 (0.31- . .1/21 

0 lo,. 1,21317 47 0.26 0.31 p.03-2 .92/ P"0 .46 

' pesa.prncol M casss snd pnson yws Ms dw b 

mrarq v.lust n s.pos.rs Isdat ToUf 'ub,.eb - 11 .060 

• RsN p.« I nrwon pwson rws lunp Canc.r Csss -9 

~ µamN Ns.nst.l summ.ry uN nNO PRR/ - s6p+st+d ia "0 7otd 0'caam tloce - H.407 

Rd. R.1«aA prOnp


to subt.cti with wtwt, cotlar woricir>q apousas . Mowever, bcth rasutts 

ara subfect to biss because d thw unwwwn csassificat,on of one of tt,e 

cases and ttts rttissrV nurnber d p .rson years . 

Since tttere was only otte case among tf» 1 .475 ftma}.s who had ever 

smoked, k was d#fiauti to assass the lntk*nc* of active smoldng on t1x 

overall .#tact of ETS sgxosurra. Th .refon hxtt>.r stratified artiatyses 

w.re restncted to ttK 9 .370 never anokinq Iemalss . The results oa 

these analys.s ar. presant .d n Table 5 .4 . Somewhat similar resutts are 

otuerved as n ihe prwbus analysis and t'he same caveats conceminq 

ettect rnodihcauon, bias and sutistrcat sipniflcance aApiy. For the 

vanable husband smoked in rnaniaqe, the aqe-adNsted rate ratio was 

2 .02 (95'i. C .I. p .48-8 .56) . 

An additanal analysis usnq tfK conditional maximum EkeGhood mmator 

and an exact method tor spars~ data was pertormed and the nasid! a 

compared with the Mantel-Maeruzei estimates in Table 5 .5 . Tnese re"s 

have sirrulat pont lstmatas with tM mid probab+ttty exaCt bnornal 

confidence intervals beinp somewhat w+du and more conservative . 

103

NVV L .-7 ® . .'T C.i llZ 


TAdLE 5 .4 

SPOl7SE PPi1S - FEM1L .E WON-S/iOaEAS 

A[1E AD.R7STED RA)E R/17109 (f" FOR U1N0 CJIF7CER ftf77•1M2y 

FOR SELECIED E7fPOSURE FACiOFt9 

Factar L.../a ' C1's. ./ 

P.rson Y.us 

• 1}aw 

~ PY 

Crwd. 

RR 

Ae~shd 

RR- "b76 C.LI 

IbsWrd$mofaYtO N~oN 6430?7 11t Rof. Rd. 

status o P .st 2 i090 247 2 13 1 s! 10.32-t.pl 

n.una" CwI .nl 1 2466 102 341 337 t0 .3f/-21.051 p-Q M 

Misb .nd « No 6 43007 I ti RM. 71d. 

b wurr..p . Y.s 310576 2!4 2.45 202 10 N-6 661 p-0.32 

Edustics IfipN 3cMd 316063 te7 Rd. FM/ . 

g CoMO. • 631670 129 069 0.06 p0.20-3 971 p• 0.02 

Lkv fn nsrai Ys 3 26013 115 R.i . Rd . 

o.. No 427694 144 1 .26 1 .30 (0 .21-6 H 1 p . 0.73 

9ponta WtrN tollar 231217 E4 FFaI . RAI1 . 

pccup- BOw co4r 420768 269 4 .61 4.19 10 f0-2t.71) p .0 06 

g®b Carelur F40A 410454 206 PAL RN . 

Y1dos RMOcun 311065 176 0 65 093 (0.21-4 .17) 

Low 117660 67 027 033 (004•211% p-05! 

Dsci .pwKrs n c .s.s and pKton y.rs re Guw to 

~•a+q .rua n•.posw• Lctoes Tdal S„bpcts - f .370 

/1n* pw I nwwn pwsm y.ais LunO Gi+cw Casos -• 

Mam .i iu.nuN summary caas roo 1OR1 • .dlusNd ta ag. To1al P.rsa+ Y.ars - 54 $98 

Rd tht.r.M piwp


TAN .E a .f 

Si'OtlSE rAitS - FfA4ALE MOii-S00WRS 

A COtiPARI*aL1N OF Llt*lp GMCEfi AliE ADA1STM iNTE MTIOS 

FOP D0'OSUFlE TO 3pOIJSE aM010rKi lR3t+lli 

OFF9*NT $TATISTICJI . METt'100S 

FACTOR tFYELS • sETFK10 

LC,JUSTED 

M 05'Y. C.L) 

F4,abard fmdied No i'4=7 MMU6144"nusi RM . 

n Marnaq. r .. 11051s 2.02 ro .•a.a.lAi 

rb µanTom, t .&Gi+,ooe a.r . 

Ys 201 )0.9l-L7s1' 

• taaa DKSOn yrars 

ôd MObWh Ir,A .ev»n/ enomrl CW1FK%nrc+ MW rv.i• 

5.2 AF-tSiA 0G C'.O FiORT 

purr>9 the yeus 1977-1982 tttuteen incidertt casaa o/ kng cancer w.re 

diaqnosed in th4 ourrarn non-smoke«s a the Ai-tSMOG cohort Seven or 

the cases were maMs and six w .re Lmsla . ThA hictobqicsl types ot 

tumors are presented in Tabl . 5.6. As witft tne spouse pairs cohort the 

most predortrnant histoloQieal type was adonocareinama. However, all 

Ptisto)oqical types wera grouped to9etfxK tor anYyUCnI purposas . 

105


TABLE 5.6 

NMSMOG 

HlSTOLOGY OF LUNG CANCER CASES 

Mestoioqicai Type Idai. F.male 

Large al carcinoma 1 

Circnortsa NOS 1 1 

&quamous ca1 carcinoma t 

Adenocarcinoma 4 4 

Unknown 1 

For females, cases occurred in the age range of 55 to 94 years while for 

maes, cases were fimqed to t?» 55-84 yaar aqe range . The disvifwtton 

of ncident cases, person yeafs and incidence rates by ten year ape 

groups for the two ETS exposures o( antereat-years frved with a smoker 

and years worked with a smoker--are presanted in Tables 5 .7 and 5 .8 

respectrvely . There is an ncreaserd risk for age, however, the lacsc ot 

sufticaent cases prevent a carefui assessment of trend across passNe 

smokinq exposures . 

106


TA[1LE 5.7 A1kc.rf.UXl - CURREMT NOM-SIAOItER3 

tuFx) CANCER 4»77-1sW) 

D191RIOl1TqN OF iNC1QCMT (',1lSfs . PERSON 1IEJIf1$ JtPdO WClDEFICE RATES ®Y A(1E (DFFOUP 

M1D YEARS LIVED NFlR1 A SA/OttER 

FEIMLE 

A0. 0ra+' 

Cas.fl 

Pason y..n 

YEAFR9 LIVED MNTl1 SMOKER 

NDM 1-10 YEMR I I • yFpJL1 

Rwl 

10.000 PY 

Caa.sl 

Prrson y.rs 

tirW 

1D.000 PY 

Cas.y Fl.1N 

Pr.on y.rs 10,000 PY 

26-31 0 $36 0 00 0 243 0 00 0 3" 0 .00 

35-44 0 1671 0 00 0 420 0 00 01149 0 00 

0 

J 

45 64 

6594 

0 2617 

0 329Y 

0 00 

0 00 

0 947 

0• 072 

0 00 

0 00 

016219 

17?6! 

0 00 

4.41 

i6-74 1' 2687 3.72 0 677 000 11791 6.6e 

75-04 1 139! 7.16 0' 254 000 o m 0.00 

25.54 1 340 29.41 0' H 000 1 169 92.02 

Total 112647 2.37 0J202 0 .00 10171 3.9? 

MSLE 

Aq. (kow 

26-31 0 382 000 0 102 0 00 0 142 0 00 

3544 0 960 0 00 0 264 0.00 0 379 0 00 

4554 a 2109 000 0 495 000 0 77! 000 

5564 2 2371 8 _44 0 403 000 0 fS5 000 

65-74 0 1683 0 00 0 311 0 00 2 596 3359 

75 64 3 •70 34-17 0 il 0 00 0 204 0 oo 

8594 0 212 0 00 0 s 0 .00 0 11 0 00 

laa/ 8 a61s 6~0 01724 000 23107 s44


9 s 4888288 :• 

oooOeoo .i 

I 

I 

fi =ow p - 

10 ~ N 

OOOa%-Oa - 

888 t 888 ,It 

00004000 - 

000 :.000 - 

88888-8 Si 

O00OI4111g W 

i 

O O O O--N • 

8888888 8 

O O O O O O O O 

h 

eooeo00 0 

9888988 s 

O O O O OAO . 

~ 

b O O O O N O N 

9889328 A 

ooo .^ - O . 

i 

O O O N N -O q 

Tf = T S W S mi 7 W V n mmiz S g 

a 

~~ RAM" .. 

ioe

l 


Th .re w.re no casas ot " canc.r for *Vw saa an u» subjects who 

had liv .d for 1 .10 yean with a arTwka}r . For males tRere were no cases 

among ttiosa who had workad eleven years or more with a smoker . 

Four of the tfvrieen cases ocourred among form .r smokers aM of whom 

smoked more uan 9an pack years of cs9ar .des . In a s»afied analysu . 

adjusting for aqe and aex. 1lye rate ratio of " cancer among those 

amoknq more tfun trn pack yaars compared to tllosa who wae non- 

smoke+t was 2s1 (95`h C .f . 0.T8-1020, p-0 .0fs). Cons.vwntly, past acavvs 

smoknq .xposwe was tr.al .d as a ooMeurx3er and contralNd for by 

suatdication in addRional artafysls. 

The results of stratified anaryses for sefected expostue factors 

controlRr.q for age and sutaocts past srnokin9 status ar* presented 'en 

Tabre 5 .9 for fernales and Table 8 .10 fer males. The diNerances in the 

cnrde RR and adjusted RR wxficate sortw confounding due to past actrve 

smokinq arKVor age difl.rences n tM popufation and therefors tr~e 

adjusted summary rate ratios are considered as unconfounded by tne 

subjects pazt smoking status or aqe . For females who had Iived eleven 

or more years with a smoker as compared to females who had newr 

tived with a smoker the rate ratio of (unq cancer was 1 .16 (95y C.t. 

0 .20.6 .61) . For temahs v.tw Rad worked eWven or rror• years vntth a 

smoker the correspondinp nte ratio was 1 .47 (95', : C .1 . 0 1 5- 1 A 06), 

109

VsV 6soG CsoZ 


T11[f1.E 5.9 

F .c1a iwdt ' Castsl 

Ptrsort Y.rt 

/Y13M0(3 - FE/MLES 

AO.A/3TEO RAIE FiAil03 .(F1FZ1 OF IIXJO GUVCEfl /ttT7-111t?) 

FUR 9ELECTEO E]0'OSl1FZE FACIORS 

JaW 

10 F'Y 

Cnd. 

Fni 

Adpsltd 

fvl- 05% C-i. ) 

Ywws Uvod Norr 3 12ttt 23s RN. q.l. 

.Nh Snak.r 1-10 ywt 0 3301 0 0 00 0 00 

11 • lr.rs 34213 365 1 .56 1.16 (0.N1-661k p•0.a 

Ywrs YVoa1ad Non. 413161 299 RN. RsF. 

.rAo $rtnlow 1-10 ys.t 1- 6602 172 060 103 /0.11-10.11) 

-11 • "art 14670 214 0.7s 1 .47 (0.15-11 .06) 0•0.11t 

o lbut d 0-160 1 0273 16! FtN . FIM. 

®widw 161-3000 013421 2" 1 .t7 1 .7, t0 .20-1625) 

> 10 ppiw > 3000 1 0[3S 216 1 .36 0.90 10.05-16 .t3) p- 0.t0 

tburs d 0-100 1• 632t 1q RM. FiN . 

TSP 101-7000 .•190'7t 907 1 .63 1 .25 (0.14-11 .2M 

> 200 ppw > 3000 1t Sl66 168 0.n 0.69 (OVi-s.t1) y•i-a 

Eductpiaft mu.'s seteem 3 9213 326 W/. pd. 

CqMqt • 3 1496/ 200 0.61 1 .22 (0-2f-8.231 V o 062 

Ba/a-Carotwi. FiOA 2 t590 m F1N- RtF . 

Ind" FhdM" 3 7197 417 . 1 .71 111 (0w-t0 .ts1 

Low / 02" 121 0 62 035 M 07-4Jtl 0-01/ 

DtscsopMUNS n csSSS arM pNlsOn YlMt re dUe 10 

nnsw+q afus n sposur . /saor. Tald 3uANcH - 4 .024 

• Raeft p.. I m+on p.. .on pwt Cancr Cass - 6 

- }AuMtl 14wn.1 surwrnarY mtt wbo (fMII-t4 /m aqt i smokr+0 stsAvs Tola/ Psrson Yws - 2t .100


3AULE 5.10 JWtsMoo - wIAt.Es 

AI7AISiET) F6iTE TTAiIOS (1tli) OF LUPI(I CANCER {1677-10rt2} 

F .ctor L.vsb ' Cos" 

Paaon Ysrs 

FOA SELECTED E)fPQSi1RE FACTORS 

• F~td 

10 PY 

Cnd~ 

FiR 

la~usMd 

F1R" (ti6X C.C) 

Yoms Lov .A Non. 6V723 673 Fi .Q . R.f . 

wAr Snde.e /-10 years 01729 0 000 0.00 

it . 1 .ars 21123 640 1 .12 1 .i7 (0 .21-b.{1) P∎064 

Y.rs WrJrt .d Mon. 517m 625 p .t. R.t . 

.MU, 8woko. -1-10 Yamrs 23159 633 1 .01 1 .72 (0 .3 T-0.01) P- 0.3lS 

11 . y .ars 034.10 0 000 0.00 

Ftmws d 0-160 0 3S0! 

Oririnl 1e1-3000 47429 

> /0 Ww > 3000 32942 

ltaxs ml 0-100 !S3M 

1SP 101-3000 3EOS4 

> 200 Ppm > 30m • M/• 

Edacatian NiQY+ 8chool 3 3221 705 Tt'sf . Fisl. 

CoM.p. • 39692 310 a3T1 O.i6 /0.i7-3 .77) P-0.02 

BolaGrgWrw F1-gA 14114 243 SiYt . ROi. 

Ind+r Med:um 3101* 746 3 07 .1.61 (0 l1-9$16) 

Low 25302 377 t .55 1 .116 (0.ti-21 .73) p-0 .23 

DiStrlpanC.N n ta"s Wd DMfd7 yMmvt aee l1ue lkx 

mnsng vaiwt n .rpaturs l .c6i.e laUt Sub»cts - 2 .261 

. Rm per I aciron p.rson yeart Cw+c .r Caset - 7 

- AAx*c1 FRs .nSloi tunwnuy 1lt. iaao iRR)-&q ta eyes t sr.rokws0 tiafui 7,ta1 P~wsan fiurs - 13.A55


Srmlar resutts are obs.rvsd n Table 5 .10 for t:he male cohort . There cs 

a slight ncreased nsk for subjects who lived eiew,n or rtwre years wrth 

tl srnoker as compared to thase wtto had not hvtd with a srrwker, 

RR R 1 .17 (0 .21-6 .81) . For ETS •xposur• at work the raie ratio of lung 

c,ancer rn males is 1 .72 (95% C .l . 0.33-sa .0d) . Since we tuv .' vcry few 

cases the concht,ortat maximum tkefihood RR estimate and the exact rn+d 

probabltity brnorrwal confdence ntervais were also calcuLated and the 

rsutts are detaied in Table 5 .11 . TTwse resutta aue simiiu to the 

0.1atuf•Haertazei stsatifi.d anstysis . 

5.3 SUMMARY 

In both populations anah/zed tfWe appears to be a positrve eftect Of 

passrre smoking exposure with the outcome of lung cancer . Each of the 

adjusted measures of eftect for aD the ETS variabMas atxyw a positrve 

effect for expowe . However, the maQrviude of thatt effect vanes 

dependng on the cohort observed and the pyrticutar exposure vartable 

used . For both sexes n the AHSMOG cohon the reaults indicate ttut 

workng with a smoker has a gruter Nisd on " cancer than living 

wnh a smoker . However, the resulis shouJd be wuerpreled cautiously 

because of the small number oi casss that occurred n both populations . 

Further dacussion of the resutts ue prasented tr : t1ie finaf chapter . 

112


TAaIIE f.tt 

MiS4Ot] • UAJCi CJJ1CEFl 

` AD,It131® RATE RATIA3 FOR VAJiY1NCi YEARS 

Jm TYPES OF rA33tNE f11fM10 DO•OSt1RE 

rammw an+oM F.n>tM" 

E,pos,r• C.saPl RR ,'llOx On" 

Ysw tiwd 

sh SrMOrar 

td" 

Crm+PY RR MSx C)•°' 

/ioni 3'i'sltl 

0 030, 

AM . 

a00 

Llna 

a'1 T24 

aa 

0000 

„ • 1 7219 , .22 10-W .lil 

o•0 .a 

U1YJ 1 .1t (0 154 74) 

p•au 

Yan Wrated 

.iW Smok.r 

No" 4,3161 fiM . L7*6 Rrl 

,•t0 1 SA02 t .0t Va04•9.091 21151 1 .68 (0 .72-L11) 

„ . , 4670 , .34 (0 05-126b) 02420 0 .00 

o-0.7s 

v-o3S 

• Cmowrw mazarusn 6t .wuroa arm.fa aa aA .qua,.a r« ps n.o pass 

Wr+ok ..fl ass,• 

AAa vrowwry (M .w,«,) e .uoen.+ cc.,Fd.C,cs ".wW 

113


3

Fontham, E .T .H ., Correa, P ., Wu--Williams, A ., Reynolds, P ., 

Greenberg, R .S ., Buffler, P .A ., Chen, V .W ., Boyd, P ., Alterman, T ., 

Austin, D .F ., Liff, J ., and Greenberg, S .D ., "Lung Cancer in 

Nonsmoking Women : A Multicenter Case-Control Study," Cancer 

Epidemiolocry, Biomarkers & Prevention 1 : 35-43, 1991 . 

Fontham, E .T .H ., Correa, P ., Reynolds, P ., Wu-Williams, A ., 

Buffler, P .A ., Greenberg, R .S ., Chen, V .W ., Alterman, T ., Boyd, P ., 

Austin, D .F ., and Liff, J ., "Environmental Tobacco Smoke and Lung 

Cancer in Nonsmoking Women : A Multicenter Study," Journal of the 

American Medical Association 271 : 1752-1759, 1994 . 

Another American study was first published in 1991 by 

Fontham and colleagues, as a preliminary report on a case-control 

study of women in five U .S . cities . For all lung cancer cell types 

combined, an odds ratio of 1 . 34 (95% CI 1 . 03-1 .73) was reported for 

those women who reported that they were ever exposed to ETS in an 

occupationall setting . Fontham and colleagues (1994) recently 

published a report on all five years of the study . They present a 

"crude" riskk estimate for workplace exposure of 1 .12 (955~ CI 0 .91- 

1 .36), which changes dramatically after adjustment for a number of 

variables to 1 .39 (95% CI 1 .11-1 .74) . The magnitude of the change 

following adjustment is much more pronounced for the workplace risk 

estimate than for the other risk estimates in the paper . Moreover, 

the upward increase after adjustment_is suspicious . Fontham and 

colleagues do not address this apparent discrepancy . 

al . ., 1994 report : 


Additional criticisms may be made about the Fontham, et

• Despite the study's use of cotinine to assess current tobacco 

use, the authors acknowledge that misclassification of ever 

smokers as lifetime never smokers is "problematic" because 

there is "no biomarker of lifetime tobacco use ." Moreover, 

only slightly more than half (54%) of cases had cotinine 

determinations . Thus, not even recent active smoking was 

excluded for nearly half of the cases . 

• While the authors stress that their study is a multicenter 

case-control study, if the characteristics of the study 

population are examined, it is seen that the vast majority of 

cases and controls come from two areas in California (Los 

Angeles and the San Francisco Bay area) . Yet, the authors do 

not indicate that air pollution, which has been suggested to 

be a lung cancer risk factor, was "adjusted" for in their 

analyses . In fact, the authors provide no breakdown of the 

data by study center, and it is not possible to ascertain 

whether the reported risks were consistent across the centers . 

Heterogeneity in the data among study sites would argue 

against combining the data as was done in this paper . 

• Among other potential confounders that were not considered in N 

0 

the analyses is dietary saturated fat intake, recently N 

~ 

reported by Alavanja, et al ., to be associated with relative ~ 

Ll 

risks as high as 6 .0 to 11 .0 . The risk was highest in ¢, 

r1~h 

nonsmoking women with adenocarcinoma ; over 75% of the cases in n 

0 


the Fontham, et al ., study were adenocarcinomas . Alcohol 

consumption, another potential confounder, was also not 

mentioned . Recent studies have reported that smokers, and the 

persons living in their households, are likely to consume more 

fatty foods and more alcohol . 

• The presentation in the Fontham, et al ., study does not 

provide data for the possible associations between diet and 

other potential confounders and lung cancer . It is thus 

impossible to judge whether fruit and vegetable consumption 

was associated with lung cancer risk but not with smoking 

status, or with smoking status but not with lung cancer risk . 

The reader must take the authors' position that the factors 

were not confounders at face value, without the opportunity to 

examine the data . 

• The "adjustment" of the reported risk estimates is difficult 


to interpret, as the adjustments take into account both study 

design variables (e .g ., subject age) and potential 

confounders . It is not possible to determine what might be 

affecting the adjustment . In particular, the dramatic upward 

shift (1 .12 to 1 .39) in the risk estimate for workplace ~~ 

~ 

exposure is puzzling and surprising . The shift is opposite N 

~ 

the direction expected, and is of a magnitude unlike the other ~ 

~ 

adjustments in the paper. ~ 

~ 

M'i'

• The study population characteristics also reveal that over 70% 

of cases and controls were aged 60 or older . This calls into 

question the accuracy of childhood exposure estimates provided 

by these women, who were asked to recall parental smoking 

habits of more than 50 years ago ._ 

• Furthermore, the socioeconomic and educational composition of 

the study population argues against generalizing results 

reported from this study to the United States population as a 

whole . The majority of cases and controls were drawn from low 

socioeconomic strata : more than 40%- had household incomes of 

less than $20,000 . In terms of education, one-third of cases 

had no more than a high school education . 

• The conclusion stated in the abstract of the paper - 

"Exposure to ETS during adult life increases risk of lung 

cancer in lifetime nonsmokers" -- gives the appearance that 

the reported results are applicable to both men and women, 

when in fact, only women were studied . 

• Fontham and colleagues neglect to discuss the available 


workplace data from other spousal smoking studies . Of 

particular interest is the notee that several large recent 

case-control studies (Janerich, et al . ; Bro4mson, et al . ; 

Stockwell, et al . ; Wu-Williams, et al .) have reported results 

for workplace exposure that were not statistically

*-qaIVI---I 

significant . Fontham, et al ., should have put their data in 

context . 


1 

Environmental Tobacco Smoke and 

Lung Cancer in Nonsmoking Women 

A Multicenter Study 

El zabeth T . H Fontham, DrPH, Pelayo Correa, MD ; Peggy Reynolds, PhD ; Anna Wu-Williams, PhD, 

Patricia A Buffler, PhD, Raymond S Greenberg, MD, PhD, Vivien W Chen, PhD, Toni Alterman, PhD, 

Peggy Boyd, PhD . Donald F Aust n, MD, Jonathan Liff, PhD 

(3toctiv. .-To determine the relative risk (RR) of lung cancer in lifetime never 

smokers associated wit environmental tobacco smoke (ETS) exposure . 

Design,--tviutticenter population-based case-control study . 

Setting .--Five metropolitan areas in the United States : Atianta, Ga, Houston, 

Tex, Los Angeles, Calif, New Orleans, La, and the San Francisco Bay Area, CalK . 

Patients or UtMr Pa rtlclpants .-Female lifetime never smokers : 653 cases 

with histologicalty confirmed lung cancer and 1253 controls selected by random digit 

dialing and random sampling from the Health Care Financing Administration files 

for women aged 65 years and older . 

Main Chltcome M .asur. -The RR of lung cancer, estimated by adjusted odds 

ratio (OR) with 95% confidence interval (Cl), associated with ETS exposure . 

Resutts -Tobacco use by spouse(s) was associated with a 30% excess risk of 

lung cancer. all types of primary lung carcinorrla (adjusted OR=1 .29 ; P< .05), pulmonary 

adenocarrinoma (adjusted OR=128 ; P< .05), and other primary carcinomas 

of the lung (adjusted OR=1 .37 ; f~ .18) . An increasing RR of tung cancer was 

observed with increasing pack-years of spousal ETS exposure (trend P= .03), such 

that an W16 excess risk of lung cancer was observed for subjects wftt180 or more 

pack-years of exposure from a spouse (adjusted OR=1 .79 ; 95% CI=0,99 to 325) . 

The excess risk of lung cancer among women ever exposed to ETS during adult 

life in the household was 24% ; in the workplace, 39% ; and in social settings, 50"k . 

When these sources were considered joint)y, an increasing risk of lung cancer with 

increasing duration of exposure was otuerved (trend I= .001) . At the highest level 

of exposure, there was a 75% increased risk. No significant association was found 

between exposure during childhood to househoki ETS exposure from mother, father, 

or other household members ; however, women who were exposed during 

childhood had higher RRs associated with adult•Ilfe ETS exposures rilan women 

with no cNldhood exposure . At the highest level of adult smoke-years of exposure, 

the ORs for women with and without chikihood exposures were 3 .25 (95% CI, 2 .42 

to 7 .48) and 1 .77 (95% CI, 0 .98 to 3 .19), respectively, 

C, wianai IMUtulg ta 

Occup,tovU sat .ty and HeaNn Cr+crnatut owo 

of Autt~ a nov, wrtn tM Orapon F4atm D-san, 

PoruanC 

a.wrru r.a, .st: to l.wrsun, sur, urvv«,M kMdrcai 

Gna+ D.partm.nt of Patnaogy 1901 P.raao St . 

N.w. OMU,¢ U 70112. 1393 (D+ FonUurn) 

IN JANUARY 1993, the US Environmental 

Protection Agency (EPA) issued 

a report on the reapiratory health effects • 

of paaaive amoking in which it concluded 

that environmental tobacco smoke (ETS) 

is a human lung calrlnogen, responsible 

for approldmately 30001ung cancer deaths 

per year in US nonamokera' A total of 30 

epiderniologic studies conducted worldwide 

were included in the EPA risk aateasment, 

including 11 studies conducted 

in the United States?-'t Of the US atudies, 

the report of findings from the fitst 3 

years of this multicenter study' contributed 

the greatest individual study weight 

to the US aumrnary relative riak (ER) 

estimates for lung cancer . 1 .19 (959o con- 

5dence interval [CI), 1 .04 to 1&i) assoaated 

with "ever exposed" to npauaal ET5 

and 1 .38 (95% CI, 1 .13 to 1 .70) for the 

highest level of spousal ETS exposure . 

The weight accorded this etvdy in the 

EPA report reflected the large number of 

tifetime nonsmokers with hing cancer 

(n-4X), as well as the study design used 

in thia caae-control study . This study was 

designed epecifScslly to evaluate the role 

of ETS exposure in the etiology of lung 

cancer in lifetime nonemokera . 

Two large US studies have been publiahed 

aince the preparation of the EPA 

teport~ Becauae t}>ese studies are aimilar 

in size and scope to our first report, 

their findings would have had a timi)ar 

impact on the summary US risk estimates 

. Brownson et ala observed no increased 

risk in the ever-exposed category 

for spousal ETS (adjusted odds ratio 

[OR)=1 .0; 95% CI, 0 .6 to 1 .2, however, 

the CI indudes 1 .19, the US summary 

point estimate . The highest exposure aategory 

(greater than 40 pack-years) in the 

study by Brownson et a] yielded an RR 

estimate of 1 .3 (95% CI, 1 .0 to 1 .7), quite 

similar to the US "high-exposwe" alunmary 

estimate of 1 .38. In the secorld study 

by Stockwell et al," the RR estimates 

are among the highest reported for US 

studies : 1 .6 (9596 CI, 0.8 to 3A) for ever 

exposed and 24 (95% CI,1 .1 to 53) for 40 

or more smoke-yeara in adulthood . 

Thia report extends the findings of 

this multicenter study on completion of 

2 additional years of subject accrual . 

METHODS 

Ihe methods and procedures followed 

in thia study have been previously deuribed 

in detaIl.' The study was & population-ba>,ed 

case-control study of hing csnces 

in rvomen who have never used any 

tobacco product- Eligible cases included 

racnoes-ropically rnnSrmed prvnary carcinoma 

of the lung (International Claaaifioation 

of Lhaenara, Ninth Rrvirion [1CD- 

9), code 162) that .vere diagnosed between 

December 1,1986, and November30,19£?f3, 

1752 JIJUA, kna 8. 1994-Va 271, No 22 Tooacco Srrnko antl Lunp Cancer-Forvr)wn tt a+ 



Y~ g (y . °' won 

n :, ~3 

I ei ;; e~~"'wo 

- o aa ~so~ - s :,ah - 0 

s fV N 

I 

2029051465 

Y!II ~~' oogo ~ ~' 

oc{c~y~ (, 

~~S~~Y~~Cs~"~ ~~°~,a~°~~~ 

~g~s~ 8 

~~ ~ E~ ~ 8°~ ~ ~E fl^°~~ 

~ 

2* 

Y 79 

y Y 

qllli'I 0 s~-~ .5d 

-s Ls

0 0 

e 

. 

0 

, 

1 

years (7`` ,6) with a similar proportion of 

controls in this age group . As noted pre• 

viousl} .,= the age distribution in this series 

of female Lifetime never smokers with 

lung cancer is older than all female lung 

cancer cases in the Surveillance, Epidemiolog}•, 

and End Results (SEER) Pn} 

gram, 1973 through 1988 .° 

The largest proportions of hulg cancer 

cases (58 .5%) and controls (61 .1%) were 

Tahite. A larger proportion of cases were 

uelf-identilled as Asian American and Hispautic 

and a arnaller proportion as A5-ican 

American (btacks) compared with convrols 

. Approaimately 42% of cases and 

38% of controls reported an annual household 

income of less than L20000 per ye.u'• 

Compared wit}t controls, lung cancer cases 

tended to have A lower level of education : 

66.35-r of cases and 52 .6% of controls had 

no more than a high school education . 

Table 2 displays the estimated RRs of 

lung cancer associated aith ever living 

aith a spouse who smoked by type of 

tobacco . A 30% excess risk associated 

with tobacco use by spouse(s) was ob- 

6erved for all histopathologic types of 

lung cancer combined (adjusted OR=129 ; 

P< .05), for adenocarcinoma of the lung 

(adjusted OR=1 .28 ; P< .05), and for primary 

lung carcinomas other than adenorxrcinoma 

(adjusted OR=1 .37 ; P= .18). 

The only individual types of tobacco asnorinted 

with sigllificantly elevated risks 

of lung cancer are cigar- and pipe-smoke 

exposure for bronchogenic carzinornas 

other than adenoc$rcinoma : cigars, adjust 

.ed OR=1 .88 and PS .01 ; pipe, adjusted 

ORtt1 .79 and P= .Q2 . 

The estimated RRs of lung cancer associated 

with pack-years of exposure to 

spousal ETS are presented in Table 3 . 

1nc:,easing risk of lung cancer with increasing 

pack-years of spousal ETS exposure 

is observed for all lung carcinomas 

combined and for the two histopathologic 

subgroups . The risk estimates are 

similar within the histopathologic subgroups 

; however, the trend is 6ignificant 

only for all lung cancets combined (P= .03) 

and pulmonary adenocarcinoma (P< .05) . 

When the analysis was restricted to selfrespondents 

only, similar estimates of 

risk of lung cancer were observed with a 

trend of increasing risk of lung cancer at 

inavasing levels of exposure (P= .03) . 

Exposure to ETS during childhood and 

adult life 5rom multiple sources was evaluated 

. The risks of lung cancer aasociated 

with household ETS exposures during 

cluldhood as a resuh of father, mother, or 

other household member amoking are 

shown in Table 4 . None of the RR estimates 

sigTtiScantly dit7ers 5rom unity . The 

association of cumulative years of household 

exposure to ETS during childhood 

with lung cancer riek was evahtated (Table 

5) . No increased riik was associated with 

Tcw. A -Auaooatron 9 .n,ran Rw.k rrt t_unq Car+c.r .rw Cntrarwod Ewosr,r* to Tooaao Smok. Arno.p 

Noaurnok,nq Wo"n' 

twr amolud Tob .coo 

c.,. . 

wo .Erpo..d 

Oic . Wt C.wt 

CswO+, 

wo[ryo . .a 

Ib . a[ Controu 

t7„A. oA 

(fdA Cl) ~~xCt~ 

All luv prCinOrtYt 

Fat7wr JWKAJ 6169/1225 0 65 10 70-1 03) 0 63 t0 67 • 1 021 

) 

Aicmu 7b624 161/1240 OC9f069,12A 1 Oi61062,t161 

o,.r no,,..nao R»n,o.rz 1311517 26411263 0 0 (0 7o- 1 z5/ 1,03 io 6a132) 

A„1y nm,,,hao r+,.rnb.r 3 77,606 aoa'12a6 0 ea to n•1 07) 0 es l0 rr1 101 

As .r»ara~~ . 

Fam.r zamae6 e6al rns 0m7to7o-1o7) 0az(ocslw 

Wn,.r 

ou, .r Ntm, . .now r,,.mom 

Any nou.4„oa ,n,mc,r 

G+.wr htelao0w cyp.: 

Fatn.r 

blo4v r 

OC»r tea0.fwU m.mOSrs 

Ayno,,..no+drr»mw' 

6aabo 10111240 0f6(070-132) 042(065•129i 

ea/ .71 t6c,1253 0 r6 to 74 .125) 0 es to 7s 1 aor 

zao-ses 806,1238 0 is to 6c-107) 0 as (0 6b 1 oe~ 

+sa1t7 6+6v12ss 0•n(05 .•110) 0calo6a1 .20( 

16/1u 161/1240 0 64 (0AD•1 65) 061 (037-116) 

2,Vtt6 YlW1251 1 0•7(071•1 .61) 1 19 (077•1 65) 

nn ;,7 .os'12a6 0e3(o6.•1aa 101to66•151t 

'AOlustetl Fot Epe rsot t1uGy er .n *tl,c.st'on . 1rvIs "uDHS Md s+qpHmenu : wumm rdes tl .tury 

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 

oo0w.n~* ax.N . 

Tae,. 5-.4aaoa.u«, sah~..n Rmk ot Lunq Cancar " ChAdhood SmokwYSars of E*OSUro Anwnq 

Nonsrrmokirlp Women (Sen•rasponoents Onty)' 

ChllOfaod tmo~Y"rs 

CtuM oR 

A4jurMd OR 

ol How».MM Eapoaurs Ca.as GontroM 

("1. CI) 

(f41. CI) 

AN kmp nrarlornu 

0 148 ... 100 100 

1•17 ss 291 asam73•1s2t oes(07s1as) 

,16 146 aas o90(07o-117) 0t6(067 .116i 

Tr.no k . 56 TrnC R.,36 

Aa«,oaaruhon>a 

0 120 ... 100 1 00 

1 .17 73 29+ oo3to67ns9 ; 0sato6slzv~ 

ae 123 .ea owro71•1sa, 0a9(06&11A) 

TrKW A, 66 

Tror1C P*< /3 

oe,.r n.aa~tycs 

0 s6 u, t .oo 100 

1•17 22 291 120(067•214) 1s2(o72•24 1, 

:16 23 aas o 75 (0 .3-t ss) o .ns (0 .7 .1 sa) 

Tr .M P. 13 Trsno Pr 56 

•Atlµx1 .0 fa .0q rscee swoy ar.a . .bucaoon, huts rp .ud+s mW a.pp+.m.nu' vnam+n rW0x dyury 

ybist.rd . lanvy hrtory 0( k.ap urxnr, r•rstl .mpaymen/ n hgr.rxx Ocayrlt.orn O(i rd,cafts a0ds rato Ci, 

oonne .no* w.rva 

increasing duration of smoke exposure 

during clu7dhood . Cku7dhood smoke-years 

were urtlawwn for a large proportion (20%) 

of the interviews with proxy respondents 

and for 6% of the interviews conducted 

with the study aubject. For those interviews 

with data avat7a.ble to alclilate 

snwke-years, 54% of proxy respondent 

interviews ve 88% of direct study subject 

interviews reported no exposure during 

etu7dhood . The data presented, therefore, 

are for analyses restricted to self-respondents 

. No differences were ob6erved by 

pathology review ttat•us ; dietary cholesterol 

intake ; level of the fruits, vegetables, 

and aupplemenul vitamin use index ; age 

group; or educational attainnlent, Black 

study aubjert .e had a twofold elevation in 

risk ln the highest exposure category, and 

Alr'ans showed twofold reduction in risk 

at this level ; however, these two point 

eatirnates did not signi8cantly differ . Re- 

stricting years of ETS exposure during 

cht7dhood to those from the mother ytielded 

similar nonsig'rti6cant trends . 

Table 6 presents the estimated RRs 

aaaociated ait} : adult ETS exposure (ever 

exposed and years of exposure by in(b- 

.idual rotuces during adldt life) . Elevatiorw 

in risk are associated with increasing 

duration of exposure at home (trend 

P-.11), on the job (trend P= .001), and in 

social settings (trend P= .002) . TT1e inereased 

risk of lung cancer among women 

ever exposed to ETS during adult life in 

the household is 24% ; in occupational settings, 

M ; and in social nettings. 60'`.~ . 

The pattern of response is aimilar in the 

two histologic subgroups ; however, the 

tests of trend are statiatucally tigtli8cant 

only in the largest subgroup, pulmonary 

adenocarcinoma 

A,< shown in Table 7, when all sources 

of exposure to ETS dtu-ing adult life are 

. 1 ,w.v,. Ju1e 8 tASa-va 27 t, No 22 Toaacco S+11oke and lug Cance{--Fc*ltnam el aI 1T35 



5m

of the study, inereased risk of hmg cancer 

from adult ETS exposure was stronger 

for adenocsrcinoma of the lung than for 

al7 cell types combined? That ffnding is no 

longer apparent with the additional cases 

of each cell type . Although the estimates 

of RR for pulmonary adenocarcinoma are 

not different from tHose for other cell 

types, adenocarcinoma of the lung is by 

far the predominant cell type diagnosed 

in women with lung cancer who are lifetime 

nonsmokers, and oo the ef5ects of 

ETS exposure may be particularly rel• 

evant for this histopathologic cell type .' 

More than 75% of the cases in this study 

were diagnosed with prim.v-yy pulmonary 

a.denecarcinoma, twice the proportion of 

adenocareinoma of the lung diagnosed in 

all US women without regard to smoking 

history: 37% among female lung cancer 

cases in the SEER program .° In other 

studies of E'I5 in female nonsmokers in 

which histopathology was reported, adwnlocstrcinoma 

comprised 60 K or more of 

nll cases in six of nine studies .L'"'6' ' In 

the other three studies, the proportion of 

udenocarcinotna cases ranged from 43% 

Ro 549E ." 1' Differences in the physical and 

themical properties of sidestream smoke 

compared with mainstream smoke, including 

the distnbution of the vapor and particulate 

phases and the concentration of 

Imov.-n or suspected carcinogens!' combined 

uith ditferences in inhalation, nasal 

vs oral, may yield a higher proportion of 

peripheral adenoatranomas .u 

Ddisclassification of disease status was 

minimized in this study by the eligibility 

rriteria (microscopic diagnosis required) 

and an independent review of diagnostic 

ataterial that was completed for 85% of 

the cases . The amall proportion of cases 

found ineligtble by independent review 

may result from the populat.ion•based tumor 

registry affiliation of four of the five 

study cent.ers. The consistency of the findings 

w-ith and without nonreviewed cases 

supports the contention that the study 

results were not measurably altered by 

incluaion of ineligible caees . 

Misclassification of eversmoker6 as lifetime 

never smokers is more problematic . 

'I11e objective of this study was to evalu• 

ate the risk of lung cancer in women who 

had never smoked . At present there is no 

known biomarker of lifetime tobacco use . 

Cotinine, the major metabolite of nicotine, 

is the most widely accepted biomarker 

of current (I to 2 days) tobacco 

exposure and is useful for distinguishing 

current active 6wrukers from current nonainokers 

.'"' The proportion of reported 

nartsntokersin the present study with a 

cotininelcreatinine concentration above 

100 nghng was 1 .9%, the same proportion 

vrith a concentration above 100 nghng 

obeerved in a 10-country, multicenter 

study of self-reported ETS eupo6ure" 

.lAMN, Jwte 8, 1 ;W-VO( 271, No 22 


TaM. 7--Aauoaanon gfiww Rrk 0t Lunq C .nar sna AdAawod S+rwk.-Y ..n d Expu>r. Amx,q 

/lonunoWnO wom.n• 

~~ 

~ cn,a. oa aeWs+ .e on 

c., .. oo araft tts+. Co (ss+ cu 

aJ1 t.,Rq C.rtMnww (Aw IL.poneenb) 

0 ,6 tte 100 

1•11 74 299 076(050-116i 

122e 136 307 111 (0755163) 

29-47 163 3W 12 .(0eA . 1 921 

a+6 163 265 1 $10 .03•2 .23)1 

Adenoc+rdnae . (AM OLepen6r++tt) 

Tnntl fi . 0001 

0 36 11e 1 .00 . . 

1•11 6. 239 0 7< (o 46L1 19) 

1226 1io K7 1 .17(076•1 e1) 

20.r7 112 304 121 (07'6•166) 

n46 130 M 1 .61 (1 .0b217)1 

TnM A. 0002 

()Hu . N/lqoiopkal Typ.s (N( /I+spondvrtn) 

0 12 118 100 _ 100 

100 

062(052•1 .29) 

112(o7S17o) 

135(oe420a) 

1 .74 (1 14-2 65)1 

Trtntl P. 0001 

1,00 

074 (0 .•u .1 23) 

1 .15 (o 73-1 tJt 

119(0e1•20a) 

1 77 (112•2 6011 

Tnrd H. 0001 

20 239 0e2(039-174) 117(052•262) 

122e 26 307 090(o4t-162) 1001oA621e ; 

24-a7 41 304 1,33(067•261) 1 .58(076331) 

:i6 13 265 1 .Y.!(061•216) 1 .76(063.375) 

Teur.tl P. 12 TrmO W 05 

Aut u" C«otr,a>re ".w~onse(w or+ly) 

0 30 11e 1,00 1 .00 

;.11 53 238 00E(051•15A) 079(0W 42) 

12•2e 103 306 1 .32 (06t•210) 1 20 (0'A•1 94) 

2D-~ 7 110 304 112(09ti223) 14+(ot4231) 

:a6 105 265 1,56 (0,9cS•2 47) 1 .67 (1 B3•2 70tt 

0 

1•11 

122e 

29-47 

:i6 

AA.norarcMm .n . (s.n+wva,Wa o„H) 

TMr+tl P . 002 Tnrb h 0006 

23 11e 100 . . 100 

A1 236 0 66 (o 5} 1") 0 D 1(0 46,1 , 37) 

a6 306 1 46 (o 99•2 45) 1 31 (0 77•2 22) 

62 304 1,36(0f.1230) 139 to624 361 

91 265 1 76 (1 .06-2 02)1 115 (7 0P3 15)1 

Tnnd Fr,001 7rOrd 0. 0005 

om« rrwo1optu( Tw« (aas4. .PONOOP" onM) 

0 7 116 100 . . . 1 00 

1•11 12 236 0a5(031222) 0 91 (0 3A•2 .5) 

12•2e ls ao6 o 93 (0 .33•2 06) 062(031•216) 

29~7 ~ 304 1 55 (o 66•3 65) 1Ft (0674 03) 

14 2a5 0 69 (0 .35•226) 1 12 (o 42r2 96) 

TrMO R 49 Twntl P= 32 

'Atltuttod br p! . fTp* autly .rN *dY'.11qn. hUR{ . vpartbltt . >/Rtl uuryp+rmfnW VumA r1Wx bftay 

dw4surd, s.mry trstory d Mq umr, .nC .mpay*r»m n r,pn-rwK aoa.prba>t OFi rdcws oilos reeo . CI . 

oon6cs.np rr .naW 

tp< .os 

A higher proportion of controle than 

cases was exc]uded from the study s6 a 

result of elevated ooncentrations of urinary 

cotinineJcreatinine, 2.3% vs 0 .6% . 

(',ases were klenti4ed at ho6pitals, and 

aaeedng of medical records and physieLUU 

about the patient's current and past 

use of tobaxo preceded the screening by 

telephone and at the interview for all 6Ux1yy 

subjecw .'Itiia procedure may have eliminated 

some curnent amokers from the case 

series who would have been inclined to 

self-report as nonamokers in an interview 

format. Alternatively, some cases who 

would miareport smoking status may be 

less likely, because of health status, to be 

actively antddng and less &ceh• to be revealed 

than healthy, free-living controls . 

Other data suggest that lung cancer 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) 

12•26 41 97 0 91 (0 S2•1 58 0 00 (0 43-1 46) 86 2U2 240(1 .06-530) 

2947 

5_4 97 1 .20(071•20-4) 1 .16(06S-20e) E5 204 229 (1 .0+507) 

246 _ _ 53 90 1 .45 10 a5419) 

1 .77 (0 .96-J 19) 94 ia2 214 (129-62!) 

Trsnd Pe 04 

Tr.nd P. 01 

Aa laA4 Cwskro~ v. CsnaW (9+M+.pondwxs Only) 

0 Z3 71 1 .00 1 00 , 5 44 1 00 

Tisntl P.001J 

1-11 23 90 0 79 (0i1 .1 .52) 066 (0 54 .1 38) 29 137 1J6(066-510) 

12-2! 26 97 0 99 (0 47-1 67) 064 (032•12e) 69 201 J02(115-793)t 

2"7 i 97 1 15 (0 63-2 10) 104 (054-196) 67 2w 2 69 (1 10-7 59 )1 

za! 31 Do 1,20 (0 64-224) 1 14 t (0 69-2 60) 70 192 J~9(129-669)t 

Tmnd P. 26 TrMOR 17 Tr.ntl P. 004 

! 

'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 

axupaoon Oq u o,ca .c o0as rac0. CI . oonhb .na nunnl 

tP< 05 

tF< .01 

Refusal to protiide a sample was similar 

among Liv-ing cases (19%) and controls 

(17%); however, because of illness and 

death, a higher proportion of the total 

subjects in the case series had no cotinine 

measurement . Of study subjects for whom 

no sample was available, 63% reported 

ever having lived with a spouse who 

smoked ; for study subjects with cotitilne 

detesTninations, 639(c of eligtble women and 

68% of excluded women reported ever 

having spousal ETS exposure . 

Analyses using a lower cut point (55 

mg/ng) for exclusion based on urinary 

cot.171ine concentrations provided slightly 

higher estimates of risk associated with 

ETS exposure, but the differences have 

little or no effect on study conclusions . 

Compared with recent large US studies, 

the proportion of proxy respondents 

for lung cancer cases in this study was 

small : 36.9% compared with 65% in the 

study reported by Brownson et al" and 

67% in the study by Stockwell et al" 

Nevertheless, it is important to evaluate 

wheth,er the 5ndings differ when proxy 

respondents are excluded from the analysea 

. The only appreciable difference was 

noted for childhood exposures . Of those 

interviews with proxy respondents, 31% 

were conducted with the study subject's 

spouse and 48% with an adult offspring 

of the study 9ubject. These individuals 

had lived with the study subject and 

shared life experiences during the study 

subject's adult life, but not during the 

study subject's childhood years . The opportunity 

for misclassification of exposures 

is greater, therefore, for childhood 

exposures . The lower reliability for child• 

hood exposures compared with estimates 

of exposure from a spouse has been noted 

previoualy!0"1 The consistency of finding3 

for adult-life exposures in the total 

175E J.UA6.. Jtx1e 8, 1994--va 271, No 22 


series and among self-respondents only 

suggests that systematic misclassification 

by proxy respondents for adult-life 

ETS exposures was minimal . 

The inconsistency in the literature with 

regard to the association of lung cancer 

with ETS exposure during childhoodl' 

"~123' may stem from the limited 

power of many of these studies, as 

well as difficulties in recall of distant 

events and/or incomplete knowledge by 

proxy respondents . The effect of each of 

these factors is likely to vary among different 

cultures, as well as by the proportion 

of proxy respondents in any given 

study . Failure to find an independent effect 

of childhood exposure in case-control 

studies might result also from the latency 

period of lung cancer and the age distribution 

of female nonsmokers with lung 

cancer . Lung cancer arising as a result of 

childhood ETS expoaure would be expected 

to occur relatively early in life . 

Even with a latent period of 30 or 40 

years, these casea would be young>er than 

60 yeara at the time of diagnosis, aad 

such caaes comprise a small part of the 

total case series. No differences were observed 

in this study, however, when risk 

assoriated with 9rnoke-years of exposure 

during childhood was examined for subjects 

in the case and control groups who ' 

were younger than 60 years compared 

with those 60 years of age and older . A]though 

no independent effect of childhood 

exposure was observed, such exposure 

appears to modify the effect of aubsequent 

ETS exposure during adult life. 

Twofold increaaea in risk are observed at 

all levels of adult exposure for subjects 

who had any childhood household exposure 

compared with those who did not . 

Individual nutrients and micaonutzienta 

associated with lung cancer were included 

100 

1 93 (0 99d .a6) 

24J(1 .07•551)t 

294 (1 16-601)t 

325 (1 42•7 46)S 

TnnO P. .00o6 

in preliminary analyses . The final model 

includes an index that captures the intake 

of both dietary and supplemental antioxidants 

and a variable for dietaryintske of 

choleaterol adjusted for calorsea . In this 

study, high intake of hu.its and vegetables 

and supplemental vitunins is asaociated 

with derreased risk of lung cancer, and 

dietary cholesterol is associated svith incrv.a9ed 

risk. Although it has been suggested 

that low intake of csrotenoids or 

>}tritb and vegetables and high intake of 

dietary fat are potential confounders of 

the association between ETS and lung 

cancer!4 this was not observed in our atuiiy 

or in the recent report by Kalandidi et 

aL" In addition, similar trends of increased 

risk of lung cancer asaociaied with ina~ 

ing smoke-years of exposure are apparent 

at all levels of both dietary cholesterol 

intake and the index of fruits, vegetables, 

and supplemental vitamin use . Household 

radon >reas measured by 48-ho(ff paesive 

diltusion canisters in a sample of study 

subjecte' homes, and these scrcening levels 

in all five geographic areas were uniformly 

low and not associated with casecontrol 

atatua . These obees vations i.ndiate 

that the strong association in this 

study between adult ETS exposure and 

lung cancer risk cannot be attnbuted to 

any likely amfounder . 

A positive dobe response between ETS 

exposure during adult life and lung cancer 

risk was found .+hen individual sources 

of exposure, such as household, occupational, 

and social settings, were examined 

separately, and this pattern of risk 

was clearest when these exposure sources 

were considered jointly . The point estimates 

are somewhat higher for exposures 

in occupational and social settings than 

within households, but these differences 

are not statistically signi8osnt .'I11e higher 

TOba= Smolce and LunQ CanCm-fonUlam et sl

del 

tke 

UC]a 

of 

his 

tles 

ed 

3nd 

Ql- 

a of 

ang 

udy 

i et 

lbed 

eas . 

ual•erol 

ttvtd 

sive 

udy 

lev 

]mi- 

-Asemdithis 

and 

-d to 

estimates in the former settings may retlect 

etunce, some recnl) bias, or the potential 

for a larger nt.lmber of smokers 

and smoke exposures in these settings, 

Workplace ETS exposure has receivedless 

attention than domestic ETS exposure 

in studies of lung cancer to date ; 

however, monitoring of ETS or its conatituentL 

in workplace settings has demonstrated 

detertable markers of ETS by 

penwnal air monitoring and biomarke .ls 

with average concentrations similar to 

residential levels but writh higher maximwn 

v»lues .l In a etudy of workplace 

ETS, the correlation between number of ' 

smokers encountered during a workshiil 

and personal sampler nicotine concentration 

(micrograms per cubic meter) was 

0 .'6,.`y (Pj cancer tn Texaa, !n : Iltull M, 

CoeTta F, K111.LwQ CanCeT' Calllei and PreUentsm% 

. Ne- York. NY . VertaQ Chemu lntern.tional 

lnc~ 198483-99, 

{. Chan WD, Funa SC . Lung cancer ]n rwa+moken 

ia HostgKortt In: Grundtnann E, ed Caue+ Campatqn, 

Vl. Caner. Epdernwlapy Stirtt;art, Germany- 

Gauv Fischer Verlar. 19EL19&2t2- 

7 . Carre. P, Fonthun E, Psekk L Lm Y, Haanrtcl 

W . P.etiv'e amold4 and katg euwer . 1-aeaa 1989 ; 

L5Ws5e7 . 

{- Gw Y, Blot WJ, Zheng W, et al, Lung eancer 

amona Chuuse women . !nt J Canerr1fl67 ;itr•604eo9 

1, GarGnkel L . Auert,arJ 0, Joubert L. lnvdutr 

ury alrroidng and Imtt cancer . a cue-eorttrd study . 

J Natl Caweer lut 1985,75 :463-469 . 

10, Gen= G, LianQ ZH, Zhant GL On the relatim, 

alup bet .+een smoking and fernale lung cancer . In : 

Aolc 1(, Hutmichi S, Tominags S, edsSmoktnq 

andHwlth Amaterdam,theNetheriands,Elsevier 

Science Publuhen, 198E :4£~3 1&6 

11. Humble CG, Samet JSf, Patluk DR . M .mage 

to a emoker and lung cancer risk . Am J Pwblic 

Healtk 1W4,77:59es-602 

12 Inoue R, Hzreyuru T Pasdve emolartQ and hrrtg 

oanorr in women ln Aoki ed, Hiumiehi S,Tornuuga 

S. ads Smokinq a+d Nealth Amatenlam, the Netheriands. 

Elsevier Soenee Pubtuhers; 198&283-285, 

11- Janerich DT, Tbompaon WD, Vanla LR, at al 

Lung cancer and exposure to tobacco rmoke in the 

hoasehold, N EKg1 1 Med 199tr323 .632-836 

14, Ktbst GC, Vlynder EL. Lung canaer in nonamoicen 

Caerer 19Bf ;53,1214-1221 . 

ls. Kahrdidi A . Kuaouyanni K, Volopoubu N, el al . 

Pe.dre arwianQ ard diet in the etwbr• of htng anoer 

amonQ nonmiokat Ca~ Ca u.ce Cowtrol. 19Btr 

1 :1521. 

1C Koo LC, Ho JH . SaR D, Ho CY . Neastaements 

of paasive amokinQ and eetirnates of htng urxer 

rlak amortg notumoklnY Chinese femtk..l+u J Canosr 

1987 :39 162•169 

17. Lam TH, Ktug 17?!, W oetK Cld, et al SmoinnQ, 

paice m o1anQ, and hutologtrul typee in hwq atscer 

trt Htxtg Kong Cl»nae vornen . Br J Cawcrr, 198'116 : 

E73-b75 

I& Lam V+'K. A Cltxicd ard Ep6demwlopieal Sts+dy 

c/CarcinornaoftkeLunptnHonpKonp HongKoap- 

Unh'vsity of Hoeg KortQ I965 . 7heda, 

19 . Lee PN, CLarnberiain J, Akerwn YR, Retation 

.ltip of paaaive tmokinQ to risk of hutg cancer 

and other emokmg-as.ociated dueues, Br J Caeeer 

19B6 ;Si97•]05 

!6. Liu Z, He X, Chapman RS . Smoidrty and other 

risk f.aon for hutg cancer tn XtrrtweL Chins . l.t 

J Epitemiol. 1fle1Z-26-S1 . 

21 . Per.hagen G, Hrubec 2, Sveruson C . Pt.aive 

aatoidltt and iutte cancer in Swedish w•omen• Atn J 

Epidem wl 198-7;126 :17-24 . 

!t Shimia H, Idorislilta )i, B[isww K& et al A 

a.se-crontrol stvdy of hung cancer tn norAmsoltint 

wornen . ToAokw J Erp Med 1988161 E89J97, 

i3. BobGx T, SauJd R, N akayanu N, et al• PaasSve 

asnoMng araonQ nonarnolW women ard the rek .tionahip 

between ladoor aSr pollution .nd hutt nneer 

ksddcnce . C,aw No RtwAa, 11DU,J6 :S19S33• 

14, Bvensaon C, Pets}um G, Kkxniaxk J . Smah- 

Ir>z and peulve atnoidrtl in relation to kum cancer 

in woenen- Acta O.eol. 198MdZ;iL29 . 

T[• Iridtopottba D, Kilandidi A, Bparx. L lausQ 

eanoer and passive amoidrg , Lawert .19B33•667-668ti. 

M'u AH, Hender.on BE, Ptke HD, Yn NC. SmokisQ 

aa,d othet riak faRora for kmc anaer in wanen . 

J Nail Cawar. lsui 1985 ;74:747•751 . 

!7 . R'u-Williaau AH, Samet JH . Envirorunental 

tab.c-co mwke : exposure-reeporuu re4tioelehipe in 

•pidemiolopfc ntldiea . Ruk Anal 199(T,1tr39-48- 

2& Butkr TL, The Relatuouktp ojpausva Smok 

aap to Vanow Healtl Osleomea Awonp SnVnlh• 

Day Adtrxtuu tn Caltfomia Loe Antnles . Univenny 

of Calilornu-Loc Ano ke ; 1968 Tbeeiu . 

!!. Gar4rtkel 1 . . Ttme tmds in kc* aenec n+oeubt y 

annew mrmokm and a rwtr on prwve anoionQ 

J Nat1 Cawcr* lntt 19817B :1061-1066 

8!. Ha+yurr TCanocr tnoetality fn wicnmlang 

.ortscnwSth aa/o1miQ lw .banda based on a lar{t.ok 

eotsort "y m Japan Pm• M.d 19B4;IIh68Jd90 

11 . Hok DJ, Gillia CR, Chopr . C, Ha.nhorne VN 

Paative unolanQ and nrd areepira ory hsalth tn a 

tetseraJ popuLtion in the west of SeoU.nd. BMJ 

I>189~ t2112 7 32- Brawoe RC, Akavvt}a MC, Hock ET, Loy 

T8 . Paadve rnoMnt and 1ur1g anaer tn nonamok , 

bftjwomen, Am J Pa bltc H .a1tk 19Q=,15251 S3G . 

fL Bt«kwell HG, Goldtnen AL, Lytran GH, et a1 

Earborune.ntal tab.nv arnoke and hrY cancer risk tn 

aanetwidrc wonun J Nail Cewrr hue ICfQ8/a 417- 

1422 

34 . Haley NJ, Axelrwd CY, T11ton fLA, Va}idation 

*( seu-reported anokint beharror bioctsenucal 

an.lyca of eotinine ar,d thioeyaruu. Am J Pybl c 

FleaftA 1983 ;73:1bD4-= . 

i6- Largone JJ, Gjika HB, Van Vtmalu . H . NKa-uK• 

a1d its rnetabohtts : tadiaunmuno.uays for tucounc 

and cotittine, B a'kemittry 19T3,1r5Q2SSa36 . 

K. Riboli E, Preswn-ldart n S, Saracn R, et al 

Expoeure of nonamoldn6 vomen to en~-iralmenul 

tabac•co mwke : a ten eountry collaborative atudy . 

Caneer Cavu. Control . 1M,1'1A3-ffi2 . 

17. Jarvv NJ, Tttrrutall-Pedoe H, Feyerabend C, 

Veeey C, Saloo}ee Y . Comp.rison of tests used to 

dittulfttiah emokers from nonmsokers . Am J P~b 

1u Healtk 1967 ;77 :1435-1438, 

SL Haky NJ, Coloaimo SG, Axeb-.d CH, Hami R, 

Sepkovic DW . Bioehenval ralidation ot .elf-ropotted 

expoaure to enviratmental tah .cco smoke . 

Et,oron RestarrA 1989,4J.17i-M 

38• HoEmaltn DW, Haley NJ, Adams JK', Brun . 

aeaan KD . Tobacco aideatrum talsoke : upt,ake by 

aonmsolten, Prer M .d 19& ;1~~615, 

a Hu .txn ME . Boyd G . Boyd D . et al Psniave 

a61 saokaS on eoeartrseal aitiine Eiat~u JA![A 19eia, 

ffi7-9TL 

41 . Schkaaetmann JJ . Ca.e-Ca+tml Strdu 

: Oxford 

. !krnpn, Conduct, Analyeu, New York, N5' 

University Preu ; 1982 . 

4t KYstbatan DG, Kupper LL Margemnem H, Ep 

demsobpu Reamircklannripla ad Quowlimtur 

MdAoda Beltnatt, Calif, Lffetune LwrtilV Pubbaa, 

tims; 1962 

13- Rees LAG, Hankey BF, ltilkr BA, Hartman 

Ald, Edw=rds BK Co%cer Stafut rs Rmrsr J9'd 

tA Bethe .da• Md : National Canoer Inrutute : 1991 . 

152-V123, NIH publintion 91-Zf89 . 

44. Committee on Parive Smolmt4, Board on Enrr 

rarutsental Studies and ToodeolV•, Nauotul Reaeard, 

Cauta7 . Ent~rowrwulalTobarcoSmokr Jd~nuq 

Erpoevres awd Ataeaaenp HrohA E1Tecu v,• ..huy 

tan, DC: Natiotsal Academy Pre .s; 1996 

4& Wynder EL Goadaan lfT . Smoidne and big 

t.mr. wne tmrodved i.nlaa Erdnn usl R", 19Hi . 

k177-l07 . 

16 . Pron GE, Burch JB, Ho .ve GR. iG7kr AB The 

reliabllity of pusive amobrq kiatoeiee reporned in 

4 taae-Cont.rol study d yuatt cancer . AM J Epuir 

sRiol, 1988;127367-2'f3, 

47 . Coultai DB, Peake GT, suett JY Quealon . 

saire araea .ment of Hfetfine and rrcent expoRure to 

entironrnental tabuM arnke, Aat J Epid.niiol 

1lRP 11Cr33R-b/7 . 

46• LeNaretund L, N'tlkina LR, Hankin JH, Haky 

NJ, Dietuy patterns of fevule aawtwkrrx with 

u+d .rlthout exposure to emironmemul tobacro 

amoke . Ca .err CaY.y CoRtrd . 1991 ;2 .•11 • I6 

11. Couha. DB, Baznet JM, MeCaMy JF, Spen 

tier JD A personal moetftoeint study to a.xm 

veStpLce exposure to envirr,nlnental tohacoo 

crrqke . Am J Prb1K H.altA 199PA09hti 99(, 

i4 Brtauxnunn KD, Cox JE, Hofhcunn D Analy • 

.ia of tobaecoapecific A"•nitrosamines In tndoor air 

C.xiKO9eweau1992131415-241fi . 

-1,D1 dl 1 ,IAAAA, ,kxle 8, 1984-Vol 271, No, 22 Tobacco Srnoke and Ltrsp CarKx - Fontr am el al 175i 


I 

. 

q+ r . a-el +•.~, w•!L>.r.+w• rtr r 

t~ w+..t.n t.ro6. .% a w.w.a ., u 

Lung Cancer in Nonsmoking Women : A Multicenter 

Case-Control Study' 

[(ittbett, T . a{ . fonfham! Ie(aye Ce:enes, Arwu W W 

WIIlitml, Ptltl ltrsotds, t.a+nond S . Ctetnber}, 

t'etrici/ A&uitttr, Yi .ien 14' . Chen, rt,tt sord, 

Ton1 jkIttrmtn, Donild F . Arntin, lonathajk Uf/, 

and S Dw4ld CrrenLer•{ 

p.•p.A ~,r•. e+etA.Mer• lt..w. .•u lurr l>~+sR. W4[J Cwn 

.- abrnr tw•,w lo+u It t M f . r C v v. C I Drs+"~ 

p re+ ..ir t .! Ce•,~•,,nnr watwt V++rn~. " C~ 

tw e.+Yewr Cl1,teMd eCC)l l~ v . v. 1 C'a .mr L1.rr+, .. .. r 

terrq, trwxr t~+'r+•t. Cwr ."v Ir t, D tA .l 0••..• et 

te.+-a+o= (~ tr«-v, kM.ofve.rwrc wrrth AA.., 

e . : tiu iCtt) it f C 1 t 1 kbo v r .A+t arreR tJw.e•t•+r 

wj+tr. krcr C~r uwrre+` 1r.e~ f70)D tr A t, 

. : Cs`rrw e-V. wrt- 1.NW . CaJ~rnr M7)p 

rr t 1 ..,r AcM,-v,e{.w Crrr4p .r waK .e 

Nr+u... . 1tr,m t70)O It D C I 

Alrira n 

Tl.e alroci .tion 16et-ren etpoeurt to rmrironaw++ts( 

tob&ccm tmole end Ivnt C .ncer in fern .te Wttrmt 

non/moltri .tt t .alutted utint dau Collected durinj 

the firrt 7 tu+t of an ontoinS uk .eontrol aardt . Thit 

urSt, tnuhicenttr, poputetion•btud ttudt war 

deutntd to min(rni :e torne of the methodo(ot

,1 lsy Cerw M Mwwft.tM11,60" 


erntiuuonl and cLssrf,catron of tht h .uopttho+o~ca1 ct6 

ol9r 

Kf Reu(f ay .es Two control R oups ex+e w++h cD+on 

cancer end ont from the Ienert,t popu4tan . an neirCSed 

6ot cese•control comp.ntont Ddfetentul reutl brc.Yrn 

a+ses end co4on cancer tontrofs should bs te+m+mutd 

Nnce both `roups are umlLriy tesosrvited to rec.aU earyer 

eraaoaxrs . 

{dl S~~e of p?S f .DOSUre M+fon+utan on dttdlsood 

taposutes from a fether, mothtr, and other hosnehotd 

enemben end adult e.posuret from hutb+rdlsl, t>tdser 

household memben . and occvy4tran+l end nocul ae . 

esMV 'r oblorned br quetironrur+t The riti etsoc+sted 

vnth nposurt to 1rTS from dd(ennr tewrca enE iuusR 

dd(erent time perrod, ean be tv .tuaud 

fe! Confoundtn and C)ther Rnt rKton Rtuwe the 

ru=nwude of the m+tn ETS tlleet rt etpttud to be veu11 . 

h rr iMponlnt 7o tltt rntolctov'Ir porentylcOnfoVndtnj 

tanorc and t(feci mod,rY,nt 411111 sn , pudy w-+th a 

wfhcnnlly farte number ot eetts end eOnuols h et 

ttnhcrpated that upon complelwn of thrs ttudy ebout fA0 

utes and twrce th4t ewmbei o( controh wiA have 

p&nrctp+ted 

Thrs rtpon reprerents frndutp fro+n Nx c>rsWn ; 

t ;tudy and Mx(udet the Lrtett nurnber of fr/etrmt non• 

tmolt't vrfth iunS tencert repaned to date Thn report 

wit (th to ba tuttified {-ventht public htttth wnpon .nce 

of the tfsue under m,tsi,}ttron 

I 

Methods 

The s,udr is e popu4rion•based cese-conrrol ttudy of 

tune c .ncer rn .wor*en who ha .t ne~er t»ed .nT tobacco 

prodvrt This prr6enrv-y trpon rnctudes eeses du=• 

nosed dur,nl the hru three rer*t (Decemtxr t, 11d5 

Ihrou'^ December 31, I9S6, ol a S-yar ttudy At the 

rme o( d4) .+os s uses wert residems of one of (rvt 

nujor rnerropoLUn areis rhrouthout the tJnned Sutes 

(nclud^g Atlanta (CLt'ton Cobb Dea.tb Fuhon, and 

Gwrnnt'I countr

)IV~ r VaV'~ iM+~eKNt~+~M ~.~ w w

somommammmazzo 

as a, . ., t,.W r NON- ::k;, 


a.* 

ou. e .~ e. & .!a rrer .., ...M+w ', 

Aome i Tmuhs or mae du+ini chWhood ChfldhoorJ 

tivas defwd as thr iru 11 rears .rlie Eaye»ur$t (rom 

parents after ehit t1me , .." cia»,f,e•d as other M,wetsold 

mtmbers dunnj ad .,h ldt Dichotomous ETS e :powrn 

wtrt firtt tUmrnad Itvtr rY Re+Trl bt type of tobaccoo 

craarettes p'pr c,la•, or any of tMst tyqes of tobacto 

pose w+s est'mared at approprure by M++emrry /t ` . 

numbtr of crg+rrnes/darl, duurwn (e t, numbe, of 

ynrs e .posrd' or a comb-nat,an it 1, pack•y .arnl Pack• 

Ytt'n of ti{erette e .posure trom cht spouu arrt ca9cu• 

l4rtd by mulr'ply,nl the numbtr of packr unolced ptr 

dar b1 rht number of yte .rs the i.po%ne tenoktd e11arrnn 

wfi,k 4vrni ~,,h tht ttudy subttrt rack•yeers of tapKture 

wtrt eummed (or all r,nwk,ni tpouses of eaCh tWdr 

wbttcf 

Ont of the obtec+rvrs of thn etudy was to r-vaiwte 

the essoc,ar,on of ETS with sptcifK hmopa+holoìcel cel+ 

types of fun& cancer 7he altwrd dntrrbutron of hatopatholog'cal 

trpes prec)uded anis, mtanrntfuf ana)tsn by 

tpe0 .c cell type orht, thin adenocaremoma arnd all 

orher ceP sypt, comb~ned The reaults are presented /or 

+11 (unb cancers tomb,ned In .. 420I .nd adenoc .*cmomas 

cont,rmtd by 1+lstope's+ofog~cal reYreM (n . ={1) . 

Cates wtre cornprtd so each control lroup wnh 

reàrd to the d,vrrrbyt,on of rrle .ani co>aruur such as 

aIt educat,on sncomt ar,d race/tthn~crtr The aswcr• 

at,on of ETS tapoture w~th IUnti cancer rnk was dr ..estr 

P+td Lrst rn eont,ngeneis ubks ttratrLtd by dnrfn oe 

ump!mg .arables la`t, ract, u,.dr etnter) and eilevant 

co .ar,ates Sumrna•y adsusted odds ratw+ and tett euus• 

hcs v,ert caku4ied bt the mtthod of rvtantef and r4en . 

sre) t)J) Uncond,t,orul tog,stuc rta-tss,orn analy>•n yrrtre 

then used to ettmn+se the attocut,om by nummary ad• 

jutted odds ratros, eonfrdtnce hrnns . and (nt wxrusei 

q7 .14) . 

te.arftt 

DemoSraphic tharacneristrn !+t tasr+ and eewuroh are 

presenttd in Table 4 Casts and eontrols wert u+nitar 

evrth tnpen 6o matth,ns varubles and tnoel ieerw• 

1 raphK wr,abtes The larlest ewmbt+ of ta6n in • 1tiQ 

1141 were rts+dentt of tos Arqrln, Ootto-td Ivr eAetc 

lrom ttu San irancnto sar Nta !n . 149, )S!k) . and 

then the three t.mat(er Nudy centers h the southtrn 

Unrted Statn AtLnta tn . ai, 1 t161 ; Moutton (n r», 

p•ti), and New Oritant /n r=i . trx1 . 

The a=e d,st,ibution of tases arsd tonwoSs ts exvfoeen, 

wnh f) to 74% of tach .erKS betwten the ain of Lo 

ihrouo !1 The proponbn of otdtr .romen ws thsu {rovp 

of fenute norumalen whh kml unttr 1t hsher thtn 

...____._-. 

w.. .r «r+~~ 

r» e,,., t.+ 

rN M~ i. rwr, .' ~t".u` mf r.w~. t+e~9*~ 

- 

thai antonl •A kr+,ak kRy cantrr cyu1 t't the SEER 

irofram W4-1!!6, en wb+ch tanty 43% Mt eht Cases 

were aRtd iS or esidtr E)S1 . 

Cases tended to have a>,oR .ewfut Iorm isouse~d 

1 .co+ne an$ kss eduut on than the popuUtwn tontro{s 

P,tp a .,rnattY~ D51t, of castt$ tnd conrrob Upen+ t#een 

rf. :tiood m crt,es wr>h poputatrons of 50 OOC or tnae 

and rnt enatornY of uses and tontrolt f70% i8% ,17f+ 

for taets Colorr Cancer conr,ols and populas,e,+, cor+troo . 

tetptctrr2ly) rnrded en CArn durdy r+rasr of tM•r aduh 

Mft . The ntrnuttd r:sks of IvnS unctr In no+srnoArtq 

women astocattd w9h gve, hav,n` Ir .t•d wnh a ~t 

who tmoked are plestrtited .+Tabk S The adtusttd Olls 

and tht 1S'r. Ct are verr e+m,tar (or en tpoutio-ralaud 

eepo+ures reEardkss of controt Sroup for ali h,srotyth• 

olo{,csl tyrpes of )und tance comb,ned a 10', . srycrtau 

r, rrsk rs obur.3d lOt . 1•SI and 1,Y4 wnh coko++ea+_et 

and populat,on tontrotst For tath of tht thrte rvpt, of 

tobacco trrsaled the ORs ranged from 1 14 to 1,36 

When thr case ser,ts rs tetrrtoed to the Sit ®ulrnorteR 

adenocarca+omas conr,rmed bv h t+opa+t oto= ca~ n .+t . . 

the ast•acur,on it mort pronounced Appro .,marNr Sa% 

ekvat+ans m rnl of adenocartrnor?,as of tht Ivn= 1t s 

p OS1are assocured wrtt•.anr s»p ar tabacco by tpoustts) . 

and cla,ettt smolinj accounts for n+ost of the tobacco 

vu The ewnuted rt4t, .t rnk of pufmawh ad+noctr• 

t,nomi associated .smh trà,ttte tnnoLms by eto'uttr 

was 1•)i 1142•1 .N1 W+th tht poputtitron tontrois as 

comparrton and 1 .31 (0 }e .1 1 .t1 wnh she cobn carce+ 

tonnolsascomparM1On No~ettotUl,onbtlweMtpOUi4f' 

lobacco vst and bunf eancen oahe, than adrnocrcr 

rr,rru tsquamous tetl . M>+tI tei!, ierse cell, and other ; Fit 

. ~/I was observed . ' 

Sepa,att ana)nn .rtrt tonduc+ed cor wbtent .Mto 

prr .onallt rtspondtd and So+ whtm mtornyt,on a+ys 

obumed (som eurolate rnp"ents The tadds satrot tyr 

involuntary tapotute to ET5 were very oreni{ar fot droth 

groups of tespondtnts ; thtrefore, the eetuhs set noe 

presensed in the ubtts etparate)r by trp* ol neaondrru- 

Orne such tumpk 11 tht ty1,RUted tetalwt rnk of e++onary adenoca ctnorvs a+wcuted wrth erp*tnt 

vnol,na by tht spouu OR . 1 .18 and 11 .110 to+ eunoµte 

and reif•rtrponden7l, Ieropectn,tlY, tompar,na use+ eo 

eofon Canctr eoetirph . 

tffedts by ttsrdr tenttr wert at .o t .amrntd Yke 

odds rafros bY censer ranled froM a bw of 1 .17 to a hrit, 

of S i4 to, rnl of pulmonart adenocarunoma assoeetttK! ~ 

with tpc,usn'tiL arnu .mok,nl drreust of the kmntd ~ 

6ampk wn . nona of N .e rnd,vrd"l suudv eentet aqt .• ~ .+ 

N 

~ 

~ 

Jot 

~ 

~ 

0.114

tYa'4 QMNy.nN s, LH( cMC . tM M6 rlwY RfllWle r 

a . .c,.e M'Mi'tv^c rwu .ww'r, 

~ C«r 

i.~co. Bx~ 

u.rt evnh 

en • 3a0~ r^ • 3Sti 

r. 

INv.+tr .~ 

eo-l.n 

« • 7•0, 

A~ w ftr 

immi, c~ 

Alr.n, 

K /tt* M /1J31 )r et f i 

lanre.• 

M 1111 1t r100 , IN q1/ 

M w•bro 1i0 Q111 1 :! O)11 314 Kso 

Otir+r. 31t wJr it tl31, M etli 

•/n rrsn[an an Mt M qs )+ 1Jf W ft 2f1 Dt1i 

4. ..•M,w 

iyM ~Mrtt 2'°T M 01 111 AO u?W AO Dt 

,.,,,,,r us u.c . 2t et, 

Y fY.M1' 

2o Js 

3rr31~ 

iL+-41 

l n_" i 03, • 

11 r, r 11 O 11 aJ 

2) q-', 2J )~ X 

1) t1' .N /1 r1M)1~ w 

117 vs01 t0! LM1 2 .21 

i•t w 3, itt wa u1 

t+r+W%-A r+.m 

WtAt 2M A) ) , J A0 r1 s 10) 

46WI, V tto s~ ss ,41 107 

rs .a ..r 32 d s, 14 60 o, .J 

~ 42 cta0, t/ 1100, 11) 

O'+r 1t Q 1, J C 1, tu 

trw+~.w ..w ..~, .e b aDo, I C .t 2 

r w~.+ 

a.. r .k .~ .. 

asa o~c ~ n- t .c „~ s v 

edort.lJM1 a fiso, s~ o .4 tss 

l,30% .•,e0" •/ t„u 46 n)' . „o 

t7Ct)X•IrM1 f) r11 ., rt rt7 ., 13) 

S3f 00G-N M1 s7 d/•N 1140 l? 

sssooot H ni rn 3s 4100 sJ/ 

Wnwwr.~.u~+6 M tUJ~ M t111- M 

b ewv. 

IL~t+~~r+ 

Kh.d 133 1111, a+ Q) i, !•) 

C.rm 

cr .dwnr 

116016AIr .*` 

ud t3) 3, 

Ct ts .4~ 

33 C1~ 

23 61, 01 

H t3A, 

11r 

7d 

Je 

21 

'1 

tl! J, 2+a 

ett, ta, 

40, 1of 

LL), N 

slli 12 

Idtie+ HJ1NoN n+f..c• 

1t 

i. v .+ ..e . 

9JG OOC HoKoit+w 

20 O.G-1t Vfl PphAnrn 

t1C Oo: 040dW•n 

L .A .r1,t.A Aw ..nn 

na~ 

ts u 

n e, 

rtl3+ 

Ce)~ 

N3 .~ 

aN 1~ ~ 

11), 

r3 ., 

/i .)1 

it f, 

to~~ 

n1 ~~ 

n ., 

tS1 a~ 

/1o )) 

r1O .~ 

1120 

Ct .)I 

tJ+ 3, 

L`)J1 

tt_) 1i 

•f, 

ss~i 

fa aJ t, 7! 0241 11, t41~ 

11 nt 37 16 r1o ), •1 n)~ 

tt) Ct tl It (2) 1i HM itl 1t 

81 e/ u ac ru it M tlJ u 

Lta 046, sbl tl1 11 211 G31ai 

2• t, s•li 1 041 

1." 23 •s, /! 663) /6 n 3 t 

A'Wal ow Io 041 • 4111 tJ n1i 

c?t Ox ophrtM•n 3M 11131 it/ el M •3 • A i 

20 ooe ..1 e+,•c wwM+w, ss ssts •t ttf a/ ei/ 11391 

R s0 OC> M»,+ww 311 464 h 144 114 4, i01 O7a 

UNwsr. 2 1011 1 031 1 lf tl 

enates vsrt tutnrtca8r /if n,ftcant . •nd shey sAd no( V4• 

niLuntly d'iltr Gom orse anWhn . 

is+mam of rt4tivt risl •swcuted .r+th thr nvmber 

of cisa'ellet smoled by 4 spauu wefe /ynAtcantfy, tittroted 

only in 1he h,ghtu taposurt eltt{ory, 40 or mort 


c . ..« •w.W .4 .» a 0",..o," 

c~ renrtpddsr : 2 .06 (1 .N•) IFltand 141112i•2l11bt 

adenocerctnoml o/ sht hxti comp+rrn uses lo ir,bn 

cJncer tnd popu4lwn con/toll r»penNtly pdds ra+tos 

wert am,i+r, ahhou>ih aJ1)hllt iower . Io, atl (ypes ot kmS 

taae+ comb~ 1 .7011A7 •1,ta) Ind 1 .M /0 f0•2 .0b1 

Ofac1•yelrs .rrt tumrnrd at a ceNS+brntd t}wvwre 

Irf duratron and doa of eapo .ure to t1,t husb+n4 s csy• 

rrne t+noktnl The odds ralat la an cen types el prnj 

pncer comb,ned and (a •denocarco+ema o/ the iun) 

Ke drsp4ytd m iq 1, Separ+rt anatysh trert canduned 

wnh each conarot roup fa canp+nson . I+cauu Nx 

Fndtnjl wtse t,0 b+en+4 br •Kh jrp)p the Kyt/ks art 

ptesenttd (o, tht ttw contrd •efKS tombttsed fn . 

11)11 An ncrtas,nl rnl of tunl tlnce+ and aderwcarc,• 

ttoma of tht lun` nwculyd .rnh an rscrtasrr4 Mrr1 ot 

tepcsu+e to the tpouu's epl+reue Imoltna evas ksxad 

The posn,+a Irtnd n nsi by psrl•y .an o/ tVo"t a 

µttrst-clh, u{n,(K1n1 kr adtnoc .rcw+ortu of th+ du+tg tr 

t O Ot) / "elrr dou rrspome • tsbtierred w4~rn all 

Iuslopathotot cN typrs o! {vey carxer art eombmed 

pttnd ~ • 0 .071 . 

Eapd+vyt 1o fTS hom ranous wwcet tlunq aduh 

ik wts evafw+ed The resuhs ut wmrturaed sn Tab4 

• for t•rmpl,cnt of Drt+enul o+, the 4a11 m ttw table 

•ts0 tepresenl the t,nd,ngs usmg the t .0 control roups 

eomb"ned becauu the tndwtduai re+uhs usmS eK1, ton• 

erott aup .trt ent rely cor»atenl ERpossxrs so eoppetse 

ImolInI lrom syoustltl . olhtr hou+rhold men,ben, on 

!ht pb and ,n ather aclrvnel o+ aduh l,+t thocaarr ste 

trach assocuted wsh an over.ll 10-60ti% y qqrttcanl rk. . 

vatwn sn Ihe r»1 of adenoc .rc,nwru ol !hs h+rs2 /u 

ewted prr.~oustr ta tpavu•rt4led tipo+vret the eak 

p,I+Mlet to, all lun` ceMe't .hti0ut rfjArd lo cell t1-pe 

ltnd to bt ilthti, bwrr sh .n the tompirable t+tmutrr 

/a •denocarc«nonu of the hmt inntlKanl yasene 

utnds il c 0 05) sn rul oi adtnocarctrwtn+ bl tht 4md 

"re •ssocuted .rth rncreannq durlt,on tyearsi o( et• 

"urt to ctj.wte smole hom a Ipoure . Wher 1vw+r• 

hold members and wcul ocratrons fot aduh hovsrAold 

ttiposurts (IOR1 1 spouse and othrts Opsrrmates eN tssl 

tose hom b. .ett 10 h,1hesl r+ Ihe 30 a rnae .+t» ol 

t .posure cale•loh, hoWr .er, stends wtre not >,rnoaih {w 

taposuret m occuptt on+l Ind wcul unsrs#s 

No assocutan s.1t tound be+aeen rtsk ot an, tvpc 

of lun2 c+ncer and childhood taposute to tsjan .'aptt, e>i+'ettel 

. or all irpes of lobxco comblned lable 7 

p+esents the estirwttQ se4t,vt mks or lun` eaPrct, and 

adrnacarr,nonu o/ Ihe luna amons narnmoltey sbnsrn 

whose /11her, ossother, os orhtt househo3d Rsember 

/molItd duttna childhood None d,lleted •r{ndKamll 

kom un+rr• t'etn ottaposufe end amaurU snu>atd .*,e 

also tumined No i.I2n'tKam ek .Ittom tn txa wf"a 

four.d at anT krel of Imol,n4 br hovwhold +armbers 

"ft ch,ldhood . 

ditl'1RfiM 

One ®f tht mosl plslm ; Gndrkjt of ehis etuds a H+e 

`ntribulson of ahe hittopaholopcal eell erpts of krrs; 

tyncer an a pbDu4lan•batd lertes ot u3t•s a11 

Klttned lo dtletm,ne Wkt,mr vtoMmoler Otalus irv• 

Rntr-t,/ht % o{ )5f re--r .•td tLìble cates snlhn retoa 

.~ete c4lurKdas aarnocalc~nomat Th,s h}h p+opcvtasr 

ef adrnocacusomas and the p•rurny ot lo,,amcnn ind 

/ntatl eell cactnomat .at tBM,t1H,l arrens AA MWly 

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C om s t M p iNO4f.tMi 1110)bt) .1 

tyn N fl 1fD t N O) .•U?, 1i0 C 1+•111 

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4 

centen M the etudt 01 Kibet .nd Wyflder W, a timiL, 

propon,on l74'. .i o+ Krevberj It trpe turnoh wJs fov+sd 

in thea wrxl ol 9' non/rrtoi,ng rtrru/es who+e /eIi• 

reponed nonfmoLmg S71tus rts con6tmed by than r!• 

.+e». In the U^ted Sutet .denourcmom+ n the most 

tommon hntot>a+holo~ al Cen type o( Pt+mi-y iunt c•n• 

eer m women bu+ fhe proponion oi tll /envte iunj 

etncer uset wtth il; subrvpet o+ edenocerc,noRUS (pJp• 

illrn . tnru bronch o~ai~eorJ+, tnd ta4di n}a'w tSEFt 

Publtc U .er Ttpe 117i• tl17t 

Ouf l+ud, rn whicA tdenoctrc+nOrru n prttiannunt 

and rs tt,e cell sype ckut . awc4led r,u, wecreo .ed eMl 

A 

f 

r 

• t 

f 

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0 ~t 

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© 411 

It $ AINxd .iM u'*~ r te Lne trvrr rI i . .0.ftrc .rcs,rwr w 

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trom .duh ITS eajmurei n te+ comrtst ro rererai et! Me 

•tri,er ttudKy o( se,,.olunuh t :pau+e to ET5 Tnchw 

poubs et tl 12) m the mny/ ct/e•comrol etudy o+ hP4 

ttnce+ tnd passivt tmolmI .monA rarnn+olml won,tn 

tsctuded uses o( adenat+cmorru mclud,nl bronch+oiwl,eo(V, 

however, thtt ttudy K+ciuded r,o histop+thobf,ctl 

tevK . Thet rcponed tn Dddt (tt a hom 1 .1 to 

) A tewcu+ed +vtth the husbtnd / fub+ts Di6• 

ser tt Jl 1141 rtponed t)•told ekrtled nsd astoented 

Wlth the {pouSe I 1mG!

1W t ..st~~e+Irr+ ..e~ r .r .~ 4•t crrr rO .r .+ esp.+~n 

a cw+'a~. swe.r / .ary a+~nsnx .~w• 

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bolvwteN+N' 1 .1t1peM-13at i31n1d•)12r 

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111.311) S u qtT-1l1i tA0/0K•iDS, 

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iwHi .O)) 1per1tr0N 

cau, .a.-,0 ........ 

1•.• ns.•re' 

Owr, 

t). rt i)•t ?tf 

1t» 

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e .s tt osa W r 

tNnOS•2)e' 

142 4 V • : o•, 

>be 130Ce3•510, t3'De]•24), 

ore.w r .sia t«.W r .oto 

i.r .+ ess.u-r 

0, .•euuw6' t3lrt .l)•2o+r t{o 1 114• : t i r 

0 /00 tOc 

1 .1s t)+ar .ta, )2" an•te1, 

ta)o rotr,)t•),tr 2 6onii-)b, 

>IC tesr0u•JOOl tsos0 :a• . ."i 

t ..+,or .oaocti 

t . .•se•oac : 

' Nir+~.~t w' Mr utr siAr ~~ .~ frnr.w~ srrne IV N~cMis~+ 

'1lOM 

~1R v a~Awc.r tW.vt /M 7iY+ 

" i+c a' .arn r a w' .w ar t vw .+ « J .• wa .r s•h. .+s *r. 

w-r/h VhP tM+ KtA++w' Md irw*de wr'V .•r rrwM~ 

ttr.+.e 

'1t0At 

veaiL+ utcinoma, comprised 46 1% of the total knuk 

nons+ a} nc ustc 1n the Swed,sh ttudy o( ftrshaitn rt 

at 13i1. 57'ro of 77 ttmtie nonsma4en wtrt adenocu• 

cmomat and 31% tAu{mous .nd tnutt cetc urcrnorrwl . 

The only suoaticlfiy /tjnifKam TtS•atsocuted a.crtastd 

tisk was tot Iquamous and artull celi cetca+o++us, the tefl 

types with she hr=hts+ rotat„n risks assocrated wtth annt 

vnoklnj At the prtsent trmt +rnaif numbert Of /qwerasn 

ctn and t•nuil cN( c.rcnwm+s tn ow dau set prttiude 

an adtquett t+tstlsment of tisk aISacuted with [TS t>

41 Co4 Cran' Y tr ...ftiYq Mr++r. 

.rwLO-WOWt~ 

. . f .«rr.oV ...+^wy'rrw,~r .~/ ~r.,y~ .+! new.T r IMr c . wr . I~/~ r.~•~h s .rA .r~M 

M W ....N 

814W/ . 


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c.r* cr.rr 

tnr,M. 

hr..~ 

wr.e+ 

Ma tlrl q0 

WeM M do r 

pr,~ . ,.~ww ...+»r 177 eu 3v 

... ...~,.r.r.~ 

1 M.• iM w 4it) 

arrr.w so do h 

prAn lir,.a.r/ .r .rl .~ US tu tpt 

~ A{MrM W Kr IK 1 YA . r>ti1 IM•rr K'M" . arY rf•fiow 

• CAifti .M . Mwe r/rV 11 wr+ M Yw 

dur•tron In comb,rwt on may Y.tfd rrwn mtlanin{fuf d,i• 

ferences rn e+po+utt than Ihit meetured by duratbon 

alone The rncluuon of nules m the New York Nudr, 

with poss,biv bwer douy oi ETS t .posure from tmokrn{ 

wwts fo, (t+•e! ytjn and dunn{ a more recent aR+e 

peood mat h.ve reduced +he reUr+ve rrsk nt rrules tlut 

were not ;ender tpecdre A pudy /n nonheast Chw, 

whrch . 81 cornpirable in $12t to our study Ktuatly 

found • decreesed rnk o+ lun{ cancer usocuted wrth 

E15 etpotures rrom spouset +nd rt tuiSest, .e r,c+eatt•ed 

rrsk essocyted wdh pt+er+ul smokmE (40I Aj /,ug ;esred 

b, the authort, theye women had heivt eaposurts to 

both mdoor and outdoor poflutantt . Minrch met ha`•e 

obscured anv e(tect of ETS . 

Thr stud,es which ha,•t tun+r»rd rh,tdhood rapa 

eufes •,t more Irmned then those wh,ch !uw (ocusrd 

on tobacco use b~ /pou+el and thr over1,11 findrnts are 

inconclutrvt I), S, 11 .14, 22 411 5+ud,rs o/ 1he relyb,hty 

of recsN of ETS e :potures w{Eest thet reuU of a petenrs 

/mokrnE hu+orr n kss rel,ib4 thjn thit lot tpousts 1)1 

)9i and this rru~ account'T, p•rn (or Incomntencrts 

berween stud,tt Nnerrch n al f22i (ound e )•sofd In• 

crttsed rnl atwcurtd with =S a nwre Imoktr•wars 

durinl chJdhood rtnd adokscence but rw /ncrtau for 

chiIdhood e+powre+ ot ksl than 2S smoker•reaus IOR 

. 1 09I In most ttud,rs which have reponed posrtwe 

alsocNt ons, the fmdm{s hive bern prirturrfy for eyttr• 

rul E1S ecposu,ts m smol,ers rather th .n m rwntmoken 

Conei ti at, (Sf found a .qndrunt(y u+cre•r•td nik pf 

lunE unter IOR • 1•)i1 among /moken whotit Irlp(her 

emoked but no incree .ed rnk m nonsmok.en and elo 

ekvited r,sk assocuud with the u+her'/ t.mol,n` Wu el 

J!. ttti reporned a nontr`nd,ctntly ekveted msk o( ade 

nocircinor>•u of the lunj fOR a 11) in knules, W% of 

wham hid a history of smoking Srmit .rly• in a Swrdnh 

tuudy of (ern+lt 6un{ cancer whlch inc{udtd jecimln+oke du}ml .duh hfe erom a 

s•trtty Or tLpoSUtt •o6rrcet The a1t•oCYi,on wa1 i4e'cffK 

fo, kat1, adenocarcrnoma ot Mt krnll •nd /or atl (unj 

uncen comb•ned compared to colot, eancer 

Ac{no .{t1,ww*ti 

tw ...r,., .npww w•ecwnno- e•Mrr4sr .ww+• 

l.y .W w Mw w.. u,I, r/0 . PM ww Ar- lk,.r+w• wM e.rM 

..l+ «•- w .i . 1. .,,*. tM .u.y., Nm +A .ft Il.w' 1.-tu lias" 

1 . C•,,, y ., .., .u•J,ws 1.on.• .M b .y . i.•w w ra'4 `y+- 

Mt NyMt eqAW ia~rf! LeM'••va' A-..e / ..•( M . C.Mi+M 

Lw• G• .Ln eN .•v,. .y.a w rlt .airw, .r, D%I+t . I KHVr 

rr C .•r* a .w .t w r .,.,•y w . v.rn c•-v evw, e.r ••e 

e.a;02 FrnyIR GAU. faAw Nn1y tK) 

{[wna 1, klte ( w, Irefr.. E. . to Y . aM w .wuN w 

tav.. vr,Iry aN Lp r .ftr Umn, ? N)•N' . IM) 

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Mv.. 1wr1rK ir,ctr. .- t, C+er1 rN . la .er 1•' :••?e tfitl) 

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Cswcrte. .t Ke .tf( NI ) 

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2029051479


4

Garfinkel, L . Auerbach, 0 ., and Joubert, L ., "Involuntary Smoking 

and Lung Cancer : A Case-Control Study," Journal of the National 

Cancer Institute 75(3) : 463-469, 1985 . 

Another U .S . study, by Garfinkel and colleagues, is a 

case-control study of hospitalized women in New Jersey and Ohio, 

published in 1985 . It includes the following estimation of 

workplace exposure to ETS : 

The interviewer also asked about the average 

number of hours a day the woman had been 

exposed to the smoke of others at any time 

during the past five years, during the past 25 

years at home, while at work . . . 

The authors report the following : 

[The] OR for exposure at work during the last 

five years was 0 .88 [95% CI 0 .66-1 .18 ; 14 

cases, 52 controls] ; for the last 25 years, it 

was 0 .93 [95% CI 0 .73-1 .18 ; 34 cases, 118 

controls] . 

These two point estimates represent negative associations between 

reported ETS exposures in the workplace and lung cancer in 

nonsmokers . 


Involuntary Srnoking and Lung Cancer : A Case-Control Study' 

L.vnnncs Qarf)nktl,2 Oncar Auarbach,z and Lou Joub*rtz' 

1.OSTqACT-In a casa-control study in A hospitals from 1671 to 

ta8`, taf cases of lunp cancer snd 402 tusas ol colon-rrctum 

qncar (the Gontrolsi w+re /Csnfifwd tn nonamoktnp woman AII 

casns and controls w.rs confvrr> .d by htstoloqic ryrvhw of ftio", 

and nonsmokinp status and axpoaurss wars wrnfs.d by sntsrrs.w 

Odds nt os (OR) sncnasrd with Incr .as,np numb .r of ciparanrs 

smoltso by the husband parttcutarly for cipanttss smokso at 

horna 't•na OR for wom4n whose huabandt tmohsd 20 or mora 

oiparnnas tt home was 2 tl (45ti4 contid.nca hmm t 13 . 3 .95) A 

ioqtsttc nsqrasa,on anatysn anow.d a significant poa+Uw trsnd of 

tncraas+np risk with incr.asQd .xpoaura to the husbands srnokiny 

at hCme contr0l}10 for age hospital soQioeconomic claas and 

y.ar of oiaqnovs Comparison of women class1l,rc1 by numper of 

hours Utposed a day to smo>

, 

481 ()rrflnk .l, Auarbaoh, and Joub+ri 

verification of the smoking history ln a study of the 

histologic type of lung cancer in relation to asbestos 

exposure, 49 of 774 men and women with a discharge 

diagnosis of miaoscopically proved lung cancer were 

rccorded as nonsmokers in the hospital chart (10) . After 

review of hospital records, histologic sections, and 

interviews, only 10 nses retnatned who had died of 

primarv lung cancer and who had never smoked . One• 

half of the others had smoked at some time and, one•half 

the confirmed nonsmokers had a primary cancer other 

than that of the lung . 

lt is apparent, therefore, that more studies on involuntary 

smoking are needed, with parttcular attention 

giver, to obtaining microscopic proof of primary lung 

cancer and more detailed information about exposures to 

cigarette smoke, 

METHODS 

To have available enough subjects for a case-control 

study of involuntary smoking• we obtained access to the 

records of 4 hospitals-5 in New Jersey and I in Ohio . In 

each of these institutions, we identified all lung cancer 

cases in women recorded during 1971-81 . In 2 hospitals 

the cases were selected from the Tumor Registry ; in 1 

hospital, they were selected from the surgical index in the 

pathology department~, and in the other hospitals, records 

from the pathology laboratory were checked against the 

medical records diagnostic discharge index No case was 

selected that had been diagnosed prior to 1971, Cases with 

cancer of the colon-rectum served as controls Colonrectum 

cancers have been shown in epidemiologic studies 

not to be related to cigarette smoking Charts then were 

located and reviewed Cases that were diagnosed clinically 

only or by cytology, or as sarcoma or lymphoma of the 

lung, were excluded Those that occurred in smokers (or 

ex-smokers), according to hospital records, also were set 

aside . Only those charts in which the patient was 

specified as a nonsmoker, or in which the smoking habit 

was not recorded, were further investigated . 

All the slides for these cases and controls were pulled 

from the files (an average of -15 slides/case) and were 

reviewed blind (by O . A .) . In a small sample, slides for 

cases and controls were reviewed a second time to check 

consistency of the findings . Another sample of slides for 

smokers with lung cancer, and for subjects with diagnoses 

of sites other than lung or colon-rectum, also were 

selected for histologic review and were mixed in with 

the slides of nonsmokers . If slides were missing or not 

available, or of too poor quality for accurate diagnosis, 

the blocks for the case were located and new slides were 

prepared 

An interview based on a standard questionnaire was 

obtained for all cases and controls, along with microscopic 

proof . The interview was with the woman if she 

were still alive or with next of kin if she had died . 

Seven interviewers did all the questioning, three did 

interviewing in all 4 hospitals . About three-quarters 

of the interviews were with the patient or with spouu 

or children . All other informants had known the sub . 

JNCI VOL 75, NO S . SErTEMI

TABLE 1 .-Lui19 caM1ffl ill HTOflKti u•ho nn~r* nnokrd 

Recordr of 4 AotPUL• 197J-a1 

Status 

No of women examined 

At hoapials- 

A B C D 

Total % 

ldtcro.

4" Garilnk .l, Autrrbach, and Joub.rt 

Variable 

No, of easa 

No, of mntrols 

OR' 

}5t CL 

TAltl 5-STMOkr rrpoavse beJon tuwp cowcCr dio.pn.o.u . os elasriJud by hYaband'i smoking k&bvL 

N one' 

43 

148 

1 .00 

N one ' 

Husband's touW smoking habits 

Cisarettesiday Cigar and/ All typts 

Specification 

"$ f3arifnkel, Auerbach, and Joub .ri 

a1SCUSS(ON 

In a previous paper (4) the problem of classifying 

involuntar . smoking on the basis of the hus,band's 

smoking habit was discussed It was pointed out that 

questions directed at ascertaining a quantitative estimate 

of the number of hours a day that subjects were exposed 

might be a better measure than the total number of 

cigarettes that the husband smoked, inasmuch as not all 

of the husband's smoking was done at home . In the 

present study we classified the exposure both ways : by the 

number of hours per day the subjects were exposed to 

smoke of others and by the husband's smoking habits . 

We also recorded the respondent's estimate of how many 

cigarettes a day the husband smoked at homeIn this 

ìoup of women, husbands who smoked cigarettes 

smoked an average of 27 cigarettes a day, of which 11 .5 

cigarettes on average (M) were smoked at home . Of 

course, all cigarettes smoked at home were not necessarily 

smoked in a room where the sub)ect could have been 

exposed, In this study, the husband's smoking at home 

was related to the women's lung cancer, whereas number 

of hours of exposure a day to all sources of tobacco smoke 

was not related . 

A potential source of error was the hospital's report of 

whether the subject smoked or not, In this stud), 40% of 

the women with lung cancer, classified as nonsmokers (or 

smoking not stated) on the hospital record, were smokers 

at some time (table 1) . Another 13% did not have primary 

lung cancer It is apparent, therefore, that in any study of 

involuntary inhalatton and lung cancer, the smoking 

histories of the subjects have to be confirmed as well as 

the extent of their involuntary exposures Smoking 

histories of husbands were obtained for the 113 women 

who were smokers The distribution by smoking habit is 

shown in table 9 . As we might have expected, smokers are 

more likely to be married to smokers than are non• 

smokers The table shows that 43 of 134 women, or 32 1%, 

of the cases included as never smoked in this study had 

husbands who never smoked ; but only 21 of 113, or 18 6% . 

of women who smoked and were mistakenly classified as 

nonsmokers in the hospital record had husbands who did 

not smoke . Among the controls only 8 .5% of women who 

were called nonsmokers (or smoking was not stated) were 

smokers 

The table shows the effect on the OR, when one 

assumes that 8 .5% of the additiorul controls needed for 

the 1 :3 match had husbands with the same smoking 

distribution as the husbands of cases who were smokers, 

and that the balance had the same distribution as that of 

the 402 controls included in the study . The OR (or the 

husband's smoking increase to 1 .61 overall and are as 

high as 1 .63 for the 20-59 cigarette a day smokers and 2 .32 

for the women whose husbands smoked 40 or more 

cigarettes a day . For exposure to the husband's smoke at 

home, the OR are 1 .66 overall, 1 .53 for women whose 

husbands smoke 10-19 cigarettes a day, and 2 .85 for those 

whose husbands smoke 20 or more a dny at home Thus 

the inclusion of women whose smoking habits have not 

been reviewed greatly increases the OR . 

TABLE 9 .-Nypot)ttical OR resvltinp from rombininp wrom .tn in etudy u•itA women oripinally ctassiJud 

oy Kotttmoktrs but u•ho actaally smoked 

Husband's toul smoking hsbiu 

Variable Ciàrettes; day Cigar All Touls 

None 

endr or 

types of 

< 20 20 39 Z40 

pipe 

smoking 

No of cues 

Nonsmokers (in study) 43 11 82 30 18 91 134 

Smokers (originally called nonsmokers) 21 9 43 24 16 92 113 

Total (untcreened) 64 20 75 64 84 163 247 

No . of controls 

Nonsmokers (in study) 148 45 102 52 55 254 402 

Additional controls' 119 88 90 45 47 220 339 

Total (unureened) 167 63 192 97 102 474 741 

OR 1 .00 1 .01 1 .63 2 .32 1 .39 1 .61 

None 

Htuband's smoking habits at home 

Civarettu/day Cir .r All Totals 

l 

The classifiation used in this study might be criticized 

because some women married to ex•smokers could be 

counted in the same exposure ategory as a woman 

exposed to smoke up to the time of he~ftnal illness . 

However, all patients who have gone through diagnosis 

and rcreatment for lung cancer had some period of time 

when they were not exposed to others' smoke, either 

before or after treatment . We believe that the classification 

we used was indicative of the "usual amount of 

smobce to which the person was exposed ." To determine 

the i:xperience of a"pure" nonexpoud group, 17 cases 

and 56 controls in this study were identified who were not 

expcned to the smoke of others during the last 5 years, 

during the last 25 years, whose husbands never smoked at 

home or elsewhere, and who never were exposed to smoke 

in Kheir ehildhood . These cases and controls were 

eompared with all other subjects The OR was 1 14 (CL : 

0 .81 . 1 .59) . 

In conclusion, we found an elevated risk of lung 

cancer, ranging from 13 to 91%, in women exposed to the 

smoke of others, although the increase was not statis• 

ticall% significant . The women who were married to 

smokers of 40 or more cigarettes a dav or who were 

exposed to the smoke of at least 20 cigarettes a day at 

horne showed a risk twice as high as that of women not 

exposed at all . This result is consistent with the dose• 

response risk of exposure to the husband's smoke shown 

in some case-control studies (2, 3). A dose-response 

reLationship was confirmed in a logistic regression 

analvsEs . The lack of a relationship when exposure was 

classified b% hours exposed to smoke of others map hale 

occurred because this variable does not accurately mea• 

sure intensity of exposure . There is no consistently 


Inrolunt4ry lrrnoklnq and Lu" Cancor A4g 

higher risk for certain age groups or by histologic types, 

or by exposure at home or at work Exposure in other 

areas carried a higher OR, but this finding is difficult to 

interpret 

!lEFEiiENCEB 

(1) HIRAYA4A T . Non•unokmg wives of haw smokers havc a high 

mk ot lung c .tuer A suudy from Japan !t Med J 1981 . 

!>32 1 e s-185 

(?) TR>anroE•t.0s D . KAUN-nstr A . SrAaRns LL ct al . Lung cancer 

and pasttve smoking int J Cancer 1961 . 21 :1-4 

(1) CoRREA P . FoN7HAw E . rIOCEl CW, in ut Passive unoktnR and 

lung anar Lancer 1963, 2:59i-597 

(I) GARrtwuL L. Time urmdi in IunS cancer morutity among 

nonsmokers and a nou on pautve amoktn` JNCI 1981, 66 

1061-1066 

(S) DLAIAT GG. WYNDtR EL Lung eaneer in nonunoken . Cancer 

1964, 5! 1214-1221 

t4i SANoLta DP .EvtRsoN R6 wtuox AJ Pasuvestrsokrn6rnadult• 

hood and ancer nsk Am J Eptdemtol 196$ 121 .37-48 

(7) CH1r. WC, Fvr.c SC . Lung cancer in nonsmokers in Hong Kong 

ln Grundmann E, ed t,.ancer campaign Vol 6 Cancer 

eptdemtologN Stuttsart and tier, York Flscher VerlaE . 1982 

199-202 

tdl Koo LC . Ho JH .C . SAV, D Active and passive smoking among 

Irmale lung nncer patients and controls in Hong Kong J Exp 

Clin Cancer Res 19A3 4 .l6i-375 . 

(91 FRIED40, GD PrTTtTI D9 6w,ot RD PretalenceRndcarTelatei 

of passive smoJ

Janerich, D ., Thompson, W .D . Varela, L .R ., Greenwald, P ., Chorost, 

S ., Tucci, C ., Zaman, M .B ., Melamed, M .R ., Kiely, M ., and 

McKneally, M .F ., "Lung Cancer and Exposure to Tobacco Smoke in the 

Household," The New England Journal of Medicine 323 : 632-636, 

1990 . 

Conclusions based on a case-control study of 191 men and 

women in New York State were reported in 1990 by Janerich and 

colleagues, who wrote : 


Exposure in the workplace was measured by 

recording the number of smokers who worked 

with each study subject during his or her 

lifetime and the amount of time the subjects 

spent working with these smokers . These 

exposures were compared for case patients and 

control subjects . Estimating the odds ratio 

as a continuous variable for an equivalent 

differential of 150 person-years of exposure 

gave an odds ratio of 0 .91 (95 percent 

confidence interval, 0 .80 to 1 .04), indicating 

no evidence of adverse effect of environmental 

tobacco smoke in the workplace . [emphasis 

added]

t 

f 


.J : 'k---THE \Etl E\GLk.\y fOIQ•v,U, of mCDICt\E 

LUNG CANCER AND EX.tOSUitE TO 7•OSACCO SMOiCE iN THE HOL'SEHOLD 

D~,toxT T J, .t>P 

prnalttnq an0 tuhq canC .r es ot qrtat pupt,C Matth rmM• 

tdnoa rS4mi pffvtous ttutl,ts hava Wq ;tttro that txpP . 

aur• to MvtrOnmfnta1 tLCaCco lmptti m!rN AouNnOtO 

can uus4 tunq cancst• W ottWn Mva tarnd no anatt . 

Snw+, .inQ by mi spousa has bftn Pha m0i1 COAtMOnty 

us .c measurt of t'h,s atposur• 

blrrfzoas In ord .r to W ttrm,na wharhar k,nq ca•+cyr y 

anicciata•6 w,tr axposura to tobacca smo+c• wrCvn ma 

MuselroiC wt conaucu-C a paputaton•basea use•••con . 

trot Sludy of 1qt pat,tnti witn hiitOtOQ Ca y Wn1i Ky pn• 

ma'y tunQ canct, w*a haC rNvt• amoksC dn0 an ~ua 

numthlr Ot ptrsOni wtth0ut fung CanCar wtto ha .'. M1fvpt 

trnokoCS Ltatima rts,0tnlia ; hiftonaS tnGIutltrg M1tOtTn&• 

tWn on ttp63utt to tnvironmtntal tobacco 1mOtcf wart 

OOrnp1llC and ana yYtC ExpOtWp waa fiRasurlO,n Itrma 

ot'sToka'•yaa't catt'r+,ina•C by muqtp+y,nq tht numbar 

of ysars fn aach rall0anca by 1fH numbar Ot trnpk!•'Y dn 

" hous .haa 

T HE 1972 Surseon General's report dealt with the 

health consequrnces of passtte smoktns or en~i• 

ronmental tobacco smolte for the fint ttme ` In 1986 

the entire report was de%oted to the usuc : it concluded 

that ••rn\olunlar\ smoktnS is a cause of disease tnciud• 

ing lun>S cancer tn healthti non•smolers "= llore than 

a dozen tptdemtoloStc stud,es ha .e a3srssed the rela• 

tion bet"ten patsa~t smoicani and lun ; cancer }'r The 

(indine ha~e ran5ed from no detectable increase in 

nsk'"' to a moderate (about twofofd), stattstiealir tis• 

nificant incrcue "Most studies ha~c found onlv 

small ele~ations in risk, which art frequently not >.hu atrs ctrmCil*we 13 ea 

trrt .rsth approxtrnact}, 125 4uSnwuc tar ttrsnR+ent fac,t,lm an 

ppu4uan Yaar sf ntarf~ 10 mtllwn pevplr , tprttai rtlrm fa 

rap .d autrtunmrnt k tasrt o( tunt cbnctr rac n+ablahM! ln th 

115 tactluln to lha, panrnu cavl@ ar .denliRrd and ennikd u a, 

afirt d,aq++osrt u pats,btt ilt we- taat+ ef 1mnK canrn ,i .atrno 

etMfcail,, k;utolorcaJt., of bothl trt rtrulaN, drn,rfifd a, 

pnx,t.ann; hoep,uL 't'ht %*t• . 9'ark State Can :r Yi.t;uln 

thtekrd rtwtanti• ta .drnuh an- r~ ,Aa, .eyh, aa~t bt•rt a4i 

1e+ I~t~+t~ ~lwt~p,ui•Kaard lte~Ywrtl>K t .arm 

l~1lV,il4ttan tn tin~i,t4 MaJ7 lNL{ltltv ab1a111rfJ frs~ n1t'!tY 

mrdfesi rre .rdt A1i tht tatr Ptcxau npntd u MaweS w, 

tn,owrd .r u k.mrr smckan of .k,aw fn+atMt t+urr, eu 

tAc.w KK ttmtattk ia . utr.phau and thrrr smsiny tutw 

tanarYned Te Ya Mdudcd u a'tare' M tlu atwt ., a pnrnt R. 

rts,It IA 11N TJi'BUnf,, ans k 4tt•rrn 2@ an6 /0 .esn rf 

Wvtr lu .t tmoktd R+ort t}un tt70 tysrtltn lnansnwlrht of t 

1TOl,rif at tWnt UR1t aul nat lU~t tlf+6ard t>sart than 100 c1rtP 

i . tl.t It) +tsn Yn•fort /urart t6a .+nrr an+skrni W ka .t i 

~ n+ . tiufi,au .t pnrnan iuty tYetn Irtwern Juh 1 1!i? 

Ckcrrnber 111, 11i+ . ttul .at etMfirmt! sr, rresaft .•tt .an et 

'athoi,ficiJ stecuntns anal chnltal rtcarda Stfde+ w NaW o, 

wt .rrr a+i"tat>'k Sof all kat S,'t at tAt tast'atKnn U7 rnatt 

an rtnt•. .ed 4. MrtsnSston he .as fttndrd vrcF rrapa•ct I 

~suert's rueul dla~no+u anokuq l»loe~ aM atMrr rttl iaf 

laumw .+ t .erc c+Rductad .ttA 16 ;wrrcent ®( +ht rt.g~btt p.t~ 

at tAcu ttoet+t avutaak retauvek s+ hunAt twrrqtt"t 

Conti'9t aYIt)tSu trt tadlvdual1r r+auhed t0 ls4 tsurriu 

tie+v stirctrd !r scrstnlry ttx >Tiln t( thr wr. Yrri Stttt dk 

sitxt .f t,{ata Vrlucln T'4r trrrrt .f can+rolr .u t4rs), 

apptt+¢tult kact It ru p»putaust.ba .ed anA prro .Nhd aws+t, c 

rsarnuuon atcruar. to perforra t!t anatch,nS A bi af po, 

tor,trct tut.pecu fw tatR uat paurnl .at wLrctrd .n t!w iss 

a ;r (adun f vt vt+nt, trs . and twMr. .! m,drncr Pstrnlu 

trot eub)rtu wtts trntantd b+ ukpl,ofu TTt finl el+t+tatt n 

rho as Sound to nutth tAt sast Hl+znl tn trrmi st nnoa nt 

ty tttionstnsirr st Sormcr tn+alrr t and aw aS+red ts Wlnps 

enrollyd u tht stud~ An add,lwnal ~sctch,n~ ~ansbk carudr 

thr umt .( dlta COLKUas aao tht nqr .I u+ttnw . - t t ._ 

ifttcrv,c~ rMti, st,t pawnt .f caAwt tuh)ect .tnut r+lmuv 

wrrnisu respaMent WAtn a surr .,Ktu caa< ptiunl 1,ad 

i.urrvx ...r/, .t a.too u+unuor! s wrtnSsu tar As w k.t1 m~ 

~iqV 

~rl 

J"A 

~ 

~ 

I

t 

%ol ;:1 •o lo LL''%G Ca .NCEi< kVD HOLSEHOLD TO1+CC0 SMOKE - JkNE0.ICH ET kL i1J 

I control r%~n .ehen the control tublect .aa avatl.bk arrd rnUtry to 

be tnttn/t-td Furthrt tn(ormatwn M the entt6ait tued tn tit 

uud, u atat4bit rlae .hert 't 

Data -ere collrctrd (or 459 c .ae-tonlrol P.atn CN thste . 242 lun 

utre lonntr tmokrn and 191 paun had ne-tt swwhed Btparaunt 


the rettdual ttfecu of d-rtct a+noktnt froen thae t! µur .t em.ttnt 

smone iormer amokrrn bn .oi+ey more compln anal.ttc and wtter, 

prrtstronal uturt thsn does an rsamtnaasler n( ust t{fecu a'! àaa,r .t 

tmok-ne m thox -ho hatt ne+er tmoked This report a tl+nr{nrt 

itmtttd to perwnt -ho ntt tr tmoked Su al the 19 % ptn .ho had 

nr'er tmoked -tre mumatchtd tn trlm .t sf tht w*t .( ntervr+ 

~dtr/rt ts wnotate and ha .t thr•rriorr Oetn ntluded Tltya, the 

anal .ut rrpotted htn -ere 4std twt I91 taatche•d caae-contrel 

pain k Ltal a 1 :9 pain .trt rwtmsir.red titretltt . twd auetnatte 

atrl /AIttYK.td ttJr B : 

411 mlorminon .at collecuel dunnt a tan•ewfacr xttrn .e- w+th 

ute oi a®rtcoded que+twnnarrt Cau'autnu and tanlrtl iuyKU 

•ert rntente-ed tn t%actl• the tant . luluon and nct)tt iol uetw 

concern,nS the clinical aapecu ta( thr currtnt eiAedrtaw condtuon, 

both troupt ant-rred the tame qur+t .ont 

InformaHon about tmoktnS m the houuho7d .u eollened .rpa• 

ratrl, ior tach re•midence rn rhieh the tubjrci had Irvrd for one .•etr 

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 

aart the aub)tct li .ed in tach rn dtnce bs the numrrr s{ smokm 

lrnciudint tht epousei tn tha{ rntdenct TAt }loducu fol aA retr• 

dentef ~trr tummed 

SmWtnt b, the spouse .ta a1w reeoltftd .epanrel* frvm that In 

otfier houtchold membert rn a aub .equrnt aectton t>t the quntwn• 

nsut The tnformation conture•d o! the number o( tan the tpeuse 

had smoked .htle httnR with the t"e paneni or eontrol tubltet and 

the number o( ntarettes tmoktd oer dat Smoktr•vtan of tapeurt 

6om the spouse a tmokrnt wttt eakulated m the aame manner u 

fm the entire houuhold Psck••ean sf eapaure (rom the tpou .e 

.ere calculaied b+ mulupl .tnt the eumbr. al packs emoked ~er dar 

b• the number or .ran that thc apouse emoied .rh,le Irv .nt .rth the 

tublrci If the fublect had besn mamrd to mon than one tmoirr, 

thtn Ihc numben o( tmoker• .tan and pack• .ean a( ea"ure kr 

all spouses wtrt tummtd 

The qutattonnatrt also tneluJed utt .au t+n npewurt tn t•nnron• 

menul lobacro amoke tn she workplaee and uM ooauJ setunp wl• 

a+dr Ihe home The Ioraut (or the+e aluetlweu tlldered Gom that 

axd to cs(ltcr data on espro.un ut the househoJd 'ftie sumeaan 

results of thu anal,tu are Preunrad Aert, dewled [ .dusr an 

stulable elsewhert 't 

Staiutteal tKhntqun appaoptutt be the anaJyua d tt.d nduallr 

matchtd cue-control ttTn .tn ated se For tlutn t .( plesewu• 

tuon, percenutn wtn ubuLted !or ux pauenu and tsntrol eub• 

)tcts trpsntel+ rather then for ttute6 .d pun Hc erer• tddt rs• 

uot wert eomputed ae+ the l .aut .f tl+e .+.tthed pun The 

conditionaJ IoTauc•ttfreaaron .wdd .u u.ed ta tht ntJuvwte 

aNlvsts " ComparuoN o( tJtt el .ets ttf uroaurs that Kcurr.d 

dur .nt dt(frrtnt penodi of tlt aul?eeu' 6'rvu rtn "u'd .n t+ralut• 

tan e( diRertncs ia the tnt{rutudt sC appropnau fatuuc•rttrrt• 

aron eoeRtnenu Feu tuusueaJ traaj .l tkest Iiffcrc.cet we 

used the v.runer-evvatianu nuuu Loe>, ele bRstuc•rsrtursn 

ar+ah.ea 

Xxx"T$ 

Smoking by spouses eontributed a Large propor• 

tion of lifetime e:posure to environmenul tobacco 

smoke but was not the chief source of expoaure . Tablc 

I showt the amount of expoture to env'uonmeniml 

tobacco smoke (expressed in amoker•yean) dunng 

childhood and adolescence, during adulthood, and 

from the spouse for the 191 control subjecu who had 

never smoled, There were only amall dilTcrencey be• 

twctn men and women . The spoux contributed about 

30 percent of the lifeJme amoler•yean of exposure ; 

the correlation eoefficienu for expo .ure from the 

spouse and lifetime exposure were 0 .37 for men and 

T .ot. t Oub9otmx+ d+ fv+Or•Y .en a E,tttcwurs 90 Enwrmn ., 

tNyrLl Tpp6eioo w+ tN Mpstai+'0'Z a 

C,naat w tyt+u+t 

Lqam teenar•}rr*, 

eatan tSD 

Y asll 7 

$2 1242 1 

sa+u' - r'++r+ 6'nAi ca,'Mil°w atl aittaowts' 

+Mweso tsa[X7a K 1916 2 

Mtrr M bltMa ttAaet 7) 1 )0 4 

Ct/nuw . vt>'o dtttewt tait.n S 91 9 tt 

sr . 

a,. .• 

fw+an'raww ktw etewre 

t+ltao aiD 1)es110 N1s/1t 

M/crw er 4{"nu tarywwt 2J 0 IO ' 

Cesnuot• ase t.tni.r tyaesit 9)1 a rt 

rwAilr'rt4S t•f1a4 aeUMr !M M~ MPt tkM tp~ 

aau., sSD It Isll 0 M 1t :11 

ratr. tt W .a est. .re x 1 s4 t 

Cavnls.r l.0 kH.1to tyeart a N 01) 

•a .r . e t - t9 r• . .sat a .* nw tL 

.qr.r W ..,r. r etta.w r+ ft r. .• . b e7 a . . aa rd 

t..w er . r .r. iwa~ s, .n ~v~. t. .,rss•+t w .rr. r wtw ue 

•t.aww.l, ~.arMai 

0 .$1 for women Exposure dunns childhood and aclolescence 

(

f 

634 

Taar 2 n«aW ot 5"Okr rw's oi EAao* .rn o E'M*orr,.r,w 

tooaaz SM+o.e to e++ t4ak o+ t-ur+q Cancw ar+onq r .'sa,a wr,o 

rr.,- .f SMMr•a tao•e rrW t0o Cpannn • 

~ 

t . .raaa tfi,a LM .n C.-r+... hrt.qrMadl 

cti~ rw .. ..~«,k . 

0 71 .1411 61J7 6i 

t- :e {~ lJ 1 M 0t I) 

.rd fi ~i~ a T it! Ii 

t . V rT Itt U 

3.iloer 

AI 115 t+ 

M ile ti 10 34 3 

!0- e 

.'e 

L1ronr 

3r,1tii 

:t li .ri 

SI0le, 

. s i ns 1 

0 3I ~tf /~ 33 ct' 3~ 

- :+ :o~to31 I~'e u 

]3-J. SS~u3 ..,ten 

x1 . u I u 01 ao '20 ., 

33 tt+ 31 It iu 01 

• IM :j 114 u : . 11, 6, 

S}{B VEw [VGLA .vp)Ol-'R.VAL Oi HE.DtCNL irpi t ifX 

t e*,O 66-1T31 

3010 tf.-3Mi 

0 rr i0 1.-t tt~ 

anro 

1 110co 17-1 e3t 

t ti i6 3t-I `•6I 

•s ..» . t~ ~ - ,.n a,.. .. iw...~ chf.,.. « 

w. . io . r.w .w r ... . ..• -..r . .... .r. .*e As 

•e ~..~. ..~ a..- « ft•..µ .... ... d. .. a . .n .. Ne 

sr I i fon .i AP 


durins adulthood were eitimated to have nnualJv no 

efTect on nik (95 percent eonfidence interval . -3 .3 to 

2 B percent) The difierence in xhe maMrude of the 

eR'cct bteween exposure dunns childhood and adotescence 

and exposure dunnS adulthood did not achirve 

Ltatutical st5ruficance (P w 0 12) . On the buu af 

the distributton of exposure le-,eb dunn` cluldhood 

and adolescence among the control subjecu and the 

masrtitude of the effect of eauly expoture, we otimste 

t~t approximauly 17 percent or all lung earurrs 

t norumokcn can be attributed to totpcsure to paasive 

smoke i.n the household duriq ehi.idhood aM 

adole+cence . On the baau of the oddi ratia{ for 

the 129 case-•control pain wbo were iatervicwed directly, 

approximately 19 percent of lung eaneer 

in norumoken appean to be atuibuuble to expaurt 

to environmeatal ci{uene amoke in childhood aad 

adolncencx . 

Since srnokin= by the rpouae hu bren the tsWrt 

commonly reponed mcaattn oC cxpo{urt to environ• 

menta! tobacco atuoke ic prtvious studies, we eresmined 

expauze hom tbe spouse txpantely, att}sougb 

exposure to et+virontsuntal tobaecv acsoke from the 

rpouse is also included in the tesuJu shown in Table 2 . 

The odde ratioe for exposure frequeatly d;iffercd ac• 

cording to the rype o( intervieti ., etpeelally for the 

dats on exposure to a apouae's smoking Table 3 xbtrrfore 

shows the reytilu of the ansJysn of exposure 

to environmentaJ tobaceo smoke from t3te t;pouse 

aeparatciy for subjecu irtterviewrd directly aad tborc 

for whom sutrotata were irttt:rvie.wtd . T'be odds ratio 

for the dcvelopment of Ittn{ cancer for t6cxe who 

ever had a{pouu who smoked, as eomparrd with 

those who did eot, was 0 .93 (95 percent mnl,dcnee 

interval, 0 .55 to 1 .57) for tAo.e interviewed din•ctly . t• 

tct•r:u of amoker•yan or tapoattre to the {pouse'a 

smoke . the raulu abow little ef!'ert, with an odds ratuo 

of 1 07 for 25 or more amoker-vean of exposure t95 ` 

percent confidtnce intenal . 0 .59 to 1 .97) . Lumatet ~ 

based oe pack-yean of cxpoaure from the spouse were 

{,rrtitar to those bued on amoker•yean For botA 

meuuret, there was little evidence of a trend accord• 

usf ta amount of exposure among those who were 

expoeed . 

All analvsn were repeated for onlv the ust•-control 

pa3» for whom we had complete and internsllv coniutent 

data for all mtdenca and mamsèi Anv patr 

wai dropped from these analyses if data wtre tncom• 

plete or musinj for either the t:ut patient or the control 

subject, kavtns 113 paiR of nonsmoker•t Our 

purpose wu to eniure that our eonclus3ons were not 

dependent on the particular methods we adopted to 

handle utcoWi{tenctet or misstn ; uerru in the dau set 

The findingi were stmJar to those for the entire group 

of 191 pun Tht odds r:do for exposure to 25 or more 

tmoker•yean in childhood and adolescence .+u 2 .59 

(95 prcruet eonfidence utttrvsl . 1 .22 to 149) 

Laposure in the workplace was measured bv recordin` 

the number of smoEen who worked with each 

study subject dunng hy or her lifeume and the 

amount of time the subjecu spent working with 

thex {makets . These eaposurn wrre compared for 

uae patirnu and t*ntsol subjecu E.rumannt the 

odds ntio aa a continuow vanabte for an eqwvale»t 

differenaal of 150 perwn-ytan of exposure save 

an odds ratio of 0 .91 (95 percent eonfidence tntnval, 

0 80 to 1 .09), indicatin` no evidence of an advene 

effect of envtronmenul tobacco amoke in the work• 

place, Our aaaeument of smoking in soctal setaap 

used an un(ntrd, aemiquanatauve u+dea ut wlueb 

the cau patient or control subject used a{eore of 

0 throu`h 12 to indiute hu or her retui .u expc .ure 

to tobacco smoke in social settinp dunn` each decade 

or tife . Cumulative iifeume rtponed awra tunFed 

from nearly 0 to rrwrt than 70 . The odds noo for an 

increuc of 20 in the t:umulative aeart wai 0 .59 

(95 percent a,nlidence interval, 0 .F3 to 0 .11) . Our 

analysis of atpo.un in tadal setrin,p vnt,d nse of 

ti,is inda sbowetd a{uriatiealJy {isntficant invrne utweiatioa 

ber .m tavironmenut tobacco atrt,oke usd 

Iu3y Causer, 

I)sacu1.91094 

We iound a suuitiutly sienificant adwert+e es'ea 

.m reLdvely high kvelzt o( esporurt to enruvnrtmataJ trobaceo 

saiole dutin ; the eariY decadn of life (up t9q t,lwe 

aV of 21) . For ebo.c wbo wcre e:poed ta 25 oe tseat 

amokcr-yeua du.riag tbeir 6rst t.w dendea of tik, tbe 

rial of tuni nacer doubled, Tdia tim*unt of aporure 

i{ equiwltrit to tiviag witb, tt0ort thaa ow tuno&erN 

tb.roullbout chiidbood and adai*=ct - a lil* bsttC 

troc uaooauaoe icvd of erpwurc. Aa expxur~ 

this level was rcporud foc apprc:zieuately IS psreeat 

the enettrol group 15y eootraat, we found no a,~ 

e!!ta or ctpaure to eaviroamemtal tobarxe t+ 

dutin{ aduJtbood, indudin{ e:pown m a aporr. +viC,P1 

).A 

NOLA 

CID 

N

~ ol )2! \o 10 LL'NG C .~'sCER t`D HOLSLHOLD TOMCCO S .~tOKL --J{ .\LRICH ET kL .1J : 

T`Dis 3 t+4auor+ e Soousa s S+rok,N to trv oknt or Lwq Cancs, 

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f .wr/. .n• . . 

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Ci a- RL._ ..« . Or. 

rywi. . 1 r. . w rrr 


smoked, Although problems of recall and other poten• 

tial biues may have influenced the raults, our data 

suggest that exposure in earlv life may be a limited but 

important contributor to the nsk of lung cancer in 

nonsmoken A previous studN wit}t a smal' number of 

subjects found little evidence of an elevated nsk 

of lung c.ancer among nonsmokers whose parenu had 

smoked " Children of parenu who smoke ha%e been 

shoMn to be apeciall% suscepuble to respiratory prob• 

lems that occur soon after exposure to environmentaJ 

tobacco smoke,s This type of suscepubifiry might 

initiate changes that eventually lead to lung cancer 

when the exposed children become adulu, but we 

know of no specific mechanism that would explain our 

findings 

We found no adverse e(iecu of exposure to tobacco 

smoke in the workplace, althou`h we did not have 

enough information about the bevel of expo.ure in 

the workplace to auese the precision of our meaiure• 

menu . The apparent protective s:fiect of exposure 

in sociai aetunp is difficult to explain . During the 

course of this study, s,etulations in New York began 

to restrict smoking in the workplace and in social set• 

tin`s such as rcstauranu . We did not anticipau thiu 

development and cannot estimate how much the 

awareness of these new ratrictions might have af• 

fected the responses of the study subjects or their 

surrogates . 

Evidence is clearly mounting that tobacco smok .t 

inhaled pusively by tsonsmoken is potentially cur• 

cinogenic . In a recent study, Madure et al r' found 

elcvated levels of cardnojens in the blood of pusive 

smokers Levels of hemoglobin adducu of 4-aminobi• 

phenyl and adducu of 3-aminobiphenyl were sig-nifi• 

cantly elevated in subjecu with confirmed exposurc . 

The validiry of this findinj was supponed by addi• 

uonal evidence that showed a tharp declir.t in thr 

kvels of adducu among smokers who quit' 

At prnent, information on put exposure to ent, 

ronmental tobacco smoke can be obtatned onh b• 

interview . The available biologic marken, such as co 

tinine, cannot be used so confirm exposure that ox 

curred years or decades earlier . The use o( tntetvse• : 

to obtain a lifeume history of exposure to puu

1 

J 

836 THE 4EW ENGL,IND JOU0 .NA1 Or 1lLDICINE Lrpi G . 111110 

of exposure also failed to exclude the null valut" 

Garfinkcl et al„' using a difierent mcuure for durauon 

of exposure (husband's smoking in the lut S and 

25 years), found one si`nifiunt usoctstion among 

the large number examined Exposure due to smoking 

b% the spouse . cxpressed in tcrms of pack•yeat : 

while the spouse Aas li%~ing with the subject, wu 

Wund not to be sifnificantly associared with lunj can• 

ttr . Using a comparable measure of exposure, Trichopoulot 

et aJ 1 reported relattvelr large increuei in 

riuk (treater than twofold) 1'erhaps our data do ssot 

ahow that smoking b~ the spouse increased the tisk b .r 

itsclf beuuse smoking by the spouse made up only 

about one third of the subjecu' Iifetimc exposure 

to cnvironmentaJ tobacco smoke It is aiso possibie 

that phvncal circumstances and dtfTerences in studv 

areu . the size of retJdences, vcntilation . and other 

importan ; phveical aipecu of the ltvtng condition>,, u 

well as social habits that alTect exposure within the 

familv, will need to be measured and Inahied before 

tbe diAerences in findings among the studies can be 

eeconciJed 

The evidence we ttpon lends further support to the 

obsenation that passive smokunj ma% snerease the 

risk of subsequent lung t :ancer, and it sutèsu that it 

vta• be parTtcularh important to protect ehildren and 

adolncents Gom thu environmentaJ hazard . 

'Ae art tndebted to Mdrtas Vuei .ou tot hu usuunte -th the 

t:ompuur 2rraSTarnnunt uaed tn .ur anaJ»n 

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s N M.u .e rs>tiy 1 P4tJ t:ar.. W 1991 . Y t0i t• 


Ma .fsaehusctu MedtcsJ Soorty 

Irgistrv on Conunuinl Medical Edueatioa 

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aa IW .Il..)i7 .7i 

To obtain iLtformation on continuing medical education avurxs ia tht Wev Entland arem, 

ea11 berween 9 :00 am and 12 :00 ooon, Monda7 through Friday, (6171 /93•4610 or sa 

Muuchuscru a•i00422•2303 . tKt 1N2 . lf writin{, direct eertespondenee so f4o"m 

ltejurar, Musschusetu Medical Soeiety, 1110 Main St ., K'alsham, MA 02154-IH9 . The 

booklct r free to MMS memben . IS 00 for aonmembert


5

Kabat, G .C ., and Wynder, E .L ., "Lung Cancer in Nonsmokers," Cancer 

53(5) : 1214-1221, 1984 . 

In 1984, Kabat and Wynder published results of a case- 

control study of hospitalized individuals, mostly from New York 

City . A total of 25 male cases and 53 female cases and their - 

matched controls were included . The authors wrote : 

The plausibility of a role of passive 

inhalation in lung cancer can be questioned on 

several grounds . . . 

Cases do not differ from controls except for 

the greater exposure to cigarette smoke at 

work reported by male cases compared to male 

controls . 

The authors reported that 18 of 25 male cases versus 11 

of 25 controls reported being exposed to ETS in the workplace . 

This result was statistically significant at P = 0 .05 . The point 

estimate for workplace exposure of males was reported elsewhere as 

3 .27 (95o CI 1 .01-10 .6) . However, the authors' reported results 

for women are inconsistent with their conclusions on men ; 26 of 53 

female cases versus 31 of 53 controls (i .e ., fewer cases than 

controls) reported exposure in the workplace . This result, a point 

estimate of 0 .68 (95% CI 0 .32-1 .47), is not statistically 

significant . 


Lung Cancer in Nonsmokers 

OECtFFREY C . KABAT, PwD, AND ERNST L WYNDER, MD 

NOTICE 

This material may be 

ptote :ied by 

isw (TiUe 17 U .S . Gode) . 

Among 2663 prtieats with aewly diagnosed lung cancer laterriewcd between 1971 aa.d 19a0, 134 cases 

«ecvrred in ".alid.ated" .oascsokerx . The proportioa of .oascwkers among all tases was 1 .99k (37 of 

1919) for tsuo and 13,0% (97 of 749) for women, ririag a sex ratio of 1 :2-6 . KreybetY Type 11 (mainly 

asdetwcarrirsoeu) was more common among nonsmoking cases, espaialty women, tttan asnoa= all lung 

rocer tssu . Comparisoa of tases with equal numbers olaqe-, sex-, tace-, and Isospitil-tstatcised oaumoking 

eonerols showed no diRerersces by nligion, Fropottioo of forcigrt-born, saariai sntus, raideoce (nrban/ 

mrai), ako6ol coostrmption or Quttelet's Isdex . Mate eases teaded to hare Yi=her Froponioos of profes• 

sionals and to be wore eduated than controls . No differences ln occvpatioa or tsocnpatioaat exposure 

were seen in roen . Among women, cases were more likely than corttrots to La•t worked in a textiltrxlLted 

job (retati .e risk - 3 .10 . 93% confidence iater .al 1 .11-8b4}, but the signifiusKe of this finding 

8t not clear . Preiimitnry data oa exposure to ptissive itth+lation of tobacco smokt, a*ailable for a subset 

of tYses and controls, showed no diA'erences except for more frequent exposure among male cases than 

eontrots to sidestream tobacco smoke at work . The seed for more complete informatioa on exposure to 

s+ecoadhand tobacco smoke is discussed . 

Gtwter 53 :1214-1221, 1984 . 

NfA,e.cr,' l 

A LTHOUGH LUNG CANCER risk is strongly associated 

with cigarette smoking, lung cancer dtxs infrequently 

occur in nonsmokers .'-2 Several features distinauish 

lung cancer in nonsmokers from that occurring in 

smokers. First, most eases of lung cancer in nonsmokers 

are found in women .2-y Second, the d'tstribution of histalogic 

types of lung cancer differs between smokers and 

nonsmokers . In smokers the epidermoid type predomi- 

From the Divrsion of Epidemiology, Mahoney Institute for Health 

Muntnuna, Amenun Health Foundation, 320 Eau 43rd Stseet, New 

Yort, New York . 

Supponcd by National Cancer Institute contract N01-CP-056t4 and 

grant CA-32617 . 

Addras for reprints: Geoffrey C. KabaL rtsD . Divis+on of Epdemiolo{y 

. Mahoney Institute for Health Marntenancs. Amenan Health 

Foundauon, 320 East 43rd Stroet . New York, NY 10017, 

The authors thank the fdlowtnj txoqerauni ; institutions and individuals 

(or their a)uabk contnbuuons : Memonal Hoapital . Dr . Devid 

Schotankld; Manhatun Vetensn's Hotpttal . Dr . Norton Spritz; Long 

ktand-Jewish Hillside Medical Center, Dr . Arthur Sawitsky; Uaiversity 

of Alabama Hawttal, Dr . William bndrm; birmirraham Vetsran's Hospital, 

Ds . Herman F. Le?tman : Layota Uoisrsity Hoexul (Chica=o) . 

Dr . Walter S. Wood: Hina Veteran's Hospital (Chia=o), Dr. John 

fhup ; Hoeplta) of the U .iversity of Tennsylvania, Dr . RoEen M . txrin ; 

Jefferson Medical Collese and Thomas lofferson Univatity Hospital . 

C?r .1 . E. CotbtM Allegheny t'xneral HoepiW (FitttburYh), Dr. Sunley 

A. Eriller, Universiry otHttstwrfh Eye atxi Ear HoepW, Dr . Lewis H . 

Kulkr, rittsburflt Veurran's Hoapital . Dr . Eusenc N . Mym; MoRrtt 

Hospital (San Francisco). Univtrsity of Ca)iforni+ u San Francisco and 

County Hospital (San Francisco), Dr . Niehotts htnicir and St. Luke's 

Hospital (San Francisco). Dr . Richard A . t3ohannan . The authors also 

thank Ms. Marpret Mushinski for her collaboration in the exrly staaes 

of this study . Ms. Nancy Vrouoc for programming assiuanct, and Mr . 

Monte He+son and Ms . Mana Nanfiro for manuscript preparation . 

Acrcpted for publipuon August 31, 1983 . 


1214 

nates, whereas in nonsmokers adenocarcinoma is more 

common, especially in women .2-s 

This article presents data from a case-control study of 

nonsmoking patients with histologically confirmed diagnoses 

of primary lung cancer with rtspect to histology, 

dernoQraphic factors, residence, Quetelet's index, alcohol 

consumption, previous diseases, occupation and txcupational 

exposures, and, to a limited extent, exposure to 

the tobacco smoke of others . Due to the small number 

of cases and controls on whom we have infotTrtation on 

passive inhalation, the data presente :d here; on that question 

are in the nature of prtliminary results . A discussion 

of previous studies concerning this issue emphasizes the 

netd for obtaining more detailed information on sidesveam 

smoke exposure and related variables . 

Metbods 

All txsa of primary cancer of the lung occurring in 

cases who reported never having smoked on a regular 

basis' were extracted from an ongoing case-control study 

of tobacco-related ancers conducted in a number ofcities 

between 1971 and 1980t and described previously .' For 

each txse, the hospital ehart was rc-examined in order 

to confirm the diagntuis and the absence of smoking ~ 

~_. ~s*+ 

• our definition of a nonsmoker was someone who had never smokedN 

as much as one tajarttte. pipe, or erfar ptr day for a ytar . 

t T1x ma'oAt otthe ases (+nd matctKd controls) were rnte,viewed X 

J Y 

at Memorial Hospital in New York City, . 30 of the 37 male asea andQ 

70 of the 97 femalc easa .

. Vo 5 LIING CANCER IN NONSMOKERS - Kabat and k'yndtr 1215 

. 

throughout the patient's lifetime . The histologic type of T .a.c ( . Hiuoloy,c Type of t-uns Cancer 

.unQ cancer was obtatned from the pathology report or 

an Nertt Smoken and srnokers 

the discharge summary for each case Those cases in whom 

Men women 

the diagnosts was not pnmary lung cancer or in whom 

there was an indtcation of smoking . even in the remote 

(No 1 (41 (No / (4) 

past . were excluded from the study . Those remaining in NeVcr emoken 

the study are referred to as "validated" nonsmokers . 

Kteybera type 1 13 (35 1) 20 (20 .6) 

A control was matched to each case on the basis of 

age (=5 years), sex, race (with 5 exceptions#), hospitat, 

Epidermoid/squamous 

(Jttc tt{l/ti .ant cell 

Krsyberf type 11 

13 

0 

20 

(35 .(1 

(Se .1) 

16 

4 

72 

(16 .3) 

(4 .1) 

(74 .2) 

date of interview (±2 yean), and nonsmoking status . 

Abenoarrinoma 16 (43 .2) 60 161 .9) 

Controls were selected from a large pool of hospitalized 

Alvealar 4 (10.E) 12 (12 .4) 

patients who wera interviewed over the same period as 

Miaed (Kreybers I /c 11) 

and undiRcrenuated/ 

the cases and who had diseases which were not tobacco- 

anapltutc • (10 i ) S (5 .2) 

related . The distribution of diagnoses among the controls 

was as follaws: men, 62 .1% other cancers . 24 .3% benign 

Tou! 37 97 

neoplastic disease, 13 .5% non-neoplastic discase, women, 5mokers' 

$9 .9% other qncers, 14 .4% benign neoplastic disease, 

25 .8% non-neoplastic disease . 

Krrytxrg t,vpe l 

KreyberT type 11 

Mixed (Kreybers I & 11) 

1111 

600 

(63 1) 

(31 .9) 

la 1 

219 

(52 .31 

(42 .6) 

All subjects were interviewed in the hospital with a 

sxandardiied questionnaire including questions on de- 

and undifferentuted/ 

anaplutic 93 (5 .0) 32 ( 4 .9) 

moYraphic factors, occupation, occupational exposurea, 

Total 111 : 652 

tobacco smoking, alcohol use . Quetelet's index (ky,/cm' 

X 10,000), and historti of tobacco-related diseases . Two 

• A mort detatled bceakdown by htstolo ; c typa n not Presentcd for 

smokers because this informsuon + .'u not codxd . For the nonsmokers 

different versions of the questionnaire were used over the 

10-year period, the first from 1971 to 1976 . and the second 

thts information vas tetncved tnanually 

from 1976 to 1980 . Differences between the two questionna 

.irrs included a longer list of occupational exposures 

msponses was smaller for the question "Does your spouse 

amoke'.'", since this question appearesd in only one version 

in the later version, and a longer list of previous diseases and since it was not answered by those subjecu who were 

not married, widowed, separated, or divorced (see 

Table 3) . 

Differences between cases and controls were assessed 

by the chi-squarc test for independence .' and by the Mantel-Haenszel 

extension test for linear trend .' Point estimates 

of the relative risk with test-based 95% confidence 

intervais were calculated following Miettinen's method .' 

in the earlier questionnaire (diabetes, Sout, bronchitis, 

emphysema . hypenension, asthma, pleurisy, pneumonia, 

bronchiectasis, and tuberculosis) than in the later version, 

which included only four questions on previous diseases 

(chronic bronchitis or emphysema, asthma, diabete•s, and 

elevated blood pressure) . 

Alcohol consumption was assessed in current drinkers 

and exdrinkers (combined) relative to never-drinkers and 

oxasional drinkers (combined) . Occasional drinkers were 

those who consumed Iess than I ounce of whiskey equivalents 

of alcohol per day ot beer, wine, and hard liquor 

combined . Alcohol intake was categorized into three levels: 

(1) never/occasional drinking . (2) 1 to 3 .9 oz/day, 

and (3) 4+ oz/day . 

In addition, a number of questions on exposure to 

passive smoking were introduced in an addendum to the 

main questionnairc in 1978, and the addendum was rcvised 

in 1979 . Thus, information on passive smoking was 

obtained on only a subset of the svbjecu, for men, 25 of 

37 ases and their matched controi .s ; for women, 53 of 

97 cases and their matched controls . This number of 

responses was obtained for those questions included in 

both versions of the addendum, whereas the numbcr of 

$ otu onenuW male case was matched to a white cYmtrol : two hisa.nic 

anrM t.vo oaunul femak nses wett matched to whitc controb . 


Results 

For the 10-year period, 1971 to t980, among 1919 

cases of primary lung cancer in men . 37 (1 .9%) occurred 

in validated nonsmokers . Among 749 lung cancer cases 

in women, 97 (13 .0%) were vYlidated nonsmokers, This 

difference in the proportion of nonsmokers in men and 

women is hiittly statistically sipifiant. X2(1) - 137 .21, 

P

1216 

C.wcfn March 1 1984 vai . 33 

TAu.f 2 . Dutnbuuon of IIursround vuiables hold for both KteyberY I and Kreyberg 11 types : the man 

in Castes tnd Convoli 

age for Kreybcrg I and Kreyberg 11 lung cancer in men 

Me n W omen 

c. ... c.. UIQ4 c..a cow U-CAS 

was 52 .8 and 53 .6 yars, respertively, while in women 

Kreyberg I had a mean age of 63 .7, and Knyberg II had 

a mean of 61 .0 years. 

(No,) (R) (W-1 W Rro .) (*) (No .) (i6) 

Age 

zs9 13 (35) 12 (32) 12 (12) Is (IS) 

l0-S9 11 (70) (2 (32) 26 (27) 24 (2S) 

i0 .•69 7 Q2) 10 07) 21 (30) 34 (~s) 

70. 6 (14) 3 (l) 30 (31) 24 (25) 

Teu! 37 37 !7 97 

RAfipo n 

hamani 2 (6) s (I4) 27 (211 34 (36) 

Cttnol,c 16 (46) 14 /s0) 31 (32) 36 ()1) 

Jrnsh Is (43) U (31) 3t (40) 24 (27) 

ou,n 2(u 3 (9) 0 (0) I (u 

TouJ 33 33 ~6 *b 

Yr ot .ducation 

1-II 3 (14) # ((6 .Z) 31 (392) 29 (299) 

12 7 (l6 .2) 11 (297) 23 (271) 31 (341) 

(3--IS 6 (21 .A) 1 (216) 14 (lS .!) 17 (lS .S) 

16+ 20 (u .1) 12 (324) 16 (17 ..7) Is (ls .s) 

Totil 77 37 97 +7 

Qxvp.ua+al auw 

t•raka,aul 22 (39 .s) 14 (318) i (L2) 11 (1I .3) 

slulkd 6 (11 .2) 7 (11 .9) 26 (21,U 33 (36J) 

SrmuJ

I 

hi4 5 LUNG CANCER 1N NONSMOKERS - Kabar and Wyndef 1217 

btr of ycars of exposure in textile-related jobs (16 years) 

of cases and controls Among the cases, the specific occupations 

were the following : one seamstrrss, two dressmakers 

. one sewing-machine operator . one assembler and 

yarnwinder . one dress-shop worker, two salesladies who 

had done factory work, one apparel manufacturer, one 

clothing packer, one typist, one washerette/housekeeper, 

one bookkeeper, and one housewife . 

Among the 37 male cases only a few (5) rrpotteG exposures 

to substa.nces of potentially etiologic interest. An 

electronics engineer had 35 years of exposure to cleaning 

chemicals: a designer had 25 years of exposure to chemials 

and acids and I S years of exposure to plastics and 

glues ; a director of sales for a chemical corporation (a 

chemist) had 12 years of exposure to chemicals and acids ; 

an upholsterer had 30 years of exposure to asbestos, rubber 

. and solvents ; and a machine shop attendant had 37 

years of exposure to metals . grease .'and oil . 

Among the 97 female cases, in addition to exposure 

to textile work reported by 14, few reported other exposures 

. The assembler/yarnwinder who reported exposure 

to textiles also reported exposure to metals for 28 

years ; a machine operator had 10 years of exposurti to 

tnetals; an assistant medical technicjan had 10 years of 

exposure to chemicals and acids ; a social worker had 5 

years of exposure to metals and welding~ art electronic 

prototype technician had 14 years of exposure to chetnials 

and acids, metals and solvents ; and a chambermaid 

had 23 years of exposure to ammonia . 

We looked separately at the small number of ases who 

developed lung cancer younger than age 40, eight men 

and six women . The occupations of the men included 

an accounting professor, an accounting clerk (who had 

been a teacher for 11 years), a neurosurgeon . a stock 

trader, a postal service clerk, a law student, a salesman, 

and a self-employed president of a supply company . None 

of the men reported any exposures . The female cases 

included two houscwives, an assistant mana ;er for the 

Ametia .n Automobile Association, an electronic prototype 

engineer (mentioned above), a telephone operator, 

and a high school teacher . Only the electronic prototype 

en=ineer reported any exposures . The distnbution of histologic 

types among these younger pses did not appear 

to differ from that of all nonsmokin= cases . 

Passive inhalarion : Of the 25 male ases and controls 

who wexe asked about exposure to other peopie's ciprette 

smoke at home, six male ases reported having been exposed 

compared to $controls (Table 3) . Eighteen of 25 

cases reported having been exposed to cirarette smoke 

at work compared to 1I of 25 controls,'Ttte difference 

ie just stuistically sirnihcant (P - 0 .05). Mantel extension 

test for linear trend in the frequency of exposure (four 

levels) in cases and controls gives a chi-square of 2 .88, P 

< 0 .005 . The number of male ases and controls who 


TAtt..E 3, Exposure to tassive Inhalatton Arnon{ a Subw 

of Cua and Controls 

Men Womer, 

Casa Controls Cucs Controls 

(No ) (S) (No .) (S) (No.) f %) (No .) (ti) 

At homc' 

Yu 6 5 16 17 

No 19 20 37 36 

Tout 25 25 53 53 

At workt 

Yes It tl 26 31 

No 7 14 27 22 

Tou) 25 23 53 53 

(P < 00-45) 

Spouse smokej 

Ever 5 5 13 15 

Never 7 7 II t0 

Total 12 12 24 25 

' Current e>

1218 CANCER March 1 1984 va 53 

our computer file of self-reported never-smokess, review 

of the hospital chart revealed that 13 were actually smokers 

or had smoked at some time, and 9 were not primary 

lung cancers. These 22 cases were excluded from the anal .• 

ysis . Confirmation of the diagnosis and nonsmoker status 

of the controls was carried out in the sime way as for 

the cases . For none of the controls was the self-reported 

nonsmoking status contradicted by information in the 

c3tan . 

The finding that more cases rave a conflicdng response 

on whether or not they had ever smoked than controls 

( 13 of 147 primary lung cancer cases compared to none 

of 134 controls) is of significance . This suggests that some 

lung cancer cases tend to deny a smoking history more 

than controls with non-tobacco-related diseases. In a study 

of the role of ciprette smoking in lung cancer, such denial 

of cigarette consumption or under-reporting, which may 

also take place, would tend to reduce the estimate of the 

relative risk . In a study of lung cancer in nonsmokers, 

the inclusion of cases with a smoking history (misclassification) 

would also reduce associations of the disease 

with other risk factors . 

Although we attempted to eliminate all smokers from 

among the cases and controls by using a conservative 

definition of nonsmoker and by excluding any subject 

with a history of smoking either in the questionnaire or 

in the hospital chart, it is possible that some subjecu who 

rrported never havine smoked actually did smoke at some 

time . 

The current study confirms earlier findings that among 

tifelonQ nonsmokers lung cancer is exceedingly rare, and 

that the more conservative the definition of nonsmoker 

and the more detailed the smoking history, the lower is 

the proportion of nonsmokers found among lung cancer 

cases.3 

Histologic Type 

As found in earlier studies, Kreybery type 11 (primarily 

adenocarcinoma) is more common in nonsmokers with 

lung cancer than in smokers and, in both groups, KrryberY 

type 11 is more common in women . The percentages of 

nonsmoking cases with adenocarcinoma in our study 

(43% of males, 62% of females) arr in close agreement 

with those from the American Cancer Society's prospecdve 

study (46% of males, 59% of fernales, L . Garfinkel, 

personal communication, 1982) . In view of the differences 

in design and method of selection of subjecu, this a ;rrement 

suggests that these percentages may be representative 

of nonsmoking lung cancer ases generally . 

Sex Ratia 


In our nonsmoking cases there are 2 .6 times as many 

females as males, even though the male-female incidence 

ratio for lua& ancer is 2 .4,'° and the male-fetnale ratio 

among all lung cancer cases in our file is 2 .6 (1919/749) . 

The larger number of nonsmoking women with lung cancer 

compared with nonsmoking men is presumably due 

to the h.istoricaliy higher proportion of nonsmoken amonQ 

women compared to men . Doll found no difierence in 

the age-specific death rate from lung cancer among nonsmoking 

males and femalea.' Similatiy, C'rarfinkel" found 

no difference in the age-adjusted lung cancer mortality 

rate for nonsmoking men and women . 

Case-Control Cornpartsons 

Prrvious dueascs : Our finding that female ases had 

a hi;her frequency of previous history of pneumonia 

compared to controls is difficult to interpret since we do 

not have information on the age at diagnosis or on the 

duration of pneumonia . 

Occuparion Earlier ease studies of lung cancer in nonsmokers 

have included occupations in males with txposure 

to dust and/or fumes, i .e ., a carpenter, a joiner, 

a fitter, and a pour miller among the 7 male cases in 

Doll's study ;' two painters, a smelter, a blacksmith, a 

gasoline truck driver, agasoline and oil delivery man and 

gas station attendant, a cabinet maker, a sawmill worker . 

and an engineer among 20 male ases in Wynder's study;= 

a plumber/sitamfitter and an auto body and fender repairman 

among 8 male cases in the study by Wynder 

and Berg .' Among female ases, the occupations wcrs 

leis smestive of exposure to inhaled subsunces . These 

studies interviewed small numbers of nonsmoking ases, 

and did not make use of a comparison group . 

Our findings of a suti .stically significant threefold excts : 

risk of lung cancer among women who reported having 

worked in the textile industry is of interest . Doll, in his 

study of lung cancer among nonsmokers, lists occupations 

of more than 3 yeats duration in 7 male and 40 female 

lung cancer cases . Out of 31 women who had been em 

ployed outside the home, 5 had worked as seamstrrsse ; 

or dressmakers .' 

However, therc is no clear relationship in our dat ; 

between duration of exposure and risk of disease . Thc 

mean number of years of exposure was the same for cascand 

controls. Most importantly, it is not clear that ther( 

is a single exposure or group of exposures that all of the 

workers in textile-related jobs have in common . 

Furthermore, it should be emphasized that our o0 

cupational data are limited since there was room only tc 

code one occupation-,that of longest duration-and twc ~ 

exposures . Occupational and environmental exposures tc C 

specific substances were obtained by asking the subje,=N 

whether they had ever been exposed for more than a yea•~c 

to any of a list of substances . Self-reported exposures o .Q 

this kind are subject to information bias since awarenes,(A 

of such exposure could be expected to vary with the in}, 

~ 

~ 

N

No S LUNG CANCER 1N NONSMOKERS • Kabai and WwfdCr 1219 

dividual, with educational level, with different }obs, and 

between cases and conuols . In only 7 of the 14 cases did 

the coded occupation mention textile work . The remaining 

seven ases reported occupations not specifically 

associated with textiles, such as "typist," but reported 

exposure to textiles . Evidence from existing occupational 

studies of lung cancer risk in textile workers is 

scanL'3-" No cahon study of textile workers appears to 

have been a.rried out. 

The apparently minor role of occupational exposures 

in our male cases is consistent with the high peranta ;e 

of professionaLs (60%) among them . Altbough our data 

do not suggest an important role of occupation or exposure 

to specific substanca, it .vould be desirable in the 

future to obtain more detailed and objective occupational 

histories on cases of lung cancer occurring in nonsrnokers . 

Passive inAalation The plausibility of a role of passive 

inhalation in lung ancer can be questioned on several 

frounds . Although sidestrcam cigarette smoke contains 

higher concentrations of toxic components than mainstream 

smoke," it is diluted in the ambient air to varying 

degrees (depending on the size and shape of the room, 

proximity to the smoker, and ventilation) by the time it 

reaches the passively exposed person . As shown by Auerbach 

and coworkers," the changes in the bronchial epithelium 

characteristic of smokers are rarely observed in 

lifetime nonsmokers . 

Nevertheleis, the possibility that havy exposure to 

secondhand smoke over a long period of time could lead 

to increased cancer risk cannot be ruled out at prescnt . 

8ecause questions on passive inhalation were introduced 

in our questaonnaire in 1978, we only have information 

on this factor for between 28% and 68% of our subjects 

depending on the specific question . We present the distributions 

of responses to these questions as preliminary 

data since the numbers are small . Cases do not differ 

from controls except for the greater exposure to eijaretu 

smoke at work reported by male cases compared to male 

controls. Those cases who reported passive inhalation 

exposure did not differ in their distribution of histolotic 

types from unexposed cases . The ditference between exposure 

to ciprette smoke at work between male cases 

and eontxvis could be due to information bias, althoujh 

there is no indication of such bias in the responses to the 

other questions on passive inhalation . 

The studies which, to date, have addresssd the issue 

of passive inhalation and lung cancer have differed in 

methodology, the population studied, the type of lung 

cancer studied, the degree of histologic confirmation, and 

in results . These studies are summarized in Table 4 . They 

have been commented on by a number of investiptors 

." ."''• We wish to draw attention here to several 

poinu which are crucial in assessinj a eontribution of 

passive smoking to lung cancer and which need to be 


considered in future studies . First, the proportion of histologically 

confirmed diagnoses in the studies listed in 

Table 4 ranged from 35% (Trichopoulos a al (2G)) to 

82% (Chan and FunQ 1211) . Given the difficulty of diajnosing 

lung cancer, histologic confirmation is essent .ia). 

Second, Trichopoulos et al .i0 excluded adenocarrinoma 

and terminal bronchiolarcases, whereas adenocarcinom3 

predominated in Hirayama's easesu (personal commuttication, 

1981), in those of Chan and Futt=,2' and in our 

csses . In the American Cancer Society study reported by 

Garfinkel," histologic type was obtained for lung cancer 

cases during the first 6 of 12 years of the study . Seventy 

percent of these nses had histotofic confirmation but 

some of these were only identified as "arcinoma." Among 

the ases with confirmed histology and information on 

specific cell type, 46% of the male and 59% of female 

nonsmokers had adenocarcinoma compared to 23% 

among male and 46% among female smokers (personal 

communication) . Since tittle is known about the etiologic 

significance of different histologic xypes and since the 

distribution of types differs in different populations, it is 

premature to restrzct studies of passive inhalation to particular 

types . 

Third, although histologic classification of lung cancer 

is imperfect, it is desirable to stratify by the major histologic 

types in the analysis if the number of cases permits 

since differtnt histologic types may have different etiologies 

. 

Finally, all of the previous studies used the amount 

and duration of spouse's smoking as the measure of exposure 

to passive inhalation . Focus on the spouse's smokin; 

may fail to provide an adequate measure of the subject's 

exposure for a number of reasons : (1) a subject's 

actual exposure depends on how much time the smoking 

spouse smokes in his or her immediate presence ; the 

spouse could be a heavy smoker but spend very little 

time at home ; (2) in addition to the current spouse's 

smoking habits, those of former spouses may be equally 

important; (3) the subject may live with other relatives 

who smoke ; (4) exposure to tobacco smoke at work can 

be a substantial proportion of a person's exposure ; (5) 

exposure in cYSS, tommuter trains, buses, and in other 

situations, such as restaurants, movie theaters, etc, eould 

be sitnificxnt It is for these reasons that we have recently 

revised our questionnaire to include detailed questions 

which will give a more complete picture of the subject's 

exposure, both in respect to diffcrent environmental aettings 

and to duration of exposure for each specific component 

. 

If passive inhalation in nonsmokers is associated with 

increased lung cancer risk, by what mechanism does it 

exen its effect? Since adenocarcinoma is the most common 

histologic type of lung cancer in nonsmokers, one 

could hypothesize that inhaled sidesttram smoke increases

, 

1220 

GNCER March 1 1984 

TaaLE 4 . Summary of Studia of the Rolc of Rsssslve Inhatation in Lung Canccr in NonSmoken 

Author/ 

type of siudy/ 

population No of asss Histology 

Hiryyama (t9a1 174 datlu in marncd Out of a sampk of 23 aaes_ 

fropecu .t/ r«oaxnoicia` .roenen 17 were adenoarrieoma 

lap.nesc w/)unb a amonj 

twnsmo k i n6 9 I .340 nonszrtokt nt 

..iva atKd 40+ wrr+ed +oomen 

yClan 

Garfinkel (19{l)" 195 daths from lung a 

Analytis oa dlta among male 

from two twnsmokers: 56A 

pxospmtve daths from lung a 

txudies/ACS among female 

population and tsonamolcen (ACS) : 

Dom study of 168 lung a deaths 

vetersns" among nonsmokers 

(Dorn) 


Histdots SC . Ho HC, lronthial aaar in 

the risk for this type. Volatile components of cigarette 

smoke, including volatile nitrasamines, are more likely 

than respirable particulate nutter to reach the periphery 

of the lung . Current 6ndings suggest most lesions in nonsmokers 

are located in the deeper portions of the lung . 

Nonsmokers exposed to ciprette smoke in enclosed 

spaca are reported to have increased levels of carbon 

monoxide in their blood,"2s which su=esu that other 

F'indinfs 

A dae-rssyonae esiatiooshtp 

.as aten herwven the 

iocttmoking wivts' titah 

aad ahe kustxnds' 

amokirtr Mab(t wives of 

tatenoktn or of 1-19 

dss/day-unokers bad RR 

- 1 .61 : Wi .a ot unoken 

of a20 eies/day had RR 

•2.0b 

No aigni6cant iactsax in 

lun/aftskfeenin 

aasnmokinb wi .es of 

amoking husbands 

compared with 

aonsmokintt wlvss of 

monsmokink hustxnds 

RR of lung a associnted w/ 

Mayin= a husb.nd who 

nrtsokes 1 pock/day wu 

) .4 . (xt for linear trend 

• 6 .45 : P < 0.021 

Amon4 t+onsmokins women 

the prnponton of ases 

whwe >tpouae tunoked 

was slightl,v krwer than 

that o(contro(s (34 of 64 

or40 .S1,n66of139or 

47 .3%). Among 

aonsmokin ; women . 

there was no aqnificant 

diRettnce in the 

proponion of ases who 

wed kernoene fueltn 

Cookin; compared with 

tontzols 

Hotit Kong 1976-1977, Ir J Csnct* 1979 : I9 :1t2-t92 . 

Commenu 

Exposurc tadcx was, 

based oa tmok nt 

hab+u of husband : 

Exposure index wu 

duad on smok nt 

habtts of husbanG . 

Exposurc tnbex was 

brxd od unottn4 

ha.biu of kusMnds 

and former 

husbands 

It is uncku what 

quesuon .as uied 

feprdins 

inhatauon since in 

an earlier p.peY . 

the quesuon it 

pren at'Art you 

exposed to the 

tob.eeo smoke of 

oehen u Mome or 

at wo .k?' ; 

whCrru here 

reference is madc 

only to -smoktnt 

Mabiu of spouus " 

No tnformauan ts 

yven on how 

many sub~etta 

wors tturned 

N 

volatile components could reach the lunii . It would be C 

important to know in this regard whether the loation o!n 

lesions in the lungs of nonsmoking lung cancer cascs with C4 

exposure to passive inhalation differs from that amone(Z 

smokers. ' CA 

In addition to the etiologic factors discussed in this}A 

artick, other possible explanations of the occurrence ofCA 

lung cancer in nonsmokers should also be considered .0 

W

t 

Exposure to ionizing radiation in the course of radiation 

tre.atment could be responsible for some caxs . Also, 

Auerbach and cvworkers28 have suegested that lung cancer 

could arise in nonsmokers secondary to hei.led tubercuiosis 

sraas, althou¢h this is unlikely to atcount for many 

cases.z' Another possibility is that lung cancer in nonsmokers, 

es ;xcially adenocarcinoma, is estroQen-related 

since it is more common in women than in men . It has 

been shovm that adenocarcinoma of the lung frequentty 

conttins estrogen r>:ceptors .n Still another possibility is 

that a.rcinoQr.ns of nutritional origin could be carried to 

the lung by the blood . These possibilities deserve epidemiologic 

exploration . 

REFERENCES 

1 . Dall R, Mortality from lung cancer among non-smokers . dr J 

Cancn 1953,7 :303-12 . 

2 . Wynder EL 7obacco u a cause of lunt ancer, with spaial referena 

to the infrequency or lung cancer among non-smoYers . Pennsyavania 

Med J 195A ; 57 :1073-1083 . 

3 . Wynder EL &rj Jw. Cancer of the lung among nonsmokers 

Speaiiv referrnee to histoloyc panerns Cancrr 1%7 : 20 :I161-72 

4 . Vinant RG . Ptckren 1V.', l .ine WW et a/ The changint histopathololy 

oflunY ancer. A review or 1682 cases. Cancer 1977 ; 39 :1617- 

1655 . 

S . Ru!!x P, Hinch A. Maruau D, btanon J, Chreuan J . Etude ettolapque 

et hata4aypue de L4fi etncen du poumon . Ann Med luem 

1981 : 132 :12-13 . 

6 . Wyndtr EL StelJman SD Comparative eaidernioJogy of tobamc 

. Cancn Res 1977 ; 37,4608-4622, 

7 . F1nu JL Statisiinl methods for rates and proportions . New York : 

lohn Wiiley and Son, 1981 . 

1 . Mantel N . Chi-square tests with one dqnx of freedom : E :tension 

of the Mantei Hsensul procsGure . J Am Stat Assoc 1%3, 59 :690-700 . 

9 Mieninen OS . Ewmability and ewmation in ptt-refcrent saudtcs . 

.fm J Epsdemiol 1976 ; 103 :226-235 . 

10 . Amuican Canxr Socuty . Facts and F"Kures Chtato : ACS, 199 1 . 

11 . Garfinkel L Time trends in lunt anecr monality among nonsmokers 

arsd a nou on passwe smokint . J Nml Cancer Insr 1991 ; 

66 :1061-1066 . 


LUNG CANCER 1N NONSMOKERS • Kabat and Wynder 1221 

.reLted cancers 

Vllter Symposium : Lymphomzs 

12 . Nhlltamf RR . Stelent NL Goldsmith 1R Auoc-utions of ancer 

da arsd typc with oecupatton and induxtry fnam the Third National 

Cancer Surey instrvtew, J Nar! Cancer Insr 1977 : 59 .1 I


6

Kabat, G .C ., "Epidemiologic Studies of the Relationship Between 

Passive Smoking and Lung Cancer," ToxicolocTV Forum, 1990 Annual 

Winter Meeting (transcript) : 187-199, 1990 . 

In 1990, Kabat reported preliminary results from an 

American Health Foundation case-control study, which then included 

90 cases and 247 controls . Kabat reported that "preliminary 

analyses of the data do not indicate any striking ETS exposure 

differences between cases and controls ." Specifically, he reported 

odds ratios for men of 0 .98 (95% CI 0 .46-2 .10) and for women of 

1 .00 (0 .49-2 .06), for reported workplace exposure . The risk 

estimate for males is negative, and that for females is the same as 

the baseline, "no-risk" level . 



TOXICOLOGY 

FORUM 

1990 Annual 

Winter Meeting 

February 19-21, 1990 

L'Enfant Plaza Hotel 

Washington, D .C . 

JllP; 2 ": 199D


1990 A.nnuai Winter To)dcology 1"'orum 

L'Enfant Plua Hotcl 

Wuhi.agton, D .C . 

Fcbruary 19•21, 1990 

AJI rtiphn r.wnv*d . No portion 0 thn tranacript may ba r.produsrQ u utiuxsd in any form or try any m.ant . 

•Lcuonk or m.duniul, k+dudlrp al.ctorutic or phomoopy{np, rewrdinp, hfonraauon ttvape or r .tr'aval tytumt, or 

Oomputart, .fCSout prior parmitsjon In vrrttlnp hwn V* btrd ol Dirtepxa Hf Sh+ TtuJoojoqy Forum . 

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 

avfiltbIt nowhsrt .lu aa K h ananpad Mrain . Akhouph tM ooll.ciiorn antl oompllati~ pl (rtformaUon haf b .an cu .1uuy 

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 

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 

ToxioGoqy Focum, Inc ., 15TS Eyrr CtrNt, N .W ., w 6oot, WaMlnpto~, D .C . la.Y~6 .

CONTENTS 

Monday, Fcbruiry 19, 1990 i, 

Sessioa I•APPROPRIATEN-7E$S OF ASSUMING LO'A',DOSE I .IN'EARITY 

- E, 

C)R SECON-DAR)' C_ARCINOGE45 

Cbiirman : W . Gary flamm, Scienct Regulitory Syucros Intemational, DC 

IMPA t^'f OF ADD1TT1?TY TNEORY TO REGU.LA TORS 

Rjcbud Hill, Environmcntil Protect .ion Agcncy, DC 2 

DISCUSSION 10 

STrlTIST1CA1. ARGUMEh75 

Danicl krewsk}~, Hcaltb ind Wc1lue, Canada 11 

STA77ST1CtL ARGUMEh7S 

Tbomu B . Starr, Environ, VA 21 

DISCUSSION 


131OLOG/C4L ilRGUMEh7S 

James A . Swenbcre. Uaiversiry of Nortb Cuolina, Cbapcl 1-iill 3Q 

DISCUSSION -05 

BIOLOGICAL ARGUMEN7S 

R . Micbact McClain, Hofiman•l .a Rocbe, lnc., NJ ' 67 

PAN'EL DISCUSSION 

Chairman : W . Gary Flamm, Scieacz RcguJator3• Systcros lateraatioai .l, DC 

David V+-' . Gaylor, National Ccatcr for ToxicologcaJ Rouuc .h, /,R 62 

LUNCHEON SESSION 69 

Sess{on 11 ./X1MUM EXPOSED lh'DIY1D 1 r . 

Ctuirman : Paul Portncy, Resourcu for t .6c Future, DC 73 

GElJER4L CONCEPT'S 

Joha Grabam, Harnrd Scbool oi PubGc HcwJth, MA 

. 

74 

t~ 

GRT77QUE I• PUBLJC HF.rl1.TH PERSPECTTYE 

~ 

Beraud Goldstcin, EcviroameataJ & Occvpu6onsl ~i 

Hc .Jtb Sdcoaet lnuitute, NJ 90 

Pag= 

I 

.'.5 

GO

CRI77QUE 11 - EXPER1LfEN?A1,ISTS P .r.RSPEC77VE 

Aagclo Turturo, Nationtl Ccnter for Toiocological Rcuucl, AR 97 

DISCUSSION 101 

ASSESSING TNEA.IR TOX7CS PROBLEM USINGAMBIEhT DA TA 

Waam Hunt, Envirocmcntil Protc .uioc ~kgcmcy, NC 

DISCUSSION 


NEW LEGISl.4T10N ON .rL1R POLLUTION 

Robert Buatrd, Clcary, Gottlieb, Stcen & Hamilton, DC 131 

SOME TNDUGNTS ON MEl PR .FD1C77YE EXPOSURF ASSESSMEhTS 

Ncil H.wkins, Tbc Dow Cbcmiu] Compnny, MI 1.38 


U 

PaEc 

148 

128

CONTENTS 

Tu :sday, Fcbruar} 2 0, 

1990 

P age 

Session I1I - tI E FFF M O h'1v RO*1M DB D-h 

Cbairman : Gio B . Gori, HuJtb Poticy Centcr, MD 159 

REVIEW OF A WORKSNOP : ASSESSING 1.OW RJSKA GEh7S 

FOR LUNG CANCER 

Ragnu Rylandcr, Univcrsiry of Gotbcnborg, Swcdcn 159 

DISCUSSION 

ASSESSMEh7 OF EXPOSURE 

Nanry Haley, Amcrican HcAltb Foundatioa, NY 170 

DISCUSSION 


EPIDEMJOLOGJC STUDIES OF THE REUlT1ONSNIP BETuE'EN P.lSSIVE 

SMO~JNG .4 ND L UNG CA NCER 

Gcoffrcy Y,,.abat, Amcricus Hcaltb Foundation, h'Y 18, 

DISCUSSIO?: 2(R? 

INYOL Uh7rdRY SMOKING Ai .'D LUNG CANCER 

Lavrrcnct Gufiake~ f.merican Csncer Socicry, h'Y 20 . 

DISCUSSION 2,^,5 

R.ESPIRATORY EFFECTS 

Philip Witoritl, Gcorge WisDington UnivtrsSty, DC 209 


XE.iRT DISEASE RISK IN PASSIYE SMOKERS 

Daic Saadtcr, Nationil I :nstitutc ot Ecviroamental Hcakb 5c3cnaes, NC 2Z3 


CAR,DIOYASCUL.4R EFFECTS 

l .awtcacc M . Wcxler, New York Medical ColJege, NY 2,35 

DISCUSSION 2A5 ~ 

~ 

~ 

~ 

~ 

~ 

sv 

167 

16-i 

~ 

~

Sesstop TV: jIDTECN^tDLQjjT • RFPDRT DF A PEER R`~? 

Chairman : Ricbard Ronk, Food and Drug Administration, DC 

GENE:R.iL OVERT7EW. TNE PURPOSE AND CONTFh? OF THE IFBC R.EPORT 

Richard Hall, lnternational Food Biotechnology Council, DC 3 4 ;- 

SAFETYEVALU.lT7ON PROCEDURES IN 7NE IFBC REPORT 

lan Munro, Canadian Ccntrc for Torocalopy 232 

DISCUSSION 


ENVIRONMEh?,4L REVIEW OF BIOENGINEERED PRODUCTS 

Buzz Hoffman, Food and Drug Administration, DC 268 

DISCUSSION 2E3 

PR .lCTIG1L . EXPERIENCE IN RFGULfT70N PRODUCT APPROVA .1. 

Fred Shank, Food and Drug Ad.ministratioa, DC 2S4 


Pagc 

BOVINE SOM..tTOTROPIh' BST/BGH 

Gerald B . Gucst, Food "d Drug Administration, MD 295 

FOOD SriFETYilSSESSMEh? FOR THE USE OF BST IN DAIRY COWS 

Brua Himmond, Monsanto, MO 299 


THE SAFETY OF FOODS DEFtIVED FROM TRANSGENIC AN1AiA1 .S 

DsYid Berkowitz, U .S . Dcpartmcnt of Agriculturc, DC 316 


CONSUMER AND CONGRESSIONAL V7EW POINTS 

Lesley Russell, Committec on Encrgy and Commcrce, 

US . Hotuc of Rcprescatativc4 DC 332 


247 

263 

~ 

~ 

iv ~ 

~ 

~ 

~ 

~ 

~ 

~

Wednesdsy, February 21, 1990 

Sessloo V: $FS ATORX,u A S 

CONTENTS 

Cluirmaa ; Robert 7 . Scheuplcin, Food aad Drug A .dmia.istration, DC 

PD& C R.ED 3 

Roben J Scbcuplcin, Food a.nd Drug hd.miaistration, DC 337 

DISCUSSION 

DIOXIh' IN PAPER PRODUCTS 

Dwain L . k'intcrs, Env'uonmcntal Protection s.gency, DC 3-1,0 

DISCUSSION 


PROFOSTT7ON 63 

L.aureo Zcisc, Department of Ncalth, CA 349 


NC! UPDr(T'E ON !Q (2•AMINO-3-METHYL.IMIDr1ZO (4,5-F) QUtNOLINE') 

Richa.rd Adamson, NatiooaJ G.aur ]nstitute, MD 357 


RISKriSSESSMEh7AND TN£ Fi'rtXM.tNPEST7CIDE BILL 

Mikc Taylor, King & Spa]ding, DC 367 


THE BENZENE DECISION 

Jeanette Wiltu, Environmental Protcction Agency, DC 373 

DISCUSSION 3g8 

v 

Pagt 

337 

339 

345

DR, KABAT : Thaak you . 

The problem of pusive smoki4 and lung eaneer hu provoked a good deal of debste botk 

on a scicntific tnd on a public poliry level, Do the ctud ;es tlut purpon to sbou am assoei~tioa of 

exposure to environments] tobacco smoke (ETS) snd lung caneer occurring in lifetime aotumokers 

providc adequate evidcnce to resalvc the issue? As Naacy Haley has just ebo ..rs, zbc and bet 

eollca.gues s.re very good at measuring recent ezpcswc to ETS uuing eotinine measured in etliva, 

serum, and u,rine . Unfortunately, tbcsc biomarkers ue not belpfiil for asscssia~ exposure over tbc 

sevcril deeades relevant to tbe induuion of lun .g ea.ncer . Given the lack of a biomuker for loagtcrzo 

ezposure to ETS, epidemiologic stvdies havc had to rely on ssl!•reporu or prozy•repQrts of 

ETS czpc>stuc . 

I propose to raist F hat I eonsidcr to be some of tbe key aspects of the roujlJ ; IS 

epidcmiologc stud.ics of tbe iuuc of ETS and fu .mg cancer and to poi.at out eertain ueu t.b : : rcqu!- : 

furtber study . I Mill I-iefl} refer to our owm study ..,hicb is sti.lJ in proYress at tbe Amcri :a: Hca: :~ 

Fou.ndation . FAnall), i wilJ stsggcst a possible d'ueaion for furtber stud7 of tbis iscuc . 

EPIDE1.ilOLOGIC 

Table 1 lists studies cumi .t:inE tbc lung eafleer risk of non•s .mokiag vrivcs of smok.ing 

btubi.nds eoWpued to the non•smoking wives of noo•smol ;iag busbinds . One notes tbat tbe 

grutest ms ;zitude of thc overall relative risk (RR) is 2 .1 . A .fter the Tricboposilos and Correa 

aud;es, the higbest RR is 1 .65 (Laas et al ) . The national Reseueb Couneil's committee on pusi%c 

smoking earricd our a meta-anaJysis of tbc erist.iag uud.ics in 1986 and eame up .ritb am overall RR 

of 134 (95e"ro eonfidenee inten•al 1 .18•1S3) (1) . 

In four out of the fu`teeo studies listcd, the overall RR is etatistiesll} tigaif~cani . 1A'bcn 

onc exuaines the diti by level of ezposurc, i .e ., aumber of eiguenes ptr day emoked by the 

husbi.nd slratified into two or more levels, 8 of the 15 ,studies sbow evidence of a dou•response 

rclatiotubip, 

MSTOLOGY 


Wben we look at tbc eftect of ETS exposure by histologic type, wn sts an interesting 

disaepttnry (Table 2) . Dalager et al . (2) and Pershagee et al . (3) sbow roughly eompsrably elevated 

odds ratios (OR) for squi~mous oeU and emaU ecll cuanomu eambines, but not for 

adenocua.noma . In eontJast, Lam et a1 . (4) obuined a sigaiftcant eI(ctt for adcaor.arinomr+ but not 

for squamosu cell eucinoma . 

Tbe rtsulu of Hir .yama's atudy (5) prestunably agee on this point .vitb those of l,am et 

a1., sioce the majority of bis lu,j eatnacr ease .s +s+erc apparently adcnocareinoma . . Tricbopoulos et al 

restslts (6) prestuaably wtigb in on Ibe side of Dalagcr e1 al . asd Pers2sagyn et al, since 

Tric,bopouloc s :clude.d adenocxrizoma and term .iaaJ brme6ia) zuciaocsa from t}seir aeries . 

Since adenocariaoma oceurs morc eommon}y 'sa never amokers thia ba smokers snd 

rencrally more cammoa}y in .romen than ia men (7), oat wotild ezpect t2tat itf .FI'S ezocxurc is an 

appreelable risk factor tor hm ; aaa.r, it is auooiate .d w?it.b sdenocudssoma, as wtll as posS.r'bly vritb 

o6er types . 'I1e ina>asiuenry ia the results to dule regardi.ng Li.uoloLy iadieates that tLis is one 

uea thit merus furtber uudy. 

297


ASSE$SMEh? OF DISEASE STATUS 

MisclissiGcation on diuase uatus occurs wbce diaposcs otber t .ban prinn cxscinotri of 

tbe luag are induded in tbe easc series or .rbeo a primary eancer of tbe lubg is iucluded among tbc 

contsols due to iu ksaviag 6one uadcteaed Garftakcl et &i . reponed that of 283 .+omcn listcd as 

luving lu.ag ea,nar in bospita, rteords but sritb no mention of tDeir having r .n;,aked, 36 (12 .")rc) 

tvrncd out to b.avc diWoeet oeber tbin Iuag eaacer wbcn the histologv .ras reviee+ed by one of thc 

autisors (8) . 

ln uud.ies in whicb kiixtotooc vcritieation of lt,tng ea .oeer is a eriterion for indusion in tbe 

srudy, mi«liccifiution tbould bx minimaJ . Nov~rcvcr, tiomc of tbe uudies listed in Table 1 wcrc 

lsc.king this for all cucs . 

lt sbouild a1so bc mcntioncd that ev=a vbca luag a.ncer is biuologacally veriftcd, it is 

posssble that t:omc eases judgcd to b~e pr~mary sa.nc.er of tbe lung arc aaually r~eeoadary io a cay :cr 

of anotber sitc that bas gonc undete.ued 

ASSF_SSMEhT OF E?t-FOSURP STATUS 

This is a geater problcm tbas asussment of discasc status, and for somc i .nvestigators it 

is tbc key problem of epidcmiofogic ctud .ies of ETS a.ad luag eanccr (9,10) . 

Misclassi.ficat .ion of esposure szatus un occur in a Aumbcr of ways . F'ust, subjects p~o 

bsvc t;mokcd for s.omc period of thcis lifc c.in be erroncously iacluded in a t;tudy of tacver smokcrs 

Se .cond, subjcas may uadcr•repon (minimize) or over•repon (inllate) tbcir ETS exposusc, or this 

may be done by proxies . A t.isird type of misrlassifrcauon ean occur .rben trome iadireu measu : c 

(zucb as .rbcther tbc subjea is maNied to a smoker or bow mucb t4sc spouse amokes) is tued as a :z 

iadicator of ETS exposure . The cffect of misclassificution oe abe estirnate of tbe RR depends on 

Wbctbcr thc m'tsclassification is random or diffcrcntia) (tbat is tystcmatic) . Random misdissiTic•a ;ion 

wilJ bias tbc estimate of tbe RR towud tbe taul .l, thus making an eFfeu, if tbere is one, more d ;uicult 

to dcteu . If misrJassifieation oa ezposurc differs ber*'cte eases asd eoatrols, tbe estimste of the RR 

ca.n be bi.ased eitbcr upwuds or dovrnwards dcpendiag on the d'ueuion of t .bc bi.as (11) . 

MLSclGJS(fica.rion of Acr1vC sr/loktrl a.t f1CYtr Jrrloklr3 . 

Garfinkcl and eo- .+orkers found that among lung eancer w .es ideatiTed as 'saonsmokcrs' 

or lacki.ng aay mention of t:moking in the bospital reeord, 40% vcrc revule.d to have smokcd up, n 

reinterview (8) . AJtbougb a detailed persana] interview yields more acGwatc ssnokiag histories tba: 

reliince on bospital ebarts, it is sti11 likcly that, evtn .+bcn eubjc= are diruxly intenicwcd and morc 

w*?bca various prwoes ase ttud, aomc miulsssification of ttmokers as ootumokers Dccurs . 

Let his argued that random misrlassificatioa of emokers as aoa•uaokers eouple .d witL a 

tendcnry of t:mokcrs to marry tsmokers eould account for the obscrved usocat .ion of aspousc's 

znoking and iace .ascd lung canr:er risk in non•smoking :pouses (9) . Lssuming a SCr 

ci •t~~~__iFiution of amok.ing subje.cts, a RR of 2D for aa .ivc smoking„ no truc eficct of passivc 

tmolìn& and a betwcen•tpotuc tmoking concordance of 3,

, 

Nuclassificorion of iclf•nponrd ETS rrposvre . 

fA study by Pron et a1 (12) suggcsts that mi .sclaisification of sell•reporrtcd ETS expbsurc 

may bc esaensivc . They examined tbc reGabiliry of ruponscs in 117 coatrol subjects who had 

puticipatcd in a study of pauive s .moking aad who "rc reinterticwc.d on average ciu. months later . 

Rcspon.ses to an initiaJ quesiion about ez;osurc to ETS (yes/no) wzrc morc rcliable for exposure a : 

bome than at work (Table 3) . Rcproducbility of quutions conxraing exposure to a spouse's smol .c 

(ycs/ao) .+as hith for bot.h szxts, .+ith the rel'ubiliry bein,Y generahy lower for otber (ami)y membcrs 

Quantiuuvt mcuures of ETS exposurc, Le, ntssnber "d duration of eacposures, .+erc genera-ll) less 

rcliable tha.n qualitativc (or dJcbotomous) mc.uures . In tcneral, non•smokers gave morc reliable 

iaformauon on ala parametcrs of ETS expostuc than tmokers . 

Unfortunatcly Lbc study by Pron et al, did no( ezamine the rcliabiliry of responses amoct 

rsscs u .reli as among controls . ln use•control uudiu part .icululy onc must be conccrveH that th : 

cisc's reporiing of cxposufe may be ialluenccd by his dia;mosis . in a study of lung canccr ouurri : t 

in non•smokers, this could takc the form of uses probing past exposures more intensively thas 

controls and ovcr•rcporting crposures to ETS, since some cases mxy feel compclled to find a .= 

czplanation for thcir diseasc . On tbc other h&nd, it is also po-uiblc that uses migDt minimiu thc ;r 

cxposures out of am unv .illi.ngncss to blame a spousc . 

Nuclissificarton duc to use the spouse'i trnob'ng hAbis . 

Using the presenc.c of a uaoking spouse as aD indicator of ETS exposure can lead to 

serious misr.tassif,cation of czposure . Based on a survey of neuly 3$,000 nevcr• and ex-smokers, 

Friedman et a1 . (13) reported that tbc seasitivity aad sperificity, of usin .g the prescnce of a cmok .inE 

spouse as a prcdiaor of actua) ETS exposurc .rerc quire poor . TD.irrynine percent of tacn and a7r;; 

of womeL married to smokcrs reponed zrro bours of exposure at home . Conversely,,9ric of mcn 

a.nd 41 % of women married to non•tasokers rcportcd aome ETS cxpostuc . 

COT.'POUTr'DING 


Confound.ing is another major problcm arex for the evaluation of epidemiologic studics of 

ETS and luag cancer and one tbat has reczivcd relativcly littlc attcntion . 

Scvera7 studies :uggest that a Yariety of factors could aa as cosfouadcrs of am ETS•lu .nE 

cancer tssooiaiion . Friedma.n (13) found that agc bore a urocg neptivc rclationship to rcponed 

It:.TS expostue . Hours per vicek of ETS expc,stut .vere associatcd with alcobol cotut,tmption, 

muijuana tut, being curreatly u,nmarried, aad, ia a U-ahape .d fashion, w&h'oo ccUeQc education ° 

Koo, Ho, and Ryiasder (24) ezamined a .v'sdc varicty of bchsvion of the non•smotiinF 

.+ives of smoking and tDOn•cmoking husbands in Hong Kang 7"hcy ooadudocd thzt in Pnual Vrives 

witb hus,bands .+6o bad nevcr amokcd had bcalthier bicatyks thaa w°ivu .ritb axokinj husbands . 

Spccifecally, tbc former tvere of higber wdocconomic ttitus, wTrc morc cansdcntious bousc%ives, 

ate bcner dicu, and bad higber mdices of family ethzsivsneu as well as bener lealth ut .itus . 

A tbird uudy,,by Sidney ct a1 . (15) reparted that dietiry B-r:rotcac iauke was 

tipiGcant?y lo+r+er in aon•tmokus eacpcxod to p:ui.t amokc au bame than in non•amokcrs *rbo were 

so( czposcd, after adjustmnnt for ag c, sex, ne :c, education rutui, body *eight, and aloohol 'sntakc . 

189

They coacluded that dicu.r~ $-ctroteae iatakc was a poccntiil coalounder of the retationship 

bc r%=n E7'S ►n d lung can cc r . 

Ot.bcr potcntiaJ ctrafounders includcd occupation, domestic radon czposurc, a histon of 

ezposurc to tbcrapcuuc s rays, and kcepin{ pet birds in the bomc . This tast is raised by a reccn, 

study from the Nctberlands wbicb found thit the oddi ratio for lizg canocr among pcople . bo kept 

pet birds in their laomc was 6 .7 (95efb conhdcacc intcrval 2-2 20 .0) afier adjtutment for active 

amok.ing and vitamin C intakc (16) . This trudy did cot aucss ET5 crposurc amoag the subject s 

THE AMERICAN }EkLTH FOUNDATlON STL7U Y 

S.inct 148.3, a srudy of ETS and lung carscrr in nevcr gmokers has bcca in progress a : The 

American Ncaltb Foundstion . All lung canctr casc .s intcrvicwe.d in the contcn of a largc, mu] :i 

antcr uud7 of tobacco-rclated diicasu wbo rcpon aever haviag s .moked more than out cigarcttc 

pcr day for a year are givcn a dr .uiJcd ET'S quutionnairc . 

for ucb case, 2 3 bospita:ized controls .rbo have diaf,moses not known to be associa ;cd 

vritb toba ;.co use and Who are a.ls.o lifctimc non smokcrs are intervicwe .d Controls t.re matcbcd to 

cascs on age (+/- 5 ye .ars), t41. racz, bospitaL, and date of intcrvicw (vrithi .n 3 montlu ) 

The items in the qucszionnairc include czposurc in utcro ; in cbildbood (spcciTic famiJ~ 

mcmbcrs wbo cmokcd, years of exposure and avcrage number of bours of ezposuse per da}, as : a 

subjeaivc rating of the intensity of czposurc), in adultbood at bome (specific family members w1c 

smoke(d), nu.mbu o( cpd smokcd by cacli, years of czposure, numbcr of hours per day, subjcctive 

raun.g of exposurc, and wibcrc a spouse smoked, vrbet,Scr be or the smoked in the b+..droom), in tbc 

+orkplacs (numbcr of hours per %=h., yws of exposure, numbtr of amokers wit.hin tcn fect of 

r,g cancer cascs and 247 matchcd controls. We plan to mntinuc rcaviting subje.as for tbc 

study in order to reacb a samplc siz.e of 150 cues. Table


yicld approrimatcly I50 maJe and 230 femaJc ncvcr tmokers, bascd oa cstimatss of tbc fre .quency o! 

lung c.a .nccr amooE nevcr imokcrs (25/,c for malcs asd 105'c fos fcmaJes (7(), 7ablc 7 tbows tbc 

sa.mplc aizcs aeczuv} in cacb 1proup (assumiag equa .l tumbcrs of cases and e :ontrols) to detcct RRs 

berwcen 125 and 2 .00, witb a ooc•taiicd aJpba of 5% asd 80% power, pvea various proponions of 

cxposcd controls . 

i4'bilc it is hig.Lly unlikcly tDat tucb a uudy would bc fundcd tolely to assru tbc effects o` 

ETS ezposure, tbc ttudy cotild be de44=" to make am imponant coatnbutioa to t,be radon•luag 

cunc.cr issuc as .+ell. Spc .dfically, ttud3u of domestic radoa expc>sure luve also tufferc .d from sma!I 

ssmpfe iuu and boYC produced .wriablc and uastable ulimatet of tbc tisk of radoa c"sure in 

aevtr tmolcrs . la addiuon, tbere is a oecd to better aucu tbe iateractivs cifcru of aexivs tmokinF 

and radorr expostue . Sincc ET'S a,nd radon crposure ue bolb risk factors for ltng =ccr, aad si : ;e 

one miy, eonfouad, or interaa .rith, tbe otbcr, a large ttudv designed to me .uure botb fauors as 

rcliably as possiblc would iuve cnosidcrablc sdcetific mcrit 

191

GTS Z SdGZOZ 

tabl e 1 

E viderrjiotogic Studies 

Prospective Studies Relative Risk 95'/. C.l. 

Hirayama (1981) 1 .63 1 .25 - 2 .11 

Garfinkel (1981) 1 . 18 0 .90 - 1 .54 

Case-Control Studies 

Trichopoulos, et ai . (1981) 2 .1 1 .18 - 3 .78 

Chan & Fung (1982) 0 .75 0 .44 - 1 .30 

. . 

~ 

Correa , et al . (1983) 

Koo, et at. (1983) 

2 . 03 

1 .54 

0 .83 - 5 .03 

0 .90 - 2 .64 


Kabat & Wynder (1984) 0 .79 0 .26 - 2 .43 

Wu, et al . (1985) 1 .2 0 .6 - 2 .5 

Garfinkel, et al . (1985) 1 .12 0 .74 - 1 .69 

Lee, et al . (1985) 1 .03 0 .41 - 2 .47 

Akiba, et al . (1986) 1 .48 0 .88 - 2 .50 

Datager, et af. (1986) 1 .5 0-8 -- 2-0 

Pershagen, et at. (1987) 1 .28 0 .75 - 2 . 16 

Lam, et al . (1987) 1 .65 1 .16 - 2-35 

Koo, et at. (1987) 1 .55 0 .94 - 3 .08

* 

dz-,3TSdGZ0Z 

Cell Type Related to Spouse's Smoking 

Study "Istologtc Type At' Odds Ratio 95% C. /. 

1?atager et at . 

(1986) 

* 

Adenocarcinorna 16 1 .02 4 .33 - 3 .16 

$quamous & Small 

CCell Ca . 

14 

* 

2 .89 0 .91 - 9 .10 

Other 18 1 .31 * 9 .48 - 3 .57 

t''ershagett et at . 

(1987) 

Squamaus or 

Smal! Cell Ca . 

20 3 .3 1 .1 -1 1 . 4 

Other 4 7 0 .8 0.4 - 1 .5 

Adenocarctnoma 131 2 .12 1 .32 - 3 .39 

Lam gt al . 

(1987) Squamous Cell Ca . 27 0 .85 0 .35 - 2 .06 

Adj"siL%d for gender, age, and study area . 


Srnatt Ceit C a . 8 3 .00 0 .53 --16 .9

3ource : Pron ot al ., 1988 


Tablc 3 

Reproducibitity of ETS Exposure Data 

Ouestlon Kap a value 

Ever lived 

with r .gular 

smoker? 

Ever exposed 

to smoke at 

work? 

No . of resident 

smokers? 

No . of job sites 

reported? 

Duratlon of 

r .sid .ntial 

exposure? 

194 

0 .66 

0 . 46 

0 .55 

0 .37 

0 .45 

~

zZsTsosZoz 


"istoiogy o4~ Lung Ca~~~r Amonq Never-SPnokers 

IGfales 

N ('/.) 

Fema/es 

N ('/.) 

Squamous ~ 5 (13 .5) 10 (18 .9) 

Small Cell Ca . 

Adenoca . 25 (67 .6) 26 (49 .1) 

Large Cell Ca . 5 (13 _ 5) 6 (11 .3) 

BAC 1 ( 2 .7) 7 (13 .2) 

Other 1 (2 .7) 4 (7.5) 

37 53

~ 

UZSZSQGZOZ 

Exposed in 

Childhood : 

~ Exposed in 

Adulthoodat 

home : 


No 

Yes 

., r 

Tahie 5 

American Health Foundation Stu~ 

Cases 

i 5 

21 

Ma/es 

Controls OR 957. C .f . 

36 

69 

1 .00 

0 . 73 0 . 34 - 1 . 59 

No 23 68 1 .00 

Yes 13 3 2 1 .20 0 .54 - 2 .68 

Exposed at ~ 

. 

Work (ever) : 

No 16 4 5 1_ 00 ----- 

Yes 21 60 0 .98 0 .46 - 2 .10

N 

v 

Exposed in 

Childhood: 

tzSTSOGzOz 

Exposed in 

Adulthoodat 

home : 

Exposed at 

Work (ever) : 


C ` 

Tab1e 6 

American Health Foundation Studv 

Females 

Cases Controls OR C .t . 

No 17 61 1 

.00 Yes 36 77 1.68 0 .86 - 3 .27 

No 18 4 5 1 .00 

Yes 35 97 0.90 0 .46 - 1 .76 

No 17 4 3 1 .00 

Yes 27 68 1 .00 0 .49-2 .06

Table 7 . 

Power Calcuiation 

Odds Ratio Percent Controls Exposad 

To Detect 

20% 4001. 60'/. 

1 .25 1616 1124 1172 

1 .50 419 303 329 

. . 1 .75 214 161 179 

~ 

2 .00 134 104 119 

SZ '-~'TS 0~'i207 

aC = 


.05 (1-taifcd) R - I


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as.sessing bcaltb eficcts . NationaJ Auderny Press, Washington, D .C ., 1986 . 

2 . Dalagcr NA, Picklc LW, Mason TJ, Corrca P, Fontbam E, Stembagcn A, Bufilcr PA, 

Z.icpJcr RG, Fraumeai JT . The rclation of passive smoking to luni unccr, Camctr Res 

46 ; 48084811, 1986, 

3. Pcrsbagen G, Hrubcc Z, Svcnsson C . Pauive tmokin.g in Swcdisb women . Am J 

Fpidcmiol 125 :17-24, 1957 . 

a . Lam TH, Kung 1TM, Wong CM, Lasa WY, Klcevcas M'L, Saw D, Hsu C, Seneviratne 5, 

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ca,nccr in Hong Kong Chi .ncsc womcn . Er J Canccr 56 : 673-678, 1987 . 

S. Hirayama T . Non-smoking wives of bcavy ssnokcrs havc a bigber risk of iung caacer : A 

study from lapan . Er Med J 282 :183•185, 1981 . 

6. Tricbopoulos D, Ka .land3di A, Sparros L . Luz,g cinccr and passive smoking• conclusion of 

Grcck stud~ . Lanctt 2. 677-678, 1983 . 

7. K.bau GC, Wyndcr EL . Lung canccr in non-Smokcrs . Canccr 53 : 121~-1321, 198: . 

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control study . 3 Natl Canccr Inst 75 : 463-469, 1985 . 

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6 : 517-524, 1987 . 

10. Lee PN . Misclassification of Smoking Habits and Passive Smokinb : A revicw of tbe 

cvidencc . Springer Vcrtag, Bertir„ 1988, 

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12. Pron GE, Burcb JD, Howc GR, Miller AB . Tbe reliabiliry of passivc smoking 2ustorics 

rcportcd in a casr-control study of lung ci .ncer . AM 3 Epidemiol 127 : 267-273, 1968 

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J Pub] Hcaltb 73 : 401-405, 1983 . 

14 . Koo LC, Ho J H-C, Rylandcr R . Litc-history wrreLtcs of environmental tobacca Mokc : 

A study on non-smolcing Hong Kong Chincu wAvu aritb tmokisu versus oon-smokiag 

busbands . Soc Sa Mcd 2b : TS1-760, 1988 . 

15. Sidney S, Caan B3, Friedman GD . Dictary intake of carotene in noa-tmokers rvitb and 

witbout pauivL tmokiq at bome . Am ) Epidemiol 129 : 1305-1309, 1989 . 

16. Holst PA, Krombout D, Brand R . For debate : Pct birds as an indcpcndcnt risk factor for 

lung canctr . Br Mnd J 197 : 1319•1321, 198b . 

199


7

Kalandidi, A ., Katsouyanni, K ., Voropoulou, N ., Bastas, G ., 

Saracci, R . and Trichopoulos, D ., "Passive Smoking and Diet in the 

Etiology of Lung Cancer Among Non-Smokers," Cancer Causes and 

Control 1 : 15-21, 1990 . 

One of the European case-control studies to assess 

workplace exposure was conducted on hospitalized women in Athens, 

Greece . Based on 89 cases and 118 controls, the authors conclude : 

"The effect of exposure to passive smoking at work was very small 

and not statistically significant (the RR between extreme quartiles 

was 1 .08 (0 .24-4 .87)) ." 


Cr.•C+ ...,-xC .y~. 1 . 15-S1 

Passive smoking and diet in the etiology 

of lung cancer among non-smokers 

Aana Kalsndidi, FGcl F.2tzanr=ni, Ivelly Voropoulou, Gwqc Bastu . 

RndDlfo Sa=a . aad 1}imiaios ?ricbopoulos 

(Received d 1! pri; 1990 : rec :ccd m revited jarm 1 M.7y 1990; :c:epted 3 Ala7 19901' 

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 

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, 

aad 1919 . 1N wre mirs.~od ia lxaor. ; d oese iaterie~et' . 91 .ers lu~ .ioe ; .na .=o4en lateat 1G0 iosaxuied qeuait rita xtturet 

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 

; . .+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_ 

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. 

.o erit>ras oi anT au.xiauun .+tn e,zfns to asxaoan= Cd utbu bouxheid acaibca . ud the rmladaa .itb eLPIwess M Ftuus rsakic ; 

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 

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)) . 

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~ - 

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 . 

with a dG airc dia .gaosis of lung caaccr fonaed the ase 

ut~ie:• Tbe basuirals induded all rhrcx nacgr hospias 

sà t{ris ua- mc oaly hospi=l for chttz diseasa in Anc=, 

aad %~e tarr_ largesr uaivetxity gsocal bospictls . Womea 

wmr iacludcd .rhm chesr .rss a posxcive bismlogic or 

,CqmlogY mmiz2zin ., or wa= 6rvocboscopy was caa• 

sdrred dia ;ncuCC of pr:maiy bromho6=ic nrcaorna. 

A torsl of 160 cua .czc idr^^ rd . Concrols wns 160 

.romca hospitalized in the ortaopedic dcgucmcac of 

the suxc bospials or the oe=zby bospiul for ortacpcdic 

disorders, w .obich mosi ac :idcnr esa from Greatc 

Atars and Lne sur:ouadiag .ren. ate ad.=iaed . Cont.rols 

wce rindomly u?ezud froa : thosc acimiracl virtia 3 

weei -- ;,: tac aa of a corztspaading cue uid 

bad to be 35 ycza of agc or ovc . Araong ncc concol 

.rors~, 10 : bad &ctura and chc rc-Aizing 58 had 

ots,cr ;riumacc or orrnopcdir condiriar-f . 

A1! esa a.nd coat:ols vcr inruviewc` in pe=n in 

tac hospiral wards, ss soon as a dcEnice diagnosis Mu 

by one of ffvc intc :viesvcs who nch intta• 

rie.rcd tae ssr~c proporcioa of ases an d cnntrols . Therc 

Wrse no rerur+ls azaong eascs but siz werc too ill cd be 

inrcvie++rd. Azaoag wnaals, 1L xc: in n eoadi:dn raar 

did nor pe.-=ir iacL-view, aad chrr_ rcused ca ourc ;d• 

pa :e . !n the iace:vie•as, paucsa .+csz sskcd to iacicuc 

in det:i? chcs lifelong smokiog iusrocia . their =osun 

m psssivc sraokir:g--aom thcu hwbac .cs, E.roc ot'tu .: 

house:zold membGS aad ar work'-as weil as a au~e 

of other d=ognphic . soeioezonosaic, and medial 

c:=rr-isda . Subjcc^s xcc also asked to estimau the 

avca,-c arquency oi mnsumosion (per moam, pcr wc--zr or pe 

: day), befort the onser of the presenc diseasc' of 

47 food iusns or be-resatr areTorie7, These itr.ns wcs 

srle.'ccd irom ar1 e>zcrosivc lisr of 120 irems . using the 

aii=oa rhas ttu aderred isr= should cover, collexvely, 

more :han 90 % of ti7e ia .rsltie of ent:h of the eaagyrnc• 

acag autriena as pel .l u of vinra.ia A. This citcricn•n.t 

rsz+blished oa iafnrmsrion firom coacrol rroups ia a 

nurabcr of ase-conaol srudies uDde :dcra ia Athens to 

rsplorc the rolm of diet in tbe aussttion of ance: u 

.Kriau sfrcn .t1 

Lzfatirac espoasse to air palludoa was maualled ia 

the analysss aa t3u basis of iafor~na aboar thc lifelnar 

rmidmial aad cnptoPmezzc addrrsa of all subjeszs . The 

art:as of residtace aad work we=e divided inm fire 

earrYoria acsv,rding to thair esumattd ourdeoc a'u-pollu . 

tion lrve4s . Fnr tize Greazcx At3xas uea, air•pollutioa 

tevals by bomugh wKZe akulased on the truis of rhe 

mcaa yea.dy m.cuu.rzmeaa (1983-tS) of smoke and 

NO ;, as record.ed ia 14 monisnria ; staricm dirpcrsed 

tlsrouihout the atea . A Linc for zcro i .ir pollucioa wzs 

dnv^n ar the highesc powa of the turrounding mounuias. 

Por eazh borou.gh, the alsuhud air-pollution Icycl 

w'3s t.~tt avt."7.t'C Of ttf .e n]eaAlrerAeats of the three nCZrc3t 


16 

:utioru . or the two nrurest and r,be tcro air•polluaon 

line, vcigbred by the inre:se of the disu : cc f:ora the 

borough's c=tr : to rhe mcasu.rtzmenr points . Boroujhs 

wcrc thcn dividcd iazo four cucgoria, amgory < being 

the morr polluted with dai:ly smoke rnlues fsequatir in 

esr~s of 400 µg/ra5 and acerory 1 br:nc the les 

polluced Yrith das7y pak-sxnokt ralua rusly escr.diAg 

100 µ¢/ms . Pan rcadentes in rural ar semi-urbaa arrss 

(populsrioa less t3n.a 10 .000) Mcre coaside:ed u 

a.rrgory 0, mbems past tssidences in other cides of 

Grcce war clissified in nuyories 1 or : according to 

the tccordcd or pttsi :med 1erds of zir pollur:on. F'ua::11y, 

fnr e9e .-y individuat, a time•wcig:crd st: ..~ :was e: :J1:ud 

avu=g 40 houa pr. wc-s worx :ag ri .:. : fr : individu_1s 

worSr:ag ourside the home . For housewivcs, their bocae 

rtsidcacc fo=cd chc oniy 6^sis for estizaa : :ng thcir airpolludon 

crrosure . Wbcn 211 si:bjcas had zwei; airpoiution 

cposius assexsed, rkry werr disciburcd iatz 

fou: r•roups based on ttc masgin_1 auuriles of trc air 

polluuon i : dcz dismibuuoa . Since it is possiblc rhu tae 

hospirl ! crc.7mcar ucas are l:rger for ance: paxients 

tnn.r: for paz:cats with minor f:artures and rmumu, the 

possible ait-poUutioa artocia~ns wce o .kci ins aceount 

oaly ia or~cr co eonzzol for possibie con .faunding 

(gccm .zed 'e .' eicnG tcauiae cusal eae,.= or rhmugh 

selecaon forc=s), and noc for asscsrzaeat of cuscliry . 

Amons tr : 154 asea, 91 hsd be= life-lont noasmo 

:rs (las ;han 100 ei=sresr3 in thcs a .aoag 

the:a, 4-4 were diagno3ed bisroloTically (38%), 34 

c?rologicu.ly (3846), and 13 (14%) rtuough bronchoscopy 

. Among the 145 conaols, 120 had bern liie•lon ; 

non•mokea . 7he analyus was cnc;~.ne3 to li:c•loa= notnsmok= 

. 

Thrce souxe of passi®e smoicing -mined in the 

prro= siudy we_•r : busbzmd's swakiag ; smoiiag of orhe+ 

household racmberr, aad crpostut ro smol;ing u worY . 

Ezposurr to husband's smohdng was conai~e.rorl co surr 

u the timc of marriag•c or when the husband statsrd 

smoking (whithever casnc secoad) asid to end when the 

busband stopped smokint or dled, or the couple 

sepas7ced (*hi.tileres ame Cissz) . Chaa .ge of husband vu 

considcrd equivalcsrt ta chante in tuubaad's smoki .ng 

habits, whescas sin ;le Wamen wcs eonride:ed aa 

v.acmgosrd to husband's tmokiag . Ye= of esposure m 

busband's smobinQ and av=ge numbc of dg•uertes 

smokcd daily by the busbaad wese scpantcly carained 

in t3u ana.l7sis., 

lsposurc to the smokiag of housebold mesabers oc}sc 

rha.n the heuband .ns assosscd by taulrtplyinr rhe yrsr : 

a worrsan livrd in eticI af brr bnmes thtouthout he : life . 

with the aumbe: of smo4cn in ehe correspondin ; homc 

(esauding a+se busba .nd) and by summiaF thcse produr . 

taZns . 5ubscqueady, all .romen we.ro disttibutcd inu 

four groups; one connining those who lud never bee :

Lrxl caucrsmaxj sow•rn .airrr 

1 c'Po'cd co ps .ssive smoking frora mcmbca af 6cr 

houscaold ; aad chree corrsponding to the rerriles of 

ino riucr bouschold espoaue . Finally . csposure co 

pusive smokiag in the wockplar_ rzs cilculurd as the 

cime•wcigfircd stua af expcsure co smc!!c in rca-ycor groucs), years 

of scinooiiag (quzndcuivcly), arld inu :vie•ar• (four 

I P nkug 6W LAra V=,d 

iacucazor varab(e : ) . Ad coaEdcnce inre: ras silov+II ue T,tk 2 pomb=m d 91 acc-i-ahaf .aac .-,c lung esscr aad 

95!'c irscemis . Analyses we-'e donc using the GLLM 1~ma~cl~ramp.rioon .ummin+e~dp~rarMresolss~wurc 

sruucal pzc>:a ;c (Numedral Algoruilru Groun lnc., ro i=K tA1O'iet (a-sQ a "d-) 

Rticse 3 . 197y) . 

Results 


Tab1c I shows cbe d'u ;ribucion of caaa and cooaob by 

selecteo-d dcmoYzphic chu~ia . Thcre ur ao 

sigaifirar differe=es Mich rrspccc to W . 7ea.u of 

tdzooling, cuneac ruideace aad =puion, crra chaugh 

ctsce nrisbles were concoUed for in subsequenc mula• 

ruiarc ualyses . Table 2sho .rs rhc disaibudon of om 

tnd coaaolt by sclecicd paramccea of cpnwrc m pass .i+~ 

okin 'jXer'r }i' c.idcact dut 

:i un~moki~ 6 auociatcd .'rch >aaasc~ti~ ."d oo but the 

diffsrcnces ox aoc 1srp essou{h to be iarerprenble 

.'ir.iroui concrollint for confourlding e»fcc=s . TaBle 

compara ctu diso:ibudon of cues sod conuols by llfdaoi 

aposum to rwcdoor air pollucion . Zbc two di>zxibunoox 

us slaaosc idencinl . Finnlly, in Tablc 4 the discriburioc 

olases znd conccls by btqucncy of coasumpcioa of 

spcrificd fnnrI xroups u,d nucicnc is pnwrnsed .'Ihe•re 

cs no clut .,r sutzexcive di$ucace ber.rorn cises aad 

conuoh mich rapccr to any of che indicaccd aurriticaiI 

ruisbla . ezccpc for cercais (P - 0 .04) sad fruin (P • 

0 .11) . Thc u.aciatian vich cercals is posievc but is aor 

biotogically , rcdiblc . is noc suppotud in the Ucmauc, 

Qw~ CLM c"Mis P 

Hwh .nd't aadca~ 

Ci~et~s~dsy 

~cra crmkcd 2{ (23 .9) ~6 /39 .7) 

:- :D y4 (31 .t) !9 (li,d) 0.16 

21-~0 21 (24 .1) 21 (t9 .0) 

17 .a) 

H' " c'oiOt'"= 

D"°L0t11 Gq'O"14 

k Xd-,w&U R 31 . 

73bk 3 . 0issbuaon of 9 i om•enarin( wacnre rrm lunl anccr and 

1:0 aon•wnotu= malparuan .vmca by iada oi )ifclnaF eziaacut 

ee .wdoar air peiluccn (V«a;u In pr+=4i--%=) 

Mr poUutioo indeY Caa CO .+aolt 

1u quaKilc: .etT b~ 32 ()5•2) .L3 (35 l) 

2nd q,arule. 10+ 20 (22 .0) 26 (21 .7) 

3rd quattilc: mcdrnu 11 (19 .!) 22 (11 .3) 

4rb quunlr- b.ija 21 (23,1) 29 (21, :) 

f (or (+aar accd - 0 .99 . 


Tabk 4• D'a(nbunoa of 9l con•mokir.t .omea w cn luc~ aaca .ad 

1a0 Ocn•anoc:a)( corn¢uaon .aaxn bv ipprmr.u: r.ar~ oa qurtSn 

0r a c! trcqucry uf xnn :macon of s~r. i c1 Eooa rtou p u d 

aumr_a (parrr.njo in pursmcu :) 

i,,kAe c =Liawd 

Food puup (Zuuri)a 1 ~:r 

.r wu.ear t(~l 2 3 4 (~ln) liresr 

cest 

l,c-~mi (prriotmed) 

u,n 22 (2~ . :) 

maacfr 3U (25 .0) 

p ., ucoe 

a~o aS ( :'• .5) 

coaau~ 26 (23 .i) 

E004 rta: ;r Qulr, :kn P fot Ytamw C 

0r ouuit-V 

1 (Lzw) 2 3 SfH~ni 

(usrst r LW 30 (3~,0) 

~ ;qnrrais .S : (tl,s) 

cscs 2' C19 . .'7 16 (17 .6) 34 (37 4) 14 (15 .4) 

tm=/s :i (35 .1) 3a (21 .3) 33 (27 .5) 10 (1 .3) O .Oa 

Os6c eao-umsolk Me.c~ 

acs 4d (4t .4) 30 (33 .0) 17 (11 .7) 

~ 69 (57 .5) 26 (21 .7) 25 (20 .3) 

V==n A 

ase 23 (21 .3) 21 (23 .1) 20 (22 .0) 2' (29 .7) 

maaau 30 (25 .0) 31 (16 .7) 32 (23 .7) 26 (21 .7) 

Tod rmerLry 

ca .v -' 3 (Z1 .3) 

convr.b 30 (25 .0) 

13 GS i) 231( :3 .1) ` : (27 .5) 

3P (15,0) 32 ( :6 . :) 21 (23 .3) 

. 

~oawa 

e-:n 

oorurou 

7 (7 .') 

14 (11 .7) 

)1 (19,3) 

27 (2'.,5) 

53 O1, :) 

5; (47,5) 

)3 (1 : 3) 

22 (11,3) 0 .37 is not p;rucularly r auai . u;d may veU bc 

by th e atlltiplit:iry of comparisons =aac : it sns n~ 

SuOsn 

fursiler ezploced. By 

corsnst, cbc ncguivc a0or'sti= 

q:cs 2Y (30 .3) 24 (:6 .4) 26 (].t .6' 13 (14 .3) with corlsumprioa o f %wi(s is bioiorically credibic liren 

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 

V 

ca&a 

osauol+ 

27 (29 .7) 

34 (2t•3) 

12 (24 .2) 

36 (30 .0) 

11 (19 .1) 

29 (24 .2) 

24 (26 .4) 

21 (17 .5) 0 .14 

tnd CODII'nli . 

The anocizxioa of 

lung cmcez wit5 ezpcrsum oo pusiw 

sawkia; through marrA(c la s>9sOking husbandr .u 

huia 

Euruler cramiaed by mukiple loQircc tsTrasioa, 

ooa 

sona.u 

37 (3t .5) 

:2 (11 .3) 

19 (20 .9) 

44 (36 .7) 

15 (16 .7) 

24 (20 .0) 

23 (24•2) 

30 (23 .0) 0•1( 

~ coaaolliaZ ~ for aje. )esn of ~, .Soolimj, lnd iarexiew-~ . 

~pc-maIIte Ctk ( U) COn3A7S1nx t.ntt= Miilitrl< 1G 

Haa. 5cti . .W 

a.a 26 (2t.i) 

toauaL 39 (32•5) 

23 (25 .3) 

27 (22 .5) 

21 (23 .1) 

31 (2S .i) 

21 (23 .1) 

23 (19 .2) 

i¢w}x.a .rixh 6" msaitd to non•smakra mu 1 .92 .'stf2 

Q 1.01- 3 .59. ' Th e CL:rea of slle avcrap out5bcr af 

0.57 djusrrrs m:aked daiJ7 

by the husband uld rhr dun>=aa 

1(IIk tod auLk pmduco 

a+a 21 (23 .1) 

cenuoL V (22 .5) 

29 (31 .9) 

32 (26 .7) 

14 (17 .i) 

30 (25 .0) 

21 (27,3) 

31 (25•1) 

of marria;e to smokens 

*crc evalulced in nro diirerrrr 

alodels, eoarrol.lin ; for the xme coce .asisbles ss :ba- 

0 .74 snd inuoducis2t, slrcraaci.elp, 

the daily numl+c: of t'~ 

drurnes anc3 rhc d untiaa of marziage u qusatincTe ~ 

Fan utd als 

tcmss inten.ui.nj with 

the smoking mrus of the husbxesi ~ 

ICUa 

mavnl. 

31 (27 .5) 

37 (29 .21 

2d (2~ .4) 

30 (21 .0) 

33 (lb .i) 

33 (27 .5) 

9(!•!) 

22 (11 .3) O ." 

(the 'rau' device) .l'- 

u Thc lung anca dsk amoag oow•tin 

irnokea inaesse d by 

16% fnc cYerf 10 )reaa ef el¢owir Q 

Ceh 

a.a 70 (76 .9) 10 (11 .0) 11 (12 .1) 

to 6usbaad'1 msoking 

ssd by 6X for r.eiy sdaic"fjj 

' padc of cipascs smokcd 

duli . Thae alinuces sre lo+~„~ 

tunrroh 95 (79 .2) 1s (13 .3) ! (7 .3) 0 .44 and sruistially noo- sitnif'lslnr - pcobably bcrause . WUrCA 

tu 

C.3 

~ 

0 .u 

0. : 

0 ( :29) 20 (aa,0) 27 (a4,7) 

55 (:' .5) 33 (2' .3) 2L i : : .') 0 .61 

16 (1 ; .6) a3 (as .i) r. (2 .~1 

3!( (31,7) 29 (24 .2) 31 (22•!) 0 .30 

=5 (S7 .)) !t (19 .!) 21 (JT.S) 

27 35 (27,2) 23 (23 .3) 0.93

52 

4! 

7 .1 

!,r 

.) : 

7M 

Ile 

1.u+t tsncer tr.onY aon•taolcrr 

Chc smoiuag sucus of dsc husbarld is rz:.idly asccrmiacd, lUU :llL 

.•i• 4J 14Uw iT1C111111gLW ' "'1CLLl UC Lil6Ci"uYC 

th e q,,,nhauve aspeuts Of thc esposure ue difficulr to el.iezis, if aay . 

The last mode ; vu also applied separuGy for adeoo- 

j~ey y,Ce'1Sr'aCely, 

5imitu modea ~r .r used to ssscss the e6ccn Of curinomu, an one hand, usd For squsasoL=, srnail• usd 

ctparutc to cobacm >znoking by ochos household mem- luqe-cdl raninomas, on tiae other, using in both inbcrs 

ot at the vorkphce . Tbc rmulc t.ere qualira>? .cly rcuces the total sez of conuols . The raults are sbown 

~rilir to those pcesrnteA in Table 2 . Ihere ru no in Tablc 6 . !c anpnn that the cEcra of inuivr smokin ; 

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- 

bouschold mcrs'ea• •hems the ettect of aposure to a .^•omas tahca tojr., :er . tha•n for adGOCUCi.oomi, 

passive sasokinQ u•osk was .crq szas!J and not stzrist- altt ougb c!s diac :=ce is eot sazs-icslly sirftii:rrm. On 

ically siguifictt (the RR btc .re= eza=c quartila .ru tsse contruy• the nutr'uotvtl facarts) assoazted with &%tic 

1 .08 (0 .r4 -i .87)) . CnaanUing for ur poUurion had no constunptioa appru m be equally strnng in boc~" gups . 

crr.r on any of the mulciva.âte anal,vses . 

Ta .blc j sho" trultiple logisriz tzgre9,ion•deaved RR Discussion 

for lung c-.ace: =or.g non•srnorea bc :wrc : ersemc 

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 

estimatcs are adjusced for agc, ycn of scbeoling, strongiy support a causal relat :on be:-cen pustve 

intc :viewe :, zLd total energy in : ke . There is licle, if snorci.ns ind lung ar:cer ."' ~a Ihe : have been zl .io 

any . coaiouncinC 5c .-Wce: the two indicated food groups more man 10 epIde :%ioiogic szudies uscui ;y c:.c role of 

(ve ;eubiez u:d i.•uia) or among d-e thrr. indicrcd nutr•.tion in the r.iology Of lung ca:.c :: . In a enttca) 

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 

vcgenblc, prot :: ag2inst lung aric : :, as:d that vitimin te :aarxably corsisrce in sL:qresdnY sn invnac association 

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 . 

assocacec wicn fr.:ic corsumpcon . The--e s ako evide nec ' t!~e discsc . Since botn espon:rn to passiNz smok:ag, and 

that rerrsol (prc-fomud vinm .in A), "ru from beinp a dir, pc>or ir fruit and veVta ..bles, mz'rr?e: inade_uuc 

protective, miy u:.a11,v be usociated with 1a int :eased heaha edua ::on, it is conncivablc Ihat e:ca of tite two 

risic Sor lur•,Q m:ces in this se : es. faceors could coaiour.d the te:adoa of che other to the 

Fia.aly, eposur: to husband's tobacco smoic :r:g, zad rislc of lung aace : . Tae preseat sasdy suptcre rh= tbiz~ 

fruic coor :rz:pdon were ss:usuluneously introduted in --I is aor the asc : the-ef&='of pattive smoYint attd die : 

anotiur model (toeethe: with ige . rrus of schooiing, r sppar to be itsdc^.,esd=trkt:sdual coaioundi .lg on cae 

inte.-vicwc :, and tocal cn e :gy inta.icc) to csplorc vhe-.he: basis of a conceivable as:ociation beârt-cn hr.tsbznd's 

the p-_ssive smoicing cicct is confounded by inadequate smokinf of hijh tar (ntae : than loa nr) aptertn and 

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 

In fact . we RR ~-i~ted .vith enposurm tn husband's hirh- and low•tar ctar-es coafe : simiiar saostses in 

tobacco sraoking inueased from 1 .92 to 2 .11 snd the the eoncext of pusive smokinQ (ru intaice dep=ds 

relItive tisk usodatd .rit'rs high u, low coostuspdon of ptir•arily on the filte : uscd) . Furthe . .^•,ore . the special 

huits deerascd frnm 0 . 33 m 0 .2' . lnaoductioa of eceals c-or, to escludc cx•smokcs hom the study of lung ances 

to the laft mui.el had ao effecs .iiereas the study was amony aon•strsokers pteridea ururaacc tfiat the surln 

Tab4 S, 4ulcpie lofnoe aTresiorrdrmcd reSare riyk fw istn{ noea 

unonj Ooa•emoiee benem aaeaie yunnilen .f rlecuc ~ud ~toups 

K LlC.tieltp 

tood jroup or 

liiacis rndc Coatidarct P nlw 

.""nt 

bKr.ees essrezae roanl• 

---~ ., . 

rl-c.ure" 

qv&ml-c' 

l .ot o.u_ l .sa 0.96 

lssimt(prr{artwdl 

Vux=a C o .s~ o.a- t .os 

0.06 

o.ot 

v.Yeflbin 1 .09 0 44- :,0! 014 

frwn 0 .11 o .ts-o .ia o.tt1 

'CancroUMf tnr a~c . .na nlunayint, iorw~s+.er, sr.d wa cecrTy 

Meyk~, 


Tzb1 . C Mutripk laruac w~emms.iev.ed adad.e tW (9)X 

eoandeece ia~) >bc Iu:C aocr, by b .M)otic s" anwnI ron• 

smuicr, urorriinl to 13ssbiod's eoCaao rmok .os runu U~d so lu(o 

n . bW tuartik oi fruie eseuumpuan, 

HsTaotial qpc~ Hubwi uaakr, 

a. ao"awJms 

All kaag aocsr 

nde,aocuabeta„ 

Syvsmar, sm.l1• r • 

kuir-cr0 

2-11 (1 .OV-4 .ap 

:.SJ (O.Yt-7.)7) 

Fn:io cusumpuac 

h46 er . Sar qwrcle 

o . :1 (o .1A - 0 . 7 4) 

O .1a (0 .0 4 

{uettallieR fat agc . re•us Of s&Ml;nK, mur.iesr. usd roaw cncrp 

Ltetk i . 

4of :i of tfu it eua 6i,+olo" rope vaI na i .n,ublc . 

19

nsivc ~ 


aaoSci.oj znd histolo8ial rypa in lunj ancee it HoaB 

Kon( Chincx wcxnen . Br f Gsur 1917 ; S6 : 673 - i . 

6. }:oa LC. Hc JH-c . Saw D, Ho CGF. M-1- aa oi psarrc 

smckia{ u:d estimua of lunf mca risic uaortt aoatmokio 

j Chinc-3c feasla . !sr f C,usus 1917 ; 39 : 162 - 9 . 

7 . Gw Yr . flloc WJ . Z'hmg m . is al. Lunj eaaca ataoa{ 

Chincx vor2crt. l.f J Ga+sn 1997 ; 40- 604 - 9 . 

1 Inouc 1. Hiuysma T . Pos;ve saoLiaj snd tun8 cacica 

in wmea• 1a : Aoki N, Hiuraicai S, Tomi .up S, cis . 

Smo,Fbs od Nealcb 1987, Atasscrdua : lssc^cc n~cdin 

19ye : 2J3-3 . 

9 . Cxn GY . L'ung 2H . 2hsa5 AY . Wu GL Oa cu rchronrhip 

bc:.rr.c smokin j snd fc :nale lunr atcct . ln : Aoki 

U . Huamiciti S . Tornicuyz`S, eds . Srco.Ersj d Hcr[tb 

1987, Amstr.e:r : Es:e:pc: ](edia . 1988 . 483 - 6, 

10 . Shimizu H . Koruhin M, !lirano K, st d . A au caauol 

r.udy of lung cuscc: in non-ralokin j wroca Tonoex J 

Exp Mid 19Ytl : 154 : 389- 97 . 

l l . f:aeauyznni K . a'illetr W, Txichopoulor D it sL R .i•tk of 

breu: anr. : zmoo( Grce3 vo©cn in ts'stion w nucnent 

incake . Gr.ur 1961 ; 61 : 181 - 5 . 

tz . 1Lcmncn OS Ti.orzncal~rJ.~17 . Nev Yoric : Wilry 

blcdical• 085 : I16 - 44 . 

13 . Tcc.':epoulos D, HsicS,C .,1( :cJtahoa 15, it sL A.ec u say 

'sittth snd b cn :a csncc: risk . tsr J Craars 1913 ; 331 ; 701- i . 

14 . Nuiorul Resratc5 Council, Commicccc on Pcui.e 

Srnokia j . Errvorrn.n+Aa! Tovu:.ca Ssrole : Mrarurrrt . 

• Erparu .rt o+d .iuis.rs„j Hralib E',ficrr . IS/aabinr :oc LK• 

Nuional Anduac Ptcsr• 1986 . 

15 . Sur ;cnn Gcnr.tl, Tqe Nakb Conuwi :.crf of Irx.Gr .ca7 

Smeiicy : : Ri.eon . llock~iLe• Msrylind : US Depus.:.rst 

of ticzlcb add Human Scr .ica, P•ublic Hcai ;.5 5s :vicc, 

C= :ea for Disrue Control . Cratc : for HcaJch Pzor.ucien 

snd Uuta :ion . OtScc on SmoEinj tnd Hci1tL• 1915 ; 

DHY-5 (CDCi 17 .i398 : 332 . 

16 . Wodd Hcaith Otqusizz:ion, Tobaao SmoEr'sj, LA•3C 

Monoftsphr on t6c EYaluuioa of the Camino jeau Aizk 

of Chcmrala to Hur.zas : Vol . 58 . Lyoa, Fnncc : 07orld 

Hcslth Orizntsacon, LkRC, 1986 . 

17 . C!lillect W . `'uuirionalEpialtnr.eku, New Yotk: Ozford 

Uaivearry Press, 1990 : 292 - 310 . 

111• Sut;con Genetal . Tbe Hrslrb Cox.utsnccsr ofS.o.4-ri.j 

Lnr j cnaen tncon j :o .-twca4rr 

jo . D'o=Ws: A R .parr . ixL .zlk, 1luyhod : L'S Dcps.-t• 

mc'tt oz Hdub and Huusa Servim, Public HaltS Sc .ice, 

OEfice of the Aswanr Sr_rrsrl for Hcalta, 0s cc on 

Smokinf and Healtti . US Gv .ammcnr Puncnj 0£'ice, 

1980 :0-3 :b-003• 

19 . Vem JE . .i :: pollvtioa sz s risk £car it lun3 arunr . A,w 

J F~ps.4,rsnl 1982 ; 116 : ,*2 - 56 . 

24 . Hiranei m, Iavciud Db . Sirtca 1fG, Lunr cuxsr 

motnliry u rciated to residcnce sad smoEint hi,mria . L 

Qjiirc tr-- :a . JNC! 1962 ; 23 ; 947 - 1001 . 

21 . Prs R . T,e mszcs-J diffcuaces bcnrecn tuvccnoids and 

rcrinoi,ij : metbodoloSical itapliacov for biocheaicaJ 

cpidr-:inlc87 . Csncer S.vs 1983 ; 2: 23 ; -40 . 

22 . D7atc:bc:y LW . icob WD . InhiDiiica d polyrytli .c 

ammuu hydrocrt:oo•induced ncr ;l :uis by auuaL7 

ocruuic8 indniu• C.r:ccesRrt 1978 : 31 ; 1410-3 . 

23 . S&co A . D"•Vorfis P . Skalkidis Y, Kaaouysani K 

Tnehopouloa D . .M dsslwio+e of tbr ~~urr.rsett of 

Tojaua-cosne! Lr ju4me Po(iciu o 1=C Me»eoer Suur . 

1941- 79d7. a rr?orr tc the Com ; ~n ar tat Jiavope:w 

Cot:nraunirus. AtIear : Furnpe lfa,nst Ciner., 1989 ; 

i41 -6+ . 

IS . :ussson Geae :zl. r2eliuraj rie NcsliL Conrreye,cut of 

Smoias• 1j Yssrr of Prorre .u : s&pon . Aodnille, 

Elar.iaad : US Deparr;a.car of HcJtti and 'tdurasn Ssrvicv, 

Public Hrlth Scnces, Centea for Disea,c CoouoL Cnce : 

:or Quonic Diacuc Pre+esci.oo snd Hclch Promoaoo . 

OE•- icr Smoicia{ and Hoalch, 19E9 : DHD-IS Publiazioc 

tCDC) 29-!•A 11 . 

25 . 6ro.naon RC. kcii JS . Kedc TJ . feqtyon SW, Psc! JA . 

Ls1t 6croa for sdcnoeusiooru of tbe luat . Am J 

E,ordes.~ol 1987 : 12i : 2$ - 34 . 

2G . Dals!.cr VA . Pickte LD7, Yason TJ u st ; The ralnrion of 

passive imokiag to lung ancer. Ca+c:r Rer 1996 : 46 : 

LlOt - 11 . 

27, Pcmhzca G . Hruber Z. Svracoa C . Pnnire rnaokins and 

dint aaeer in S .edish .amrrt, Ax f Fr~,r/e"tial 1917 ; 125 : 

17-24 . 

21 . Wu AG, Hcadcaoa 3E, Pikc MC, rt al. Smaki .ag and 

otDa ask fae:ors for lun8 ance : in .ornr . JNCI 1985 ; 

74 ; 747-51 . 

21 

i 

L


8

Koo, L ., Ho, J .H .-C ., Saw, D ., and Ho ., C .-Y ., "Measurements of 

Passive Smoking and Estimates of Lung Cancer Risk Among Non-Smoking 

Chinese Females," International Journal of Cancer 39 : 162-169, 

1987 . 

Koo, L .C ., Ho, J .H .-C ., and Saw, D ., "Is Passive Smoking an Added 

Risk Factor for Lung Cancer in Chinese Women?" Journal of 

Experimental and Clinical Cancer Research 3(3) : 277-283, 1984 . 

Koo and colleagues, in their 1987 case--contro7 . study of 

women in Hong Kong, included an assessment of workplace exposure in 

an accounting of total lifetime exposure to ETS . The 

concluded : 


On the basis of our extensive life-history 

data, we were able to calculate the total 

years, hours, mean hours/day, and cigarettes/ 

day to which the subjects had been exposed to 

tobacco smoke at home or at work . 

Despite such detailed accounting, we were 

unable to find a significant trend in the 

crude or adjusted RR for these 4 lifetime 

measurements of passive smoking . 

authors 

In a 1984 publication, Koo and colleagues reported a riskk estimate 

for women exposed at the workplace of 0 .91 ; this negative 

association was reportedly not statistically significant .

J . 

.1 . Ltp . Cusw. canoer itn_ I(1~ ttis 

LT'2-xT1 

Is passive smoking an added risk factor for lung 

cancer In Chinese women? 

1-C, Koo' Ph .D . . J .H-C . Ho' M .D ., D .Sc ., F .R .C .P ., F .A .C .R ., 

D . Saw' F .R .C .P .A ., M .R .R .C . Path . 

6O".'rA%Mt N Co~iry M .liaw . U .lws+ry N Nons CAw4 N004 [wai 

s if . ~ N .D . lw.uiot N frdisCOtr 6%d Owrslofa. QwM tIisalah Narwl . NF a{ Crws 

s il. • N .D . l .a .uuu M Lh.t.a• Qwrn AisuaA Nrwul . Hw+[ KeRt 

XD f.ma2s btnt eranwr Paients .W =0 k..ltk7 Lhuitt .mtr .l4 w.v ircs~ 

.itwed to ilsaiU7 snd euantJfr tl. r.rious aure. .I p.u .. seeokieq . ...ng 

Chinas (emil . la Hong Koeg . F« tl+s evervmokas- p .ui .v se}osurs h.o 

wa-tal roure.. (id .a .pre .u t. add u ebe{r ri.k . F.. tJ. .e•era+e .Ys. 

,ualltaav . asaes.roenu (.n,olt Ga"urt euetvnr . ss. .Acn Fsui .e esptuee 

tur+rd) . and qu+ociuti .e s.an .manu (bours . rasm inretuir7) she . .l r s: 

Q+iresac ditfsnnco 1~sTw .en cbe tat . (or pci .nu .nd .onrrols . M.r•wvt . 

Loes t .lscirt eti.W vut sto( rxtiaisd .iih ikither leveL of pusi•e sewking 

for tLs r.a M s .c+mokvs . T)ius. svr ru,dinp .ould usea, to inliaate 

tbac Faui .t smo{uru, ss u+ i .otsied f.nor . lid .oi lu .s ae 1r+lluence .n 

(s=al . luni ancc isadsnss in Hona K. . .4 . 

Recently, there has besn renewed dierussion 

on the possibie etfeeu of passive 

ssmokins on 1un= eaacer risk (5, s, 19) . 

ta paviouw studies oa tht possibility of 

incrmsed risk of lung cancer among wives/husbar-ts 

trolr, tlleir smok ;af spou• 

ses, the dau (2 . 9, 12, 16) were on]y bssed 

en wbe :her the spouse smoked (yes/no) 

witth no funher quslifiutions on whether 

the smoker actua .lly staoked in the pre• 

seace of the subject and for bas+r loaQ . 

Whero t qusstifiation * was done (S, 

17, 1i), it was bued on the eurrent spou• 

se's smoking habits . lt !s weU known that 

the eaxcinoYeoetic process of iateraal solid 

csacers tuually begfns 20 or more yurs 

beiore di.agaosis wben there might luve 

besa no e.zposuss frorn the eurreat sour• 

ee . Funhe :more . little account was taken 

of et.anges ia stabking habits or marria . 

re, or'the possibility of exposure from the 

work eaviron:aeat. Some of tseu pto 

Rsewi+tid lacuwry 14, tM+ . 

• t. .bw e.pw .n Lr eevrian .iw.l/ Y . sru. 


blerns were raised by Harnmond a .nd St• 

likoff (11) but they have ytt to be ad• 

dressed by epidestiological srudie .s tA dtte . 

Chinese females in Hon= Kong hxve an 

averaè annust.i age•sund.ardized ineiden• 

ee rate of 24 .1/100A00 tor lung cancer 

(13) . This is aflong the highest rates for 

woraen in the world . In order to etore 

diroctly assess the possible role of passive 

smoking ia lung cs .acer development, a 

retrospective stvdy of 200 female lung 

ancer patienu and 200 healthy district 

controls wu brrua in 1911 . Hong Kong, 

wit.h an average urban density of 2'I,000 

inlubitinis per square kilometer, and I 

sa' of average livinf space per person. is 

one of the most densely populated atess 

1a tbe world. It is, tturefore, an apprsr 

priate place to test the passive smolcing 

aetioiopal bypothesis . 

P .rieats and -setbodi 

Tl+ )00 lusi sanest }scenes sy6i .d wae htaes 

tA. ." ir *u•s+aumc iausmseo @( t br .nuJs 

.., z .7~

p . .ive ssnoking e}sic is Ckinss w.msa' 

lad. In addidoo to ever-smokers (S), therc re staokin` at botae (H), workytaca (iN') . 

were xIlosr who lud eohabitins rslsuves or both (HW') bad X.Rs oaly mtrSinally 

asnokinY in their presence at home (H) . 

or tDosr da.i.)y exposed at tbeir workplau 

for a auraber of years (W) . In Fg . I three 

tn u.-seetin t cirtJ cs La v e b .ea dra wa to 

0kovra sevctt possibie catcj orics aad one a- s+'I'' ""*'*"' 

4ol .ited circle (N) representinj those who 

lu .d aever beea ezposed to any of thcse 

stIular aourtet . Passive erposure ls de~ 

aotez3 by the shaded area . and includes 

sidutrcam smoke hom lSOme or workplace 

To set wizether this qtulitativa method 

of usessmeat wou7d duc irninau higher 

risk Foups, all patienu and controls we• 

re fined into tac :, af these i d4fferent 

smoke exposure atejories and the odds 

ratios were caJculated (Table II) . It t8osr 

wiraing none (h1 represeot the standard 

witt a relative risk (RR) of 1-D0, smokers 

with no other source of ezposvre (S) or 

triu]tiple sources (SH, S' .' . 3HV,') had RR.s 

ranting from .2 .Sb to 5 .45, wheress nonamokers 

who were only esposed to pusi• 

Iva : saakad 

Passive axpoiure at vork place 

t4 1 • smult t+rrot,uV meso .ia . 


i 

T .kk II • Ralmiw tiio fRR! 1 .. AJJ.r++ . ersd.Jlr 

.ra*Mn 

o...... .. ..rn faau .a, i...sn r 

s a 

g u ~. 

1 ;u 

14 

SW 

~ 32 ~ AIt ' .Ri 

w. . .t a.o src 

s . s.us.rt,.~W,.s 

1 

1 : N 

s., . .a. .. ..rrr Nt..u e....1i a 

s•s:•sv .svs~ ty ~x s .xx• 

s-r .w u i, t .u• 

r u ar s .so 

' •SG .a.w, 

lassiv . •xposu :a ; ; hors 

i 

znti..: a.o s+a 

No exposuz• ca :aed

scm L .C. « ai . 

greater tharl 1•00 (tanjt 0 .l1•t3f), Whcn 

smokers aad tbosc oaly passivety ezposed 

were 57oupod (Table IIB), the 3tR of actire 

smokers was 323, and that tor the pas•• 

aive smokers a lioa-sipifinslt 114 . 

Quanrij`3coriorl of prusrve t++sakilsp 

CYu .r detailed lntcrvicws ailovred us to 

e3tirna.ie the amounu of pusive smoking 

from vsrious piacen in terau of boun or 

ycarY (Table III), Smokm as a group 

had more ezposure to passive smokinr 

from others thin the never•smokers . Dr 

pendinj on ahe ur,it of messure :nent, whe• 

ther hours or years, we tound that araong 

the smokers, the patieau had rnore hours 

of exposure . but the controls had more 

yex :-s . Amot:Q the aever•smokers, the con• 

trnis acalaay had more hours or years 

ihan tbe pltueau, but these differences 

were miai.ma:. Hours per yr.ir was used 

as a meuure of inuasity of passive eorpo 

aurz . Overall, there was to tizzinca .at 

dittcreacc in ezposurn levets bsc.veea patier,u 

and eontrols, whether t,hey wex 

smoke,-s or asver•smokers . 

Tsbit itj • Avt+eyr eesv+RU"na 'asaw wi+een 

mvkr srrosurr ry ri .cr, 

/1a,a 

3 .ar. 

p.+ rr• ps v ..T•rn 

11 

•rtL..u 

73 

~ .er.lt 

N 

petss, 

f1 

M .~r.L 

W, t1 .l7f i1 .711 U .1f1 u .77/ 

T.ar, It .f )t.l Z3 .7 L•3 

sz , ..+.aa. . 

/ .J77 t,Wr 2 .ttt l,Ml 

t.ar, , 3 .1 i .r e•• t . : 

SA . :ful Ywnu 

Me, 

t.a, 

a/ .711 

3•,1 

1:1 .1i! 

31 .• 

if .Ml 

ae, . 

ai .eli 

u,l 

awr+lr..r fff•/ 1t1•7 pT .O 1ti .t 

Since about 9011 of the tota .W aatounu 

of passive srrlokins car»e from the home . 

Table IV ahows the average eontriputian 

from each whabitinj relative who amokod 

!n the presence of the szabject• Ouly diretl 

tzposure was coustud. Husbaslds who 

amoked, but s4Sd tu+t ssxpose their wiru 

to passive smokiag for .uious tsssoas, 

aucb as tivfaf ovezseu, on mvellisiE }obs, 

etc ., wese llot included irl t!x sstimatiotu . 

From the C2iinese culttlral practice of ha• 

viag extended famS]y mcmbsrs living to 

getber, the fetma]c could bc exposed to 

her partau' cirsrettes or pipe whtn younj, 

to her busband's and in•laws' tobacto du• 

ring marital lfte, and to her children's ci• 

rarcttes when old . Atthouth in terms of 

hours/pcrson, parenu wert found to be 

a heavy source of sidestrearr, smoke, only 

a minority of patienu or eontrols wert 

to exposed• The most frcquent source was 

that rrom the husband_ 

About 2/3 of the toul hours of tobae• 

to ezposurc were calculated from our 

dau to be from the husband's cirarettes . 

hoth cues and controls had ar averagc 

of about 20•000 houn of passive sxrsoicuig 

trom theis homes . to that to signii,cant 

ditfercncr in exposure levels waa fotsnd 

betwes:, them . 

TaIz IV • jwo•cY .r P.m .ti srrouet a 400" , 

Iwtye •na: 4nr .,, 

LA3 pes*u t" wenL 

r • ewr,i• ., .r . r a+ ..,ip.., . ., 

a ..e.. 3v U .ul tu 3• .Ilt 

U 

, 

il .!•a tl 

s 

:1,76A 

1, :17 

A11in,. 

' LaduleJ wro SI srrin .u wt !I rwc»4 ruti• 

.w 'am''e arpos+r. I f RM7 

290 


• 11•nl 

la 

U 

4,si1 

: S 11,t7/ p,/t2

Unlike the Louisianx ttudy (n, we 

fotmd tso asscciation of aa tncrsa.st to 

disk of ltl: g cascrr amonQ currcat amokess, 

su .tmokcri . or neveramoksrs and 

euterira or pateraa .l (yca/oo) amojda= 

Wilu. 

,pn.oftsnt tdstory a+a kistotojy 

AtnoAj the sver•staorers, thsre wu a 

prcdotataance of aquamous aDd ezaall al) 

types od It,lns tumoun, .+bereas the opposiu 

pattern of a predomiaa.nce ot adr 

ao:.ar-.iaoa~u was fouad for those passi• 

vtly erposed and the N eateYory (Table 

V) . There was no tipificar,t diiference 

ts1 etll rype dismbution betweea the pas• 

tively expoatd womea and those with no 

relr.llar orposure . The predornitunce of 

ade .nocarcinam:s in the aever•sraoked 

womea u atroup, rt=ardless of tAeir 

passive smoking history, has been rspor• 

acd sisewbere (I, 4 . 10), 

? .iY V . srw+"ns Miaa•t ..r .l.r.+etr 

s..s.{ Warr7 

l.il r7}t 

frw. .r. • ....r .. .uw • 

aril (r11 Lrp L.11 

9-wt MrM NS (11H7) l/t (3+/tJ) 

l"+t•" a~uo Ai1 CU/7f) 3n (i6lit) 

ar* i71 ( 7/tf) I71 l17/1f) 

Rirk smon j xever•rnokerr 

We have easlier :hown that the averaRe 

total amouzt of bours or years of pu :ive 

tasokla= among the . never•smoken wa, 

stot signif•ica .atly dlffereat berwrea patirnu 

and controls . Wc also did not l5s1d 

a hiiher 3LR amonj patients with passive 

sxposure levels of > 35,000 hours (3 botus 

12 ttsin ./diy s 30 years) than thou with 

lower ezpotures (Table VI) . 


Hwhs emokis~g tuk h Chir,a. . v.e+tn? 

TJk V1 . RR N 1wy Nwrn w+R d rWV&0WAAen 

tt /rwli .l rww .eWar 

ft-"n Na,at sMn.l . a r +1M 

n 

!9 

s~ 

Y LM 

{/w, 

tt l.il t1 . 

~t 

s~. .~ f .. .~ .. 

t+ 

k 

11 

11 

1 .13 

t .1 . 

OI .M 

t . . .# 

t tsj= rat 

> Isl+CO /n..z 

It tt poutble that the lsr0sehial CIIu• 

enaa is more rusceptibie to casrino ;osu 

before adulthood tlla.n later ln lite . Table 

V71 sumtmarized our data on a .gs when 

pusive ex-+osuse t;tarted for the euver• 

ataokers . There was no siLnifiea .nt -stiffe• 

re.ace b

KAo LGscai. 

kta= oaaoer . To s+e if psuivs smokizg 

.dds risk to active smokers, the risks for 

4ht smokcrs (< 100 k ; tobacco or 14 

µtk rrs .rs) witb low or sto passive ezpossum 

(< 13,000 hours or 13 bouss/dsy a 

3C nars) asd tbose smokin: sdmllar 

amaus:u but witb bsavy passive smoke 

scposures were compared Cfabie YIII) . 

The same eomparison was applied also to 

the besvy amokers (> 100 kg or 14 pack 

?ears) . We found aot only ao iacsrase but 

aa acYtul desrease it the risk for botb 

ifgitt aad heavy emokers rritb heavy passive 

ezposurs eompatrd to tbose with ao 

or 1ow expdsure. There was oa]y an (ncreafe 

in the risk related to the kvels of tbeir 

own ciruetu consumption . This result 

was also found by Correa at LL(3) . 

7tb4 vt11 • RX M r .wk ." .iIV wJ .•ubw 

ru„w erewar . . 

~7t+ htass. wer.L IL 

t :: `+s-~'^ 

. . :, .."r.". ~ . M 

uac ~.+.., .. ., 

i5 .> rra.r11 .ta N 1~ 7 .4i 

Sa. 07 so w+suti 

W~TY K[k 

~Mnt , 

a.w tu u 

iJOt?ts .".cnv '>la7tI ri.nro 

' t tlAOO wown ' t tl1q0 howl 

Disctinsioa 

Ia t2t9s retrospettive study on the pos• 

sible influence of passive ststoking on the 

high iacidence of lung taaeer it Hong 

Kong Chinese feaules, we have attempted 

to identiS;+ and quantify various sources 

and typa'of tobacco exposure among 200 

patieats and 204 district controls . We have 

Umited our dau prsseztation to show oaly 

those facton r=levatt to the ittue of 

passive smoklbt . AA more deu3led descripiSon 

andn disctusion of active smokint as 

212 


a risk factar was presented alsewbere (is) . 

The appareat lack of aa as :ociuton 

betweea pascfvt smoking aad the " of 

lun; nacer in our study may be due to 

possIbilitiss whlcb ocruz because passive 

amokinj msy be ody t ary Mrah esrri• 

Dozen, whose affect may be coaosaled by 

ot2ter factors that play a role fa a melti• 

factorial and multisuge ardoloty. Among 

the femaJe aeYSr•uaoksrs, lnts•rvaaint 

factors mi=bt eause an ovessludowirit or 

a protective effett (e{ . brnachial irrita• 

t(on, dictary s ot betacamuae) 

. These factors fn Hong Kaad are li• 

kely to be ditfereat from those fn Japan 

(12) . USA. (9, 16), or Grerce (17, 1f), and 

this differr.ace may ezpiain our different 

sesults . The possibiliry that the ; dose•re• 

spatue cusve resembies a lotistic it shs• 

pe . such that c there is a dose greater 

than srra which produces zero rrspoase • 

wu r•onsidered by Hasnmond and 5eii• 

koff (11) and may be opiratits= bere . 

Cen.isJy the lack of an iacrosed risk 

for the active smoke :-s from passive tmokiag 

. whicli was also found by Corrsa ct 

ai . tS) . Would aex .= to support the poesibility 

that the effecu of active smokLzg 

or, tadeed, otlser taotars ytt to be iden• 

eifled F=17y overshadowed ehc art ;ino• 

èaic acuon of passive sMoking . 

This, however, does eot iirtply that passive 

smoking is iabocuous, as It may con• 

tr;bute an added risk of other respiratory, 

and cardiovascular diseases (i, 14, 16) . 

The possibility of other factors like diet, 

previous Eistory of respiratory diseases, 

occupationsl wtpostues, ase of istAalaau, 

etc .• overshadovving or inhibiting the ef• 

facts of passive smoking on the risk of 

lung cancer among aever•smoked females 

in Hong Kong and also the roles of these 

factors in the arcinogenesis an beint 

investigated. 

It is hoped that more direct assessmestt 

of passive smoking by other wor• 

ksrs !n other areu ean shed atore light 

oa the passive smoking eoatraversy .

1 

AM..4adM..ww 

1Y. r4h s ssr.r am j* .doad . .d *a.b r YK 

lW3ir'{t{ VGOBCCO6! Wtl "ridtY11 fK Aft1 (Mfl 

` Ali/ }fB/om am HM1/ r.N{ AJ/4r•JiEYf 66CtT7 . 

a .d tLs losaxh .+d Gcfercnc. GMtl C.ftaaa.r 

.r tlK M .d;na7 r.aAe7 K•"Amb crvu Awe .+ 

4110 Usi .aruh' .! H.nt lC.ut f.r fi.a+dal wrtwrc: 

hd .ror CJC Mok. Dn . MX. {ac. KX. La . M .7 

w .i, v .C. Ckait. L Hou. tx tiw . C .w . Ckac 

id X.T . Tiua ad t'iur 1[. Asuinr Mr dtir 

.d•.is rd 1 .* 1tlr . C- Cir Ma . C . T.nt ..1 

1i4. N, i.n f.r Ldt 1. Lu dl .criao .d au)7- 

,it : r1 Ma . 0 . Lsn. Mta. T . Lr ad Hi A. 

Chow f« .asu,isl w1tw.« 

Rdtrssm.. 

l . Ch&n W .C . Ca)knan: M .1 . Funj S .C. Wo H . 

C- Imncdial mnter is Hon! Krn! 1f7b1117 . 

Ir. I . Cu,car, 3!: It2•!!2, 1979 . 

i pua W .C_ F=8 s.C_ Lvu rncn r re, 

eook .rr ie Honj Koag la. Gnismnann L. Itd .) . 

Catxa Camotitn . Voi . 7 . Cuetr toidemiolorY . 

trunjtrt/Nr. Y.rk: Gmru• F'ucAa V.rtaj . tl+. 

241 . tit2. 

l. Man w .C . M .cLeaaata L : Lia nr+cer M 

Noat fCont Cau,.u .orulirt a+e kiiMtopu) 

tT" . tKStl12 . k . 1 . Catsa . ~! : ?212~) . 

1f7l . 

• . Caotrr D .A . Cnru AJt.. >iwroc KA: h+• 

a .ry .Ucsaa . K de iamj i. ranr,otas. 

AreL In .iroe. Hni,A. 16 ; 3K4C0 . 1944 . 

f. Corr. F_ Picrle LiV . F.n"m 1L 1.ta Y . 

H.maal W . : Fuai .t seoY,iaj .ed hmj oanosr . 

Lans+s, Y : lf5Sl7• 1943, 

IL Don It., H)ll AA. Km" L : T1r rjnirr 

OtHCt hr ttu C/1rt {! R1ltion ID Mt rRi6)ofY 

.f ks+t •an=• tr . ( . G+rosr . Ii : il+t, am 

T . Do11 L. Frm R.: T1r r .u.. . .t .ncsr, tuair 

rt.uve .emur .f .aiLall. " rf sriea 

M *A Umied iur.o w.7 . I . Nu . Gac . taw_ 

i1 : 11i'1•)SOl, 1141 . 


tsaivs t:aokiaW dkk ir Cklaw aasa? 

i. LdiaxiaL• hrivn tioktas: hersL Grf -d 

fibca . Lmsm k l4LS4f . 1oi2 . 

f . Garilnkd L Tbm uusd+ h Iri r+rr 6or 

WJr7 arosl Yoo-moktrf atrW iMtt • MO . 

jir. .eoklnt . I . Hac r...wr 1 .w ~f : !a,• 

eau . tos1 . 

ttf. Gmw I1, irntr7 t : Cr.h ... .f db iraj 

M .oatmotnj C2,ur. ...m 1vst . ( . itK .. 

134 ; !!)•31+ . 1142 . 

11 . Hiric...e LC_ f.tlko(t Lt . ltiriv. .mrr

e 

w 


, 

Iru . J Cancer: 39, 1ti2-169 (1987) ~. . P 

0 1987 Alan R . L.iss, Inc . 

MEASUREMENTS OF PASSIVE SMOKING AND ESTIMATES OF LUNG CANCER 

RISK AMONG NON-SMOKING CHINESE FEMALES 

Litsda C . Koot, John H-C . Ho~, Daisy SA'w3 and Ching-yet Hot 

il3ept of Communitv Medicirte, Univrrsirl of Ho+tg Kn+t ; . Hong Kong : 2Radiwhtrapy Drpr ., 6aprisr Hospiral, Kowloon, 

fa'ong Kong : and 3/ruriswe of Parholog) . Qurrn Efi ;ehrrh Hosptrcl, 14jlir Road, Kowloon . Hong Kong . 

. 

. 

. 

t.Hetime e :powrss to enviro~nm.ntat tobacco smoke from 28 .t}00 inhabitir,ts/km2, with tmly 

the home ac workptaci for tY "rsever-smoked" ferrule lung a{uce per person . 

eancer patienu and 137 "t+ev.rsrnoked " district contr-alt were 

S m2 of available living 

•stimated in Hong Kong to a .ueu the possibie causal rotationship 

of passive ,mokint to lung tincer risk . llelat}.e risks 

MATERlAL AlJll MET1fUDS 

based on the husband's unokint habits, or lifetime estimatas 

of total yean, total hours, maan hoursiday, or totsl ciraraest 

day unok .d by aach houuhold smoker did not show dosa 

rsponse rawta . Similarly, when such catetories as mean 

hours.~day, or earlier age of inicial eapowra, were combined 

with Ygan of expoture, there were no apparent Increases in 

From 1981-3, E8 never-smoked female lung cancer patients 

and 137 never-smoked female district controls were interviewed 

as pan of a larger retrospective study of femalc lung 

cancer in Hong Kong covering 200 cases :nd 200 controls In 

the orig nal study . pauents were matched with an equal numbtr 

relative risk . However, when the data were sepe=ated by of healthy controls by age (f S years), district of residence 

histological type and location of the primary tumor, it was (N-34), and housing type (pubGc or private housing), the 

asen t.hat peripheral tumon in the middle or bwer bbes, or, laner being in indication of soc)o-economic status Det3ils of 

fess strongly, squamous or smalt-cell tumors In the middle or 

}ower tob*s, had incrsuint ratauve ritkt that might lndicate 

some assotiatlon with pauive srt .ohin= eaposure . 

subject selection, lung cancer histological typing, and method 

of conducting the interviews have been discussed elsewhere 

(Koo et al ., 1983, 198A) . Never-srrwked subjects wrre defintxl 

as those who had smokeA less than 20 cigarenes ip the pasi . 

Epidemiologieal dsu linking passive smoking %kith lung All dau on ~assive smoking exposures were double-checked 

cancer among non-smokers have been controversial Six studies 

(Htnyama, 1981 ; Trichopouios ei al„ 1981 ; Correa ci al ., 

1983 ; Knoth et al ., 1983 ; Miller, 1984 ; Garfinkel ri at ., 1985) 

found significantty elevated relative risks (RR) in the range of 

2 .0 to 3 .5 based on the smoking tubits of the spouse . Five 

other studies (Garfsnkel, 1981 ; Kabat and Wynder, 1984, Chan 

and Fung, 1982 ; Koo ei af ., 1984 ; Wu cr al . 1985) two of 

which were conducted in Hong Kong, did not find significantly 

elevated RR from inhalation of sidestream tobacco smoke 

Four of these epidemiological studies (Hinyama, 1981 . Trichopoulos 

er al ., 1981 ; Garfinkel, 1981 ; Chan and Fung, 

1982) defsned exposure solely by two questions : whether the 

spouse smoked (yestno), and the number of cigarenes smnked 

per day by the spouse . Five other studies (Correa er a1 ., 1983, 

irSiller, 1984 ; Garfinkel ei ol., 1985, Ksbat and Wynder, 1984 ; 

Wu er a1 ., 1985) aJso included questions about whether involuntary 

smoke exposure hnd occurred at work (yes/no), and/or 

whether the parents has smoked (yes/no) . Such data seem 

rather crude indices of exposure, providing only very indirect 

iaforrnafion on tbe 6KTrer add amount of exposurc . Funher• 

morc, altrtough spcntse(s), parents, or co-workers might have 

smoked, the actual degrte of contact of the non-smoker with 

tttese smokers could have been very low, or even nil (Friedsrun 

ei a1 ., 1983) . In our detailed sasdies (Koo ei at., 1983, 

1984) of passive smoking exposures, smoking parents or 

spauses were sometimes rocalled as inflicting litnle or no exposure 

on the sub}'ut . In those cases where, for example, tfu 

husbard smoked but lived aepuated from the wife, then our 

study counted such wives as unexposed subjeru . Among our 

never-smoked subjects, this was found to be true for 3 cases 

a.ad 3 controls . 

In order to asseu the possible qusal relationship of passive 

smoking to lung eancer risk, dau from detailed life-hisrory 

exposures ttut were elicited in intensive 1 .5- to 2-hr taperncordad 

interviews of never-smoked female lung cancer cases 

and district controls havc been ana)yxed . Emphasis is placed 

on the eonsistetscy of the data, the strengths of tltc RR, and 

whether dose-tccponse relationships were present . 

with other data elicited in the ltfe-history interviews, espeeially 

residential pancrns since birth (i,ewhere she) liver :, 

type of housing . number of rooms, number of eo-habitants, 

etc ), occupatloru, and rnanul life to reduce errors in estitnating, 

exposure levels 

Among the txver-smoked subjects, the mean age of the 

patients was 57 .8 (so 10 .81) and that for the controls was 59 .3 

(sD 9 .94) This umple included 60 who were widows usd 3 

who had never mi .rried ; eone had rrtarried more ihan txsct . 

In the design of the interviews, separate data were eallectad 

to take into account that within the life-histories of the subjecu, 

sidestream tobarcro smoke could originate from : (a) 

different people who stnoked in the presence of the subjest ; 

(b) different places frequenud by the subject ; and (c) different 

types of tobacco . Persons who smoked included related and 

unrelated members of the household, and even co-habituns 

who shared an apartrrtent unit (if their tobacco smoke was 

tooticxd b) the subjea) . It was difficult to quantify expoi ;ilre 

levels from places that could have varying daily amounts of 

environmental tobacco smoke and were occasiorully visistti 

by the subject such as cinemu, while playing majong, or in 

t7anspon vthicles . This analysis will ottly take into account 

exposures that remained relatively regular during the lifetttnes 

of the subjects i .e . from exposures r.l borne and the workplace(s) 

. Among our subjects, tobacco srrsoke mosdv otiS'saued 

from cigarettes smoked by household members, ared 

from pipes (water and regular) smoked by parents or in-laws 

In addition to data based on the husband's smoking habits, 

4 other measurements of passive smoking were evaluated : (a) 

Ioul ycars ot exposure, (b) total hours of exposure, (c) mun 

hours/day of exposure, and (d) total cigarettes per day snwked 

by each htwsehold member weighed by their years of exposure 

. These rrxasures should be a more accurate ref)ecuott t~ 

past lifetime expasures than simple ques :ions based on whtthc,r~ 

the spouse or pesenu sawked (yes/no), or whether envitvrt~ 

menul tobacco Ismoke was encatntered in the workplace (yen 

no) 

'ihis srudy of thc effects of passive smoking is panicularly 

pettinent to Hong Kong because n is one of the most crowded . ~ 

urban ettvironrnents in the world . Its urban dertsity avetases Recoivad Jux. 24, t4a6 tad in ycvised fotm Sryternbar 19, t9iG la-A 

~ 

~ 

~

.;.:~: . ~.. :..,.x 

f.t_LSrvE StAGK.rNG rN CHINESE FEfdA1 .FS 

The toul years of exposure were derived from adding the 

years during which tobacco exposure occurred in the home or 

workplace . Exposures of 6 or more months were rounded off 

to the next year ln the home environment, household smokers 

were ottly counted if the subject necalle.d that they had smoked 

in herptc sencc, Where exposure was concurrent, as in the 

ase of xtxxh parents smoking . or exposure occurring at the 

home usd workplacc, then the years were no+ added 

The tota] hours of exposure were calculated by multiplying 

the average hours/day of exposure by the yean of exposure 

from each househoJd smoker, or thc amoum of exposure u 

each workplLce . Each of these sources of expausrc wu t}xn 

added together for each subject The hours were not added for 

exposure to simultsneous smokers, For eumplc, a husband 

and son smoking at the same time for 1 hr would only be 

counted as 1 hr . 

The mean hours/day of exposure were derived by adding 

thc hours/day of home and workplace exposures and dividing 

this figure by the age of the subject . This figure approximates 

the average number of hours of exposure per dzy experienced 

by the subject, spread over her lifetime . 

A weighted average of the toul cigarenes per day smoked 

by each household member was ealculated from the summa• 

tion of the usual number of cigarenes smoked throughout the 

day by each household member muhiplied by the years that 

each lived with the subject, divided by the total years during 

which eiguene exposure had occutTed in the home This 

figure rnal give a better tndication of the intensity of cigarette 

exposure tn the borrx than one simply based on the number of 

cigarenes smoked per day by the husband, becaus.e it accounts 

for other household smokers and the years that the subject was 

exposed to each smoker . This figure excluded exposure from 

pipe smoking and the cigarene consumption levels of coworkers 

be.c.ausc of difficulties in quantifying tbosc amounts . 

Of the 86 patients, 83 were typed histologically . Among the 

remaining 5 usrs, biopsy or cytologic materials revealed that 

maJignant cells were present, but they were too undtfferentia• 

ted or unspecified for categorizuion by cell type Chest radlo- 

U phs were examined for all cases, and the site of the prinury 

g tuRror was classified by iu location in the bronchial tree, 

and whe2her it was centrally or peripherally siruated, In this 

analysis, the IingUla was classified ascq uivalent to the middle 

lobe, and peripheral tumors were defined as those located 

beyond the segmental bronchus . 

Sutistiul analyses included the calculation of RR as the 

crude or adjusted odds ratio and tests for trend (Breslow and 

Day, 1980) . Adjusted odds ratios were euirtuted by the tue of 

a conditional logistic regression package, PECAN, (Lubin, 

1981) which was based on N :M matching by strata defined by 

district (N- 34) and housine type (public or private) . To take 

into account the effects of potential confounders which affected 

the Rk estimates, adjustments were made for age (

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F,ouR€ I- Measurementu for passive smok)ng lfnd RR for lung ancer 

'Adjusted for Rge, number of !(~c b(nhs . cchool nF (*/-) and 

years since exposure to ciEarmc :moke wsxd in the t,omc or workplace 

p C 0,05, 

PASS7VE T).1O1(.JNC (N airNESE FEM/.LES 

the squamous or small-celf lung tvmon than anwng the adenocarcinoma 

or large-cell types (Table Vl) . This was especlatly 

tsve for the adjusted RR in the former g•roup, as 3 of the 

4 measurcmen(s consiuently indlcated irscreasing risk with 

increasing ezposure . 

lvcvrian by lobe 

Eighty of the cases had the rnain tumor residing in one of 

Ehe lobes The remaining 8 cases, with primary turran in the 

right or lefi main bronchus, or in the rlght intermedius region, 

were too few for analysis . Calculations of the F:R rhowed that 

none of the crude or adjusted values were signifuxnt for 

upper-lobc tumon (Table Vll) . For the middle or lower lobes, 

all of the adjusted RR were in the comparatively higher range 

of 1 .9-3 .5 for those with some passive ezposure~ t~ .lorr,over, 

for 3 of the exposure mcasurcments, toul years, hours/diy, 

and cig.renes/day, the confidence intervals for the cnsdc and 

adjusted RR indicated some borderline cignificant values . 

However, none of the trend aruJyses for the lobe dau cunc 

out significant . 

TAILE Vt - MEASVREMENTS Of TASSivE SMOYJNG AND RR FOR LVr+G CANCER )Y }05TOL .OGICAL TYTE 

NWmisr o( eue" 

rumecro( 

«x.rdr 

L,u.mo.. .r rnahcen Adcruc ecrcwt, sr Yr}.~ll 

Rl('ttl! C() 

ItII'rflS Ctl 

Nre'en ef u.ei/ 

vmtcr d 

eo .rol, 

RA'r157 Cll Rl~~ RSt t71 

Toul yurs 

0 

1-26 

7/40 

10,46 

1 .00 

1 .24 t0.37, 5 ao1 

1 .00 

1 .58 (0 .37 . 6 77) 

12/40 

17/46 

1 .00 

2,11 (0 S4, 3 .74) 

1 .00 

2 .07 (0 .64 . 6,71) 

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) 

Toul hours 

(in hundreds) 

0 

1-150 

15) * 

7/40 

12/56 

13/41 

1 .00 

1 .22 (0 .34, 4 .71) 

1 .81 (0 .52 . 6 .54) 

1 .00 

1,40 (0 .34 . 5 n) 

2 .04 (0 .53, 7 .i;5) 

12/40 

1g/56 

16/41 

1 .00 

1 .07 (0 4E . 3 .05) 

1 .30 (0 .59 . 4 .02) 

1 .00 

1 .70 (0 .55, 5 .20) 

1 .57 (0 .55, 4 49) 

HoursJ day 

0 7/40 1 .00 1 .00 12/40 1 .00 1 .00 

f 

166 

PltlSimpllp[ripriCrtll ioCYNIOIr 

KOOETAL, 

Among the 85 determinable ca.ses, 46 had peripheral rumors, 

and 39 proxirru1 tvmors . Ah}augh only the crude RR 

of 2 .00 and adjusted RR of 3 .52 (or 1-19 cigurnu/day were 

slightly signif3cant for the proxinul rumors, in general . all of 

the crude and adjusted RR for the pcnpheral wmors were 

"ter than 1 .00 rl'able Vlll) . 

Hisrolog ;cn! typt and location 

In order to see whether any particular combination of histological 

rype, lobe, or proximalrperiphenl loution of the ru• 

trwr would result in stronger dose-responsc patterns by the 4 

lifetime measurcments of passive smoking RR were analyr.ed 

for the 12 possible l .l combinations . We were unable to 

segregate the cases into any frner ategories than 2 of the 3 

groups because of the small resulting number of cases for 

analysis Space does not allow tu to present all the ubles, but 

the best combination was that of peripheral tumors in the 

middle or lower lobes (iable IX) . Among the RR, significant 

or nearly significant figures werr found for the crude or 

adjusted RR relating to at least one of the exposure utegories 

for each rype of ineasurement, Moreover, the adjusted RR 

tended to range between the relatively high values of 6 .5 to 

18,7 for thosc with some exposure (Fig 2), and most of these 

were significant or nearly signiGcant . None of the trend tests 

came out significant, but this and the tendency for the higher 

levels of exposure to have lower RR than the low levels of 

exposure may have been due tD the small number of cases 

(Nw24) . 

Akhough not as apparent, squamous and small-cell lung 

cancers in the middle or lower lobes (Fig 3) also seemed to 

show some positive association with passive smoking There 

were only Ig cases with this type for analysis and none of the 

RR or tests for trend were found to be sutistically si~ndicant 

. Yet it wu promising to su that all the RR with 

(Table X) 


sonu exposure were greater than 1 .0 . Among the highest 

exposure levels for the adjusted R .R, values as high as 7 .0 

were found for totzJ hours, and 6 .2 for hours/day . 

DtsGU SStON 

For comparative purposes, tht rtwne comrrwnly used mu• 

surernenu of passive smoking based on yes/no tlttestions of 

whether household co-habitants (husband, childhood/aefulthood, 

or others) had smoked, or on the number of cigarrnes 

the husband smoked per day, were pn :sented . Only the crude 

RR of 2 .37 (95 Te C1 :1 .03-5 .91) for husbands smoking 1-10 

cigareues/day was of borderline si=rtifrwtct and txme of the 

adjusted odds ntios were signifscant at the 45% probability 

level . Thers was liale indication that increasing kvels of such 

exposure led to increased RR . 

On the basis of our extensive life-history data, we were able 

to calculate the total years, hours, rrsean hours/day, and cigareucs/day 

to which the subjects had been exposed tn tabacco 

Imoke a1 home or u work . Our esuimates were based on the 

tanderstarsding that the household composition of each subject 

would change as she progressed through the life-cycle of birth, 

childhood, adulthood, marriage, nwtherhood and, for 27%, 

widowhood . We also included exposures from each workplace 

at which the subject had worked for at least 3 months . In our 

adjusted RR, the eficet of cessation of exposure to passive 

amoking was accounted for by ptming in the years that expoture 

had ceased at home and/or workplace as a corttinuotu 

ncgreuor variable . 

Despite such dctailed aocouruing, we wert unable to find a 

sigru fiunt trend in the ensde or adjusted RR for tixse 4 

9ifuifrre moasuremcnrs of passive amoking . Althoug3t the RR 

for the imcrmediate level exposures of hours/day and cija- 

sY 

It .Oo 

12 .0 

6 .60 

4 . 00 

2 .00 

t .oo 

0 

. 

Nont LoM 

Exposur . Lrv .is 

High 

Total ysars 

Totat hourr 

tiourslnay 

Ci9 /day 

Frouee 2- Measurements of passive tmoking and RR for periphen : 

lung earscen in the mddle or lower lobes, A,djusted odds rauo, 

Y w 

! 

9 .00 . 

6 .00 

5 .00 

I 

: 

S 

r 3 . 60 

3 .®0 

1 .00 

Mon. • Low 

Exposura L.v .ls 

High 

Ftauat 3- Meuursments of passive smoting and RR for squamau 

and amall-oell lung ancer in the middle or lower lobes . Adltwnd odds 

eatio . 

N 

rettes/day were signifrcant, e}x RR at the highest levels of ~ 

exposure for these two variables fell to a non•significant 1 .0• ~ 

1 .2 . In fact, the RR for the highest exposurc levels for 3 out f-M 

of the 4 measurerrxnts were below all of those with lower 

expowru, ard ranged from a very weak 1 .0 to 1 .4 . On the ~ 

other hand, etaoxt of the crude and adjusttd RR were jreatrr 

ilun 1 .00 . 

11 "1 

CA 

~

fASSIVE SMOKING IN C'11)NESE FEMALES 167 

TAILE VI11 - MEASUREME"l7S Of PASSIVE SwOK1NG AND tR FOt LI~NG CANCFJt !Y LOCATION OF TVMOR 

hnp/Ynl 

Wn1ar M crr,' 

e..r~c, e( roe .ra, RR' eri71 Cli RR~ (151 Cfi N-0cr d 

ar~w,rr r1 cav w, 

heasr+sl 

(1SI Ci) . . . R!


168 KpOETAl . 

Measurements based on increuing intensity of exposure, 

defined as increasing years (or hours, or cipretus/day) by 

mesn hours/day of exposun, also did not indicate a doseresponse 

relationship Likewise, the analysis of toul years of 

exposure with age of exposure did not suggest ehat arlier age 

of initial exposure and increasing years of exposure led to 

higher RR . it wu troubling to find stut in both rypes of 

analysis, the RR for the lowest amounts of exposure were 

among the highest values . 

Dalhamn et al . (1968) noted from their study of the retention 

of cigarette smoke components in human lung, that waterinsoluble 

volatile compounds and particulate maner from eigarenes 

tended to be deposited primarily in the deeper parts of 

the respiratory tret, Sina aderwcarcmorru is predominant 

among non-smoker lung cancer cases (59% of our typed cases) 

and it is tencrYlly a peripheral tumor, we wanted to see 

whether the passive smoking measurements would exhibit a 

more consistent pattern among the adenocarcinorna and largeall 

types, and/or among the peripheral tumors . In general, 

the pcripheral tumors as a group showed stronger dose-response 

results than the adenoearcinomu . • 

The RR for total years, hours, and hours/day measurements 

of squamous and snull-cell lung tumors indicated consistently 

elevated risks with increasing exposure . This panern was not 

found (or an) of the adjusted RR for adenocarcinorna or largeeell 

lung cancers . This association of histology with passive 

smoking is also suggested from previous studies by Trichopoulos 

er al . (1981) and Correa er al . (1983), 

Analysis of the cases by the lobe location of the tumor was 

done to sce whether the primary tumor resided more frequently 

in the upper lobes than in the lower lobes . This is 

because it is known that when dust is inhaled, it first enters 

the upper lobes where much of it is deposited . and then travels 

down to the lower lobes (Time, 1980) Furthermore, it has 

been observed (J .H-C . Ho, personal observation) that up to 

half of the Hong Kong adult population have radiologically 

evident scars on the upper lobes of their lungs Most of these 

scars are due to previous tuberculosis infection Since "lung 

ancer is more common in the scarred and chrontcally diseued 

lung" (Stone er al ., 1978), we were interested to see whether 

the lobe data would subsuntiate any of these possibilitiesln 

fact, 37 of the lung ancers were found in the upper lobes, and 

43 in the middle or lower lobes . The results from the RR 

estimates from the 4 types of ineuuremenu did noa show the 

upper lobu to be more scnsitive to eavironmental tobacco 

smoke . 

Wynder and Goodman (1983) suggested that lun u»cer in 

non-smokerslvu more likely to occur in the periptery of the 

lung . This wu found in our smdy, as 54 % of the determinable 

cases had peripheral tumors vs . 46% with proximal tumors . 

Moreover, the pattern of RR with die various rneuurements 

of passive smoking indicated that peripheral tumors seemed to 

exhibit better dose-response RR than proximal tumors . 

14'hen the RR were alculasod for die 12 pouibk 1 :1 canbinations 

resulting from histological type, location by lobe, e+t 

proximalp /periplseral txsmon, the hifheu RR were found for 

pen tKral tumort in the rniddk or bwer lobes . Signifieant 

adjusted RR as hith as 1E .7 wett fouad for some of shese 

measurements . Att~ough RR at die bwer doses tendod to be 

higher dun tfut for the hig3ser doses, the dau were consistent 

Yt that all the RR for ttwse with some exposure were much 

~rca ter tt~an 1 .0, and the adjusted RR for at least one of the 

itR fot erchtype of ineasurement .ras ttuistially significant 

or ocarly sitnt'frcanc, 

7tx RR analysis for aquunous and small-cell 1ung cancers 

in the middle or lower lobes also appeared somewhat better 

ttun the others, with tocal hours and hours/day muzuremenu 

alsowing some dose-responu panern . With the above two 

combined analyses showing some promise, perhaps the best 

RR would have been obtained if analysis had been done with 

squamous or small-cell peripheral tumors in the middle or 

lower lobes . We were unable to do tl>ese calculations because 

only 8 cases fined into this ategory . 

Actually, the finding of a possible risk of squamous and 

Kmall-eell tumors in the middle or lower lobes was somewhat 

unexpected, given that dust particles tend to adhere to the 

upper lobes, and tuberculosis usually affects the upper lobcs . 

To see whether calcified foci or fibrosis in the upper lobes 

could account for the higher RR in the middle or lower lobes 

because the previous presence of such lesions might disturb 

the expected distribution of inhaled particulate or gaseous 

matter, most of the chest radiographs of cases with squamous 

and small-cell lung tumors were re-txamined . No significant 

difference was found in the proportion of positive cases with 

upper lobe vs . lower lobc tumors . 

In out analysis of all never-smoked cases, the lack of a doseresponse 

pattern, and an almost consistent drop in the RR at 

the highest doses of exposure would seem to lend linle, or 

only weak support for the passive smoking linkage with lung 

cancer for women in Hong Kong This might be due to the 

facr that it has been estimated (Rylander er al ., 1963) that the 

non-smoker exposed to environmenul tobacco smoke receives 

about 1% of the active smoker's dose of tobacco smoke based 

on coatnine levels in the body, and this is toughly equivalent 

to the tobacco smoke of 0 .1-1 .0 cigarene inhaled by art active 

smoker in a day . Moreover, a 15- to 17-year longitudinal study 

of 97 non-smoking females in Holland did not find an usociation 

between passive smoking exposure and pulrrionary function 

decline (Brunckreef er al ., 1985) . Thus the effects of 

passive smoking might be so weak that they are easily overshadowed 

by other environmental factors such as diet or exposure 

to inhaled gaseous/paniculate rnaner from other sourtrs 

in the home or the workplace . 

When the lung tumors were segregated by histological rype 

and location, the resulting analyses showed that peripheral 

tumors in the middle or lower lobes, and squamous or smill• 

eell tumors in the same lobes, exhibited better RR parurns foi 

passive smoking in terms of consistency, strength, arxi dose• 

response . We are not sure whether this proclivity for passive . 

smoking-relat.od lung tumon to reside in the middle or lowei 

lobes might be due to the fact that the lower lobes have morc 

bronchial cells at risk than the upper lobes, or whether the 

size, weight, or composition of gaseous or particulate manet 

from passive smoking may favor its adherence to die periph• 

eral areas and the lower lobes . Nevertheless, the overall proportion 

of lung tumors in the middle or lower lobes among oui 

88 cases ranged from 27% for the peripheral turnors to 209E 

for the squamous or small-cell tumon . Thus, the rrujoriry o . 

lung cancers among our non-srnoking population were proba~ 

bly due to some factor(s) which yet remam to be identified, 

The results from this uudy, showing a weak effect of passive 

amoking on the risk of lung cancer among never-smoked Hong 

Kon~ Chinese women, must be interpreted autiously, since i 

was based on only d8 cases and 137 controls . With this umplc 

size, RR less than approximately 1 .4 would be difficult u 

detect with 95% power and at the 5% level of signiflance 

This problem was even greater when the cases were suatifKc 

by histological type and location of the primary tumor . How 

ever, these data seem consisunt with the findings from othe 

epidemiological, biochemical, and physiological audies i• 

showing higher risks for squamous-eell eumors in the peripF~ ~ 

eral areas of the lung . Confirm>Uon of these findings fror, , 

other studies is therefore needed . ~ 

ACKNOWLEDGEMENTS 

Cz 

We tfunk the Hong Kong Anti-Canoer Society and the Un 

versiry of Hong Kong for financial auisunce in the carryin 

601 

OA 

CA 

0;1A 

C4

MSSIVE SMCW,ING IN CHiHEESE hEMAlES 169 

pn of the fieldwork . Wc are also irsdebted to the US Natiorul the dau The ucrcurial usisluKt of Mrs . T. Lun, Ms . A . 

Ctncer Institute's Folury lnternatlonal Center for sponsoring Chow and Ms M . Chi, and the graphics work of the MedicaJ 

a 4-month Visiting Scientist post in the Epidemiology and lllustration Unit, arc gratefully uknowkdged . 

B,tosuds•tics ProYnm, which was invaluable in the ana3ysis of 

E+ttsur.' . N .E ., and DAY, N .E ., S+a+inirol rwrihodi iw owcrr rouorrA, 

IARC Scimcific Pubbaaia+ 32, IARC, Lyon (1990) 

®tu+EUaEEr, B ., Ftsn+Ex, P ., REwur., B ., Va . pEa Lcxt[ . R ., Sewou 

TEt., 1 ., and Qu .wEa, P ., indoor aur pollution .nd iu cf(cn on pulrtarurr 

}ynetion of arJult aon-smokinS women ID Pissive vrolun3 md Pulmosnt) 

funcYionJa J . Epidem , 14, 227-230 (1925) 

RFFE1tENC'ES 

QuN, W.C ., and Furw, S .C„ L+mI anccr m .on•smokcn io Honl 

Kanl M, E Grundnw+n (ed,) . Cancer camperjn, Vol 6, Canc-rr eplde• 

a:olol(y, pP . 199•202, G Fuchcr, SaraSsn, Neu York (1912) 

Coa>tit, R ., Retem~on of ciprette 

croke eomponenu in twnun IunYs Arch en,iron Nlrh„ 11, 746-748 

l t9d8 ) 

Fu¢+.+A,w, G .D ., PtTTm, DB . . and B .WoL , R .D . Prcvdcncc .nd Cor• 

teLtex of ptuive smokme Amer . J publ. N6h , 73, 401 405 (1983) 

6ARnwrJ .u, L ., Time uends in lunj cancer mortality .rtwnf t+onsmoken 

snd b nae on pusivc trtwkine I fta Cnncrr lur , 46, I061 • 1066 (1981) 

GAitstractl ., L ., Atrouux, 0 . . and 1otnEaT• L ., Involunury imok nI 

and )un3 eancer ; a case-control swdy . J . Pat Cancer lnrr ., 75, 4b3-469 

(1915), 

Htc.tY .MA., T., Non-smo)un8 Wfvea of heavy srnoken have !a hiElxr risk 

d lunj wtcer : i stud) from Jqun . Srtt, rnrd J., 2i.2, 1S3•1t5 (1961) 

k,uAT, G .C., and r/YrmER, E .L. . La.= arcer m wn-unokers 

Cancer, 53 . 1214-1221 (198A) . 

K .+trrx, A . . BoH,, H and SewHrr~r, F . • Pusrvnucfien .IS LunFcnkrebs• 

~esr~che bei Nschu~..uchennaen . Yed . k6n . Pra: ., 71, 5a-59 (1983), 


Koo, L,C ., Ho, J,H-C ., and L[E• N ., As aealysis of wme risk faaon 

for Luas cancer in Honj Kong hv . J Cencn, 35, 149-135 (19t5) 

Koo . L .C . . Ho . 1 .H-C ., and S ..., D ., Acvvc ard pusive tmokin; aman4 

krrxle bns cancer p .tienu and eorttrots u Hon= KonS JI cyeLn 

Caurr Ret ., 4, 367•375 (19i3) . 

Koo, L.C ., Ho, J .H-C ., and SAM, D ., l+ pusive mtoicinl an aided risk 

L.ctor (or km3 amr in C'htnae rvoeten'' J. eq . du C.nc,rr Ret., 3, 

2T7•213 (1994) 

Lua+w,1 .H , A eomputer for the an.lysis of smclsed ere ooaad 

rtudtes ud t e s Consp d,a+ned s ., 41, 13i•143 (19Y1), 

Mn.t.Ea, G .H ., Cancer,pu sive smokin~ md .oa«nployw aad emp(oyed, 

wt .cs Wrn . J Aled, 110, 632d35 (1914) . 

RYUwoc. . R ., trrusor. . Y ., and Srr¢uJ. . M{•, (c'd ) . E7S-EnNron• 

•.erua! uboecn rwsote Atar, C•~ersev . (1963), 

S1,HOtEK . D,P ., Wucoz, AJ ., and Evt3ao«i, R .E ., Cumulative effecu 

of lifeume pauive anokJn3 on nrtcar risk Lancet, 1, 312-315 (19E5) . 

SToN[ . D .1 . GLucK, M C ., and PAucH . N .K„ Pranical Poirus in pu(twonan 

diuaut, p 125, Modsca) E . .rnv~•iio„ Publsslung CDntpany, New 

York (1976) 

TIwE, ArJa of rAe body, p 59, Rand MeNally . Chicaj*o (1950) . 

T>ucHOrout.os, D ., KALAHwot . A ., Sn.nRos, L., and M.cMk»ou, D ., 

Lun3 aricer vid pISsIK un0(C]ng Mr. J. C.ncrr, 27, 1 .4 (1911) , 

Wu, A .H, HermEnsoti, B E ., tucE, M C ., and Yu, M .C ., SmorinS ard 

ot)ter nsk (.non for Ja+u euKSr in woarn . J . wt. C..ncrr htrr„ 74, 747- 

751 (19fI5) . 

Wrwnuc, E .L ., and GoooMAn, 1.t T ., SrtsoklnE and lun; nnaeT~ aotne 

anreaolved i .sues Ep,drm .. P" ., ; . 17';-207 (1983) ,


9

Lee, P .N ., Chamberlain, J ., and Alderson, M .R ., "Relationship of 

Passive Smoking to Risk of Lung Cancer and Other Smoki .ng-Associated 

Diseases," British Journal of Cancer 54 : 97-105, 1986 . 

exposure in the workplace and nonsmoker lung cancer was published in 1986 

Another European study including an assessment of ETS 

. The authors wrote that "overall the results showed no 

evidence of an effect of passive smoking on lung cancer incidence 

among lifelong nonsmokers," although they presented no odds ratios 

for workplace exposure . The following point estimates have been 

presented by one of the authors of this study in a recent book : 

for females, 0 .63 (95% CI 0 .17-2 .33) and for males, 1 .61 (95o CI 

0 .39-6 .60) . 


;.~.;,,. . .. _ . . _ _ 

it, J C,,,rr. (t y0) . ,bl, }7'!OS 

Relationship of passive smoking to risk of iung cancer and 

other smoking-associated diseases 

P .N . Lrt,` J• Chambrrlain & M .R . Aldersonf 

bssrrrHrr oj Csncrr RcuorcA, Chjton Road. icG*o++r . Surrsy . UK . 

S. .ry la t*e lasrr r+an of a(arjc kcnr .ul ps>< .oontrol ∎udy .f al1C #ciuYCnship of trl+c of aastctu 

rnoked so nYi 01 v.noux sewol nj•assavtod d-sc2ses . patoents an+ .rrv6 tiuca+wnt rsn tk .molsnj kaF∎tt ut 

tJanr first ly+o..e and on shc sannt of pysure s+nokt tayosun at Ao+ne . at rork . slunnY sravsl an.d dunnp 

kcwrc In an e:tenuon ef t!w uudy an .ttempt vu a,ade to oburn raokt+nj Aab .t dau Euutlr trorn the 

apouses ot all Mfebnt non•tmokint lung onocr wa and ol tvo Netonf Ron-smoktnl matehed eaatrols for 

uch auc The attempi .ac nudc reprdles of .scthcr the ptienu iad ansrcrad p .u++c trnolurg rirauaru 

iws hosput or .ot 

At•aonpt tifetonj ao*-uno4M . pan+K sn+oking .a3 aot anoclatad .'nh an7 trMrxiat i11c1WG tn ntit o( 

kmt arssr, ehronrc bror,chuu, atclucmrc hcan duux or urotc rn any analrus 

L+miutiom o( put suud,-s on pass~" smoltnt arc dunusad and t!x a .ed for (utther ea~earsh rr+dcrttncd 

Fron+ all the ar.,Lb1e r+denax . tt appc.in that any efT.n of dan, .e arnote on etsl o( any of th¢ asa)or 

9ueara that 1as bocn asu%vtod with an~-c amoAtnZ u at sncst smalL and au> >+ot sa .u at aJl 

Srudy ojAospire/ n-portrnts 

In 1977 a largc hospital easecontro! .vas initiated 

to study the rctattoruhtp of the type of taprstu 

smoked to ruk or lun ; eanaet• ehrontc bronehitss, 

ischaemic hean disease and strokc This sttxiy was 

orried out in IO hospital rt :rrons in E.ngland ; 

intcrvretitn4 tnded in lanuary 19112 , The ongtnai 

qurst+onnatrc did not includc questions on paisive 

fmolcinj as tt -as "t considcrrd an unpontant 

Itsue in 1977 . However, in 1979 it was de+nded to 

txtend Ihe questronnaire lo eovrr paut+•c smoktnj 

for rrurned patrcnu for lhc tast four ricrons to 

begin intervmnng Subsequent(y, in 1961, follown4 

publtcation o( the papen by Htrayama (19E1) and 

by Trichopoulos er o1. (1911) elatmtn j, tha t nonsmoking 

wt .ts of tmokers had a s+jnifieantty 

greater risk of lung rancsr than non-srnoktng .wes 

of non-smokert, it .as dectded to iiricreau the 

dumbcr of inacrvirws of numed lung anoer nses 

and eontrolt The ectended qtxsuonnrtre was then 

administersd to ahex patienu in all hospttats rhere 

iatcrncwtnj wI.s uill conunutnj 

lydllo+r-srp stsdt• O/spustl s/rtrsrs-t+r+rs[+R{ Aatpiral 

aii-prsrnu 


(n t9t2. sfter intervieWing of Aospiul in-p.tieats 

had barn eompletod . it was dmdcd to prry out a 

fo1loW .up atudr . !n this uudy . an attcmpt taas 

Cornt{wn,der,tt, P .N tac 

7roeat lyddnas 25 Goar Aaa4 Swsoe, S .arrty . SsA .? 

f1yG . 

tM4nsene addr .a Olfiae rif !•oqulauoa Censsaast .nd 

Zur.ers. ft Cat4r.c's Hot.e . lo Kiapway . LowQon 

w1:2{ slp . 

snade to intrrview the spouscs of all of the numcd 

hospital ip-pauents with lung t.unaer who rcported 

ftrer hivtnt smoked . as well as of two marricd 

non .smokinj controls for och of thcsc indc>< lung 

ancer ases The foliow•up study wYs intended 

paniy to sompare inforrnatron on spousa' smoking 

kubits obtaincd fsrst•inartd with that oblaimxf 

axond•hsnd dunnd ahc in-gutirnt intcrivicws . and 

partly to ssbtain somc dnta on aq .ours' amoktnL 

ksbu for thosc pa .cnu who had wot anac.Krcd 

pauivc smoking quations u+ Isospttat . 

This papcr ennocrttracts aolcly on the iuuc or 

prsuvt smoking in litelong non•smokeri Giaults 

relating to typc o1 dgarrttc smoked arc deuritscd 

ehewhert (Alderson rr a1 ., t9iS) . whtbe a cletaikd 

+rport, arailabk on "uest from PN(., eonsiders 

Ux orsrall findtnrs from thu sueronarol uudy . 

!r1 rtt,otEs a r1 rts'ewt 

Stwly of hosritot aa-ratirarts 

For act, of lhc 4 is+dca diagr>oazs (lun& canc .ohronlc 

t•ronchitis, iachat:mtc inn diseasc ar_ 

strolc), the intsation was to inurview a00 casrs 

usd 200 ntsatrhod controls in tach oC tbe Rtrht 

aat/age mlls (i .c . mak o( kmak. tusd aged ]~ 

45-~4, SS-64 or iT-74), 'fhis ;ave a tarret of 

12.t00 petxnts, though fs» sone atcfonss te .U 

young femak ehronst Woncftitses) this rrould be 

tuutuinabk . huenu werrc wiactsd from aredksl 

(tsdudioj ch:st taedsdine). Usorseic turrcry, and 

tadiotAcrapy .ards . Conuoh Wene paticnu without 

•ese of iht four i+rdcx diagnaaes, iadivsdually 

toatcfisd b seses oe tca, a,fe ., boxti;Htal neYion ar.d, 

0 71c /s4,c,nittan h:oa t.td , 1"6 

I

1st f N LE F a .r 

when possibk, hospital ward and tsme of sntrrr»cw . 

SuMtpu•.ntly, whcn final discharge dtaFnoscs 

txs.arrx avatlahk . thcy were used to rcalloute asts 

and controls as s+eersvry Patients without a finxl 

diagncx_is keT+t thcir (xovrstonal draFnosts Where 

chanEcs m casctontrol sratus oaurrrd, paticnts 

were rcgroufrd intn nrw osetontrol pairs as 

appropriate With the asststancr of Sir Rschard 

Doll s+r,d Mr Rw•h,,rd Petu, non-tndcs duEnoses 

werc classtficd as follows 

ciass tA 'definitely not smoking associated' 

clau 18 'probably not smoking associated' 

class 2A 'prob+bly smoking assoaated' 

class 2B 'dcfnttely smoking assactsted' 

Controls with no final diaFnosts were considered 

class tB Ovcrall, thcrc were 12,693 intcrviews 

carried out which srsulted in 4 .950 pairs with class 

I controls and 73P patrs with class 2 controls . 

Ttyer : wcrc 3 .g3 : interviews of marrtcd cases and 

controls whcrc the passive smoking qucstionnaire 

was completed In order to avoid substantial bu of 

data, duc to one mcmbcr of a pair rsot being 

marrscd or not compkttnE thc pauivc smoking 

qucstionnairr„ it .as decidcd to ignore matching 

when anatysinj thc pauire smoking data and to 

comparc cach rndca sroup with the combir>ed 

controls Numhcrs by acs and asccontrol status 

•re riven in Tablc 1 . 

Tab1e I Numhers c/ msrmd twspital in-patsents 

ownt+tct nt p.u,ve amol:mj rJuesttonaatrn 

Mat. fe.rk Ta+at 

Lunt canat $47 245 792 

t'hronK broechttu 182 N 266 

(sehaemK Mean dtsease 216 221 !0'f 

Stroke 161 137 2!1 

Contvok 

Clas, tA and 1!1' 8)9 713 1J52 

Lhasr. 2A and 2!S` 2" 149 417 

Total 2.213 1549 U32 

'Othcr dnc.asos .rtrs dauift.d by dclFnc a( asokins 

wocutrcro - dass IA rkfiatsety wot, dass 1t MobOWy 

tol, das 2A prohably, dan 2! 6cfrrutely 

In the pass+vc amo .rns prrt ol the questionnaire, 

patients wrn: asked whcn the aurrute siart .d, if 

and when it had andod ; the lumber of 

osanufactured ciprtttes per day smoked by the 

spuuse both during the last 12 months of aurtiaè 

asud also at the period of maaimum smoking during 

the nlamaje, and whether the spouse oMer ttYutarly 

smoked hand-rolled eiprettes, dprs Gr a pipe 

during the marriatc For amnnd or subsGquent 

tsarruga, queuwru related to the Gru anarria=c to 


give the IonEcst taunt snterval bctwecn exposure 

and dtseasc onset The S+attcnu wert also asked to 

quanttfy, acxord+ng to a four•potnt acak > ;a lot, 

average . a kttk, not at all), the extent to which they 

were reEularly esposed to tobacco smoke from 

othcr rcoplc fxior to comtnF tnto hospital in 4 

ssituations at horne, at work ; dunng daily travel, 

dunng ktsure tisrse, In the main qsses .tionnain, 

dutaik-d qucsttons wcrc askcd on smoking habits 

and on a whole ranFe of possibk confoundtng 

variabbes 

Follo .-srr Nsd) of Jpousas of raon-smoli+sX looaptrel 

An-patwnts 

From the hospital study thcre were 56 lung tan=r 

qws who reponcd being hfclong non-smotien, 

who werc marncd at the time of intervier and who 

were not known to have bccn married previously 

In a follov.•up to the main study, an attempt was 

made to intcrvxw the spouses of thcse $b cases and 

also ihe spouses of two hfe-lont non-smokine 

controls for tach ase, indtviduxlly matched for ses, 

tvuntal status and 10-ycar arc group and, as far as 

possibl ., hospital Where multtpk potential cAntrols 

in the same hospital wcrt available, thoac 

intervicwcd warest in time to the case were 

selected Whcre suitablc controls in the samc 

hospital were not a~ailabk, thoss in the nearest 

Isosptul werc ehoun 

because names and addresses of the patients were 

ssot recorded in the hospital study, st was neacssar) 

to to back to the hosp,tal both to obtain this 

information arid also to get pcrmtsston to intervxu 

their spouses FollowinS some nefusaVs both by the 

iwsprtal and by the tpousrs . sucrosful intervsews 

were obtatrsed from spouses of 3 ; cases (10 wives 

and 24 husbands) and 90 controls (26 wives and 5A 

Musbands) whosc condition was definitely or 

probably not related to smoking 

Intcrvsewinf was carried out between July 19$2 

and August 1913 The spouses were asked about 

their eonsumrtson of manufactured cigarettes, 

t:iFars and pif+cs (a) rsowadays, (b) dunng the year 

of admrssion of the patient or (c) maximum durinf 

the whok of the rnarrsagc The spouses wKrs oot 

asked about the smoktng hatwts of the i+rdes 

prtsent The sf+ouus wne also ∎sked questiont on 

sEe, oerufutson, aoetal elass and a range or othcr 

potential confounding factors . 

Starisrirol awraAods 

The statistical methods ars kused on eiassiesl 

proocdures (or analysis ot Srouped data derived 

frorn nse-eontrol studies (Breslow & Day, 1980) 

In Senenl, the material Aat been etumincd as a 

2 x K x S tubk, with A' rcj+rescnting the levels of the

isk factoc of Interast and S the rsumbcr of ttrata 

uscd to takc axount of fsotcntral confoundcrs 

Results ptcxntcd arc for the combined strata and 

sho~ the rclatu .c nsl. (Manrcl-Harnszel esumate) 

to=ethcr with the siFntf~canac of its drfTcrence from 

a basc kvel (nil 1 0), and or the dnsc-rclatcd trend 

In analyses ~of the data cnliectcd in fsot(ntal, 

comransons arc made hctMccn oscs wtth e 

panicular indcx dncasc and all the controls with 

drsoscs dcCsnrtc(y or probably nnt related to 

smoktnp Srs umpic indrocs o( pas%ive smokc 

e>trr nses 

and 112 matched controls rho refsoned nrver 


M^,~ •Y+` .Mw 

tASSIYI: iNOKING AND ssdoKtNC-..RL( .ATCr) niSFASfS a, 

having smokcd in thcir hosryrtal intcrview Of tlvcsc, 

therc ercrc 47 casa (IS mak and 32 (cmalc) and % 

controls (30 rnak and 66 (cm.k) for a+,,om sortx 

information on srnokrnF habits of thesr srnuscs was 

availabk Of those 14] pausnts, information on 

"usc smnktnE was availahlc hcsth from the slxsusc 

and from the paticnt for 59 (41•h), from the s(soucc 

only for 55 ( .1lS! ;) and from the patrcnt onl) fur 29 

(20%) Table 11 slwws Ihc estrrnatcd apc•ad)usrcd 

retativc nsk of lung nncer in relation to a{xw%c 

smoking durint the vshok of tlu marnaFc, by act, 

source of dau, and f+enod of smokinF None of the 

9 relative risks shown in the uhk are statr%trcalls 

si¢nifrnnt, Whtn daln for hK+th seses and both 

sources arc twnudcred, thc rurmatcd ro(rtrvc nsks 

in relatton to spousc arnokrnF arc closr tn I(1 .11) 

For individual Caa or fouracs, whLtc numhcn of 

saxs and controls arc amalkr, rclauve risks vary 

morc from rmity, but sa consistcnt pattern is 

tvident S+milar oonclusions wrn rcached . when 

analyses wsrc based on smoking durinb the pcar of 

kaapital intcrview Herc, the overall n :latrvc risk 

was again cbsc to 1(0 93 with limits 0 41-2A9) 

Tabk III wmrnariscs concordancc bctwcen 

spousc's rrunufacturod agamtc smokrnR habits as 

rcponed directly and indirectly for the 59 (,atrents 

with dau from both sourcrs b,scrc7wncres were 

uen for 9 sfsouscs (IS! :) in rrsfsect or smnkrnF at 

sAmc time durin ; crsarruFc and in the rrsc of 2 

T .We 11 Rttsru+n .hir bnacn apovst'r wunufactur.d o[3t0S0-)4r1 

L+rl .e wur .rx.-s .J rAr nlri Iwww n bsrud (M pusnu+) 

Mak 7 IS 5 7 133(0 17-6 -Lt) 

Femak 9 17 1 70 6 7510 24 .2 40l 

Camb+ned It 32 1) 21 IQCNOEI-2 

Iastl .r, /utr awncn .f q/ar>warba . (!I) p.rrerwsl" 

Nak 7 It. i M IJO(O .LCJ .rI 

Ftrnak t0 21 22 45 IAOt0 .)1-2T1) 

Combn.ed 17 37 - 30 !1 1 .1110,51-2 .1'91 

"Jwty owstras twcsud .d rn (otb. .,lp .rdi tuaoecnd, %ta ttws a.atysu urc 

apousr .as aounted as a rnoker if repon .d to Ic ao atLer dlr.csty, y thc tposrse 

Iurinl (ollo .-up batcrvie., t,r, :drr.esty, by the palient ia Aogital Nae tlut tAe 

S1 ptrcn9s bt wbom iators .asion . . sposrc arnokin5 ..as availabk Ilrtna boah 

srwren are mduded in all ) aaalyser.

s .n rN t_rrr, .r 


T.Mr III Cnnnxdancc hrt .rrcn stu+u :'t manulactvrcd a}arctt< sw+nttnE latrts as rcpivirted 

itracyll and Md,r .nly 

S. : ./ps,~ru/ra.sr nwrr .f rrtu 

Ma4 fn .dr 

Ctsn C.wr .ti Ca.rs C .wwr .ls Ti.e! 

St+ousr a sm.+kn scxnctmx rn 

lnarrutr Itlt'++dutl H+ 

iubject and srovu 2 6 S 13 26 

Only wh)eO I 0 0 3 4 

Only spousc I 1 3 0 S 

Nathcr 3 It 1 1 24 

; sub)ect!spousc aFrerment 71% ttt% b7;, tt;, t5'i; 

Spouse a snrolrr during ycar or 

htrsp,ial tntcrru+ ao:ordtns to 

Luhjco and spouse I 6 2 4 1 3 

Only subjcct 0 0 O 1 ! 

Only $tx+usc 1 0 O 0 1 

I+o .thc, S ty 7 ~ 

% suhXct/sPa+sc aErecmcnt {t' ; t

s 

a 

a 

M.SSIVE SMOKING ANll SMUKING•Rf.L1.TF.D DISr.ASES Ht 

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• 

.m,•lrrs luandardi .c .f k,r as< and, lot t{.ourc ur+ollnL .IsctYsci sAt ssurrurr .a . onpwnt 04 ewdall 

- 

Iasslrr .wnlr F(alr wvats ie .a.lr prwus S+an rr .sMwd 

e :p,surr - - 

rslrc/1r+r! C." C."rrr4r 

r 

R C .v, Cw-+rnlr R CRVS Crwrrsls R 

At Iwmc 

Not at all • 101 1 21 112 1 3+0 293 1 

Ltttk 2 21 122 6 0 092 1 66 0" 

AseraEva lot 1 I I 1 I I 5 61 0t1 • 72 Olk+ 

At wotl 

Not at ail 3 410 I 12 113 1 IS 151 1 

Ls,tk 6 29 3 .24 3 21h 1 I% 9 55 112 

Avcral:c'a lot 1 29 0466 0 t1 00 I a7 019 

. Dunn f travcl 

Not at all 1 101 1 211 2 31t 1 36 3" 1 

Ltttk 3 16 206 2 SI 033 5 61 06A 

ArcraFe'a lot 0 13 000 0 13 000 0 26 0 00 

T rrnd 

jt+etatl .cl 

Ic005 

: 

. 

f 

Dunn1 klsvrc 

Not at all 3 45 1 15 116 1 13 161 1 

Urtk 

AverrFc'& tot 

4 

5 

16 

3'" 

1 12 

3 16 

11 

2 

107 

95 

1 05 

01! 

Trcnd 

11 

7 

155 

134 

1 .06 

059 

CombinC4 /r1de1• 

~ 

IKK1lIK) 

I',: 005 

Scorc 0-1 1 2~ 1 10 .?5 1 11 102 1 

Scors 2-J 7 35 13,4 S 61 063 12 116 lDd I 

fcors S-12 2 IS 320 0 21 0D0 2 36 050 

S(+ousc tmoled man ofs In Last 12 months 

No 10 105 1 20 19? 1 30 2.91 1 

Ya 2 2'9 0 % 11 122 076 13 151 079 

Spoust smoktd man oEs in rhok or atnaSc 

No 7 93 1 13 119 1 20 182 1 

Yn S 40 2 47 19 229 055 24 ?69 690 

•tuod on wm ol 0- wo1 at all . I . 4ttk . 2- asraEc . 3- a Iw tot at MOmc, at fMk, duruME 1prcl, durmE knuK 

asc"113-ice 

Over thc prst 1yurs thcrc has becn considcrablc 

rsuarch interest in the relattonship belwecn passive 

trnolrnF and risk of IunF eaneer in nonsmoken 

Whiic some studres havic elaimed a positlvY efktt 

(Hlrayama, 1991, 7nchohcwlos rr al ., 1911 . Cornci 

rr al„ 19R Garfinkel rr $l ., 1995, Giths rr .1. . 

1994 . Knoth trr •!, 19t1), othen (Suftkr rr sl . . 

1994 . Chan, 1982 . Garfinkel, 1951 ; Kabit and 

Wymdcr, 19it1, Koo rr a1, . 191r) kavc found tw 

tiFmft::n; risks of WnE 

nncer for nors-anokinE women srumed to vnokers 

wmparod to non-sawkinE .+omen Rsarried to aon• 

tmokers nnFe from wnurvhat over 2 in the 

1'r.chopoulos and Cortca studies to around O .')S in 


the burTlcr and Chan studies 7}u WeiEhte4 relative 

risk from theu Nudlcs ka bccn cstlmatad by us as 

approumalely 1 .3 . Whik there is, therefore, a 

t

la: r.N t.rrr+a+ 

yak~k V KCWuMl111p hctWt'tli 1wo MdKD or Ifaf .uK fTnIt c1rOSYTt and ntl 01 C:htOnK (KfNKhllt3, aKhit1711c •pn 

Ancarc and urolt amc+nE IJctont pon•snwlcn (atundardiw7 tot aFr and . tot is{oust tmokant. rAtllw tbc Irurrurc wat 

6ntnlnt ot srdadt 

raaurY sr-1r Mak'Irwlu3 le.rsJr rar.wti ,ftatt cwdwwel 

ti)W,arr 

./ .dri/lrlrl Ca.n C.rurrJi R Casn C.•urnlt R Caut C .+rrds R 

C/rnw/r IrwwrM'lit 

Cornbinal u4ct' 

Scott 0-I I 27 1 7 73 1 1 10Z 1 

Scorc 2-4 2 55 013 4 61 I05 6 116 100 

S,corc 5- 12 1 IS 110 1 21 1 .03 2 36 I10 

Sl+ousc unolal man cip rn .hok ol marnalrs 

No a 93 I 4 99 I 12 I{2 1 

Yes 1 -60 0.3+ 13 229 1 .22 ta 269 0.13 

LrAo~u lwan dvuv 

ComDbncd InJci' 

Scorc0- 1 15 21 1 2) 75 1 38 102 1 

5cort 2-4 12 55 01) 9 11 059 21 116 0.52 

Storc 5- 12 3 IS 04) A 21 Olll 7 36 0.61 

S(+Ouu smnlcd man np tn . hnk o( mamaFc 

Nu 26 93 1 22 19 1 4E 1t : I 

Yts 15 40 1 .24 55 229 093 70 269 1 .03 

S+rol r 

Comb"ncd rnSca• 

Scott 4 1 5 27 I 19 75 1 24 102 1 

Scott 2-4 10 15 f0 LI 096 20 116 091 

fcorc 5-12 ~ IS 177 7 21 2 W 11 36 2.11 

Spourt smoled man op In .Ac.h od marru~c 

No It 93 I ' 19 19 1 31 1t2 1 

Yes 1 40 0u 19 229 092 55 269 090 

'Oared on wm o/ 0- not al all, 1 . 4nk, 2- avsratc, )o a tot for at Aomc, at .or1, aunnt trartt, Iurnis kxsurc 

onc eapretlc would be 1I hours as tsEards 

panicuhlc mattct and SO hours as rctards nicotine . 

S+milarly, larvis et .1. (1965) havc Mown that the 

incrcasc in sahvary cotlninc in rctation so passive 

smoke cxfwsurc is kis than I'.4 of that in relation 

to activc amokc caf+osurc E :trapokatint hncarly 

from the t0-fold tclalwr rssk of king nncrr in 

lclalion to scllvc unoklnf would thcreforc predlct a 

cclative risk in rNation to rassive smoking kn than 

1 .1, while a quadratrc catrapotation, as tujlccted 

by Doll and Pcio (1979) would predict a lower risk 

aill . The contllct bctwrcn Ihc dou and the claimed 

raponse ia panicularly dear for the tasults ot 

Hirsyama (I"l) who found a aimitar efiact on 

lunj txncer ror passive anoking as fbr active 

smoking ot S ciprttla a day . 

5ccond, all the audia wffer from weak caposure 

data, most studia only obuinin3 infortnation on 

the tpowe's smoking habits and aonc obtaining 

obIoctivc data by measurement of ambicrlt Ilcveb of 

tnwkc oonstituents in thc air of the 6otrse or 


workplacr anG/or of concentrations of constituents 

in body rluids . 

Third, ao Nudrcs adcquately uke into account 

the possibility that misclassification of activc 

smokers as non•txnokers may 6avs oonsiuently 

biascd relative mk estimates ",ard Activl : 

amokcn havc a lugh rslative nisk of king ancrr 

and apouscs' smoking kabits are positively 

Oorretate•d fecausc of this, t1 can 6e shown tbat if a 

tclalively tmall prof+ortion of arnoken reny 

amokinE, this resuhs in an aploreal c"tion in 

risk of IunE pnar in 'aon•smokcri tnarricd lo 

amoken compared to ' .on•atwkm' nsarriad to 

aan-smokcrs, even when .o rsar sffon of pasaive 

smoking caists A dcmonuration that this aouroc or 

Was is of rcal Imporuncc can be found in the study 

of Garfinkel tt .! . (1985) Used on ttrlvalidated 

smoking data takcn from hospilal taoles, a rolative 

risk of lun3 nncxr in relation so Musb .nd's 

smoking at (some of 1 .06 was pkulated, with 

t'eiativc risks of at kast 13 aecn irs rclation to each 

:='-I 

_. . .. . . .~.,.~ ... .,~ . -....

t 

k 


kvcl or husband's oEarcttc smoking and in setation 

to huaharsd's ctFar and pipe smoktnt When 

addittonal sourvs of information on atnoking 

habtts were used . the overall rnlattvc risk was 

rc,duced to a marpnilly ugnif"nt 1-31 with an 

ekvatec3 risk onl) n:a1t) dtsrcrniblc in rcl:tion to 

fteavy cilare{sc smoktnE by thc husband Evcn itctt, 

it is sxwubk that the ckvauon in risk was t .ol 

evsdcnt when smoktng data were obtained from the 

subject or her spouse directly, but was only evidcnt 

when thc data werc obtatned from the dauShtrr or 

son or another informant, ir from those pcoplc 

who were icst Mkcll to have known the full 

amoktnF htstor) The (owcr rrtattvc risk may still 

have arisen wholl) or fsarsl) as a bas rt:suliinj 

from misctauiftcatton of smokrng habtts 

Founh, many of the studies are otxn to tp,xifsc 

eriticisms For elamptc . thc aonclus on of Gi11ts et 

•1 (1981) that male IunF cancer d~caths in aantmokers 

rose from 4 per 10 .000 in those not 

exposrd to pass vc smoke to 13 per 10,000 in those 

who wcrti esposcd was based on a toul of only b(!) 

deaths and was not tutisticali) silnificant . Also the 

claim by Knoth .r ./ (1983) of a tetationship 

between passive smoktnr and lung cancer in s>ton• 

unokint women was based simply oet the 

obscrvauon that the proportion of fcmak atontmokin= 

lung cancer patients ltvinE toFelher with a 

smoker escooded the proponion o( mak amoke :n as 

rcT+oned in the prcvtous microeensus . ignoring inrrr 

a4o lhc fact that in man) familics womcn I .ve with 

more than just their husbands 

In the preunt uudy no tiFnificant relationshir of 

passivc smoking to lung canccr incrdcnct in lifelonj 

t+on•smokcn was seen, either in the arsalyses based 

on the information collected in hospital or in 

sstbsequent inquiry of the "usn ot both It must 

be pointed out, Ao .ever, that the number of lung 

cancer pattcnu who had ncver smoked was rather 

small so that, though our findings are coasisacnt 

with p .uivc smoking hsvinE no effcet am lunS 

cancer risk at all, they do wot eadudc the 

poss;bility of a small incrcase in risk, tlsou=h the 

upper 955, sonfidena limit of 1 .50 for the awimate 

of 040 (Table IV) in relation to the .pousc 

smoking during the whole of thc marriage is nsot 

tonsistent with some of the brFer incraaw claimed 

by Hiraysma (19i1, 19N) Tric)wfroukoc tr d . 

(t9E1, 119113) and Correa rr al (I9d3) . 

Thoujh the numbcr of lunI catscer patients who 

lud rtevcr smoked a vrull, varying arowsd )4-50 

dcpendint on the analysis, this ntxrsbcr ic aot vsry 

different from that reported in a stm+ber ar other 

ttudies, e .E the fsndmfs of Corrta er atl . (19t3) 

.rere based on only 30, while thou of Triclsopoulos 

tt d. (1911) . even when apdated (Triclsoyoulot t/ 

a) .. I"1) srrc haed on only 77 . The difl1ruhy of 

obcaininj an adequate sample aix ie ..deriirsed 

.. .~.,.w. .s- , .,. ~.~ ------`-- .- 

rASSIVE SMOKING AND SMOKtNCrRtilJ17U) DIIUSLS N3 

when onc oowdcn that in our study the 44 acver 

arnoktng lung cancer paticnts who comrleted 

pauix smoking questionnairss in hospital were 

estracted from a tota( of 792 lung cancer patients 

It would srood a very Mrgc research efiori to 

irscroasr pracision aubsuntially, and even then onc 

would havc to take care that thc masnttudc of any 

biasa did aot csaeod the malnitudc of the effcct 

one was looktnr for . 

The two srulor prosfroctive ctudia which Rave 

so far reportod findtnFs on lussive amokin ; 

(Htrsyama, 1%1, t'iarfinkel, 19b1)' wero "t 

actually daiEncd to investiEatc this issue and, as a 

result, could only usc srousc's smoking as an tndct 

of eat+osure Out study, on the other hand, thouSh 

.ot abk to monitor eaposure objrcttvely, as would 

luve been prsferabk, was able to look at pauivs 

tmoktnj in a wider context, by asking about the 

extent of uposurs at home, at work, during travel 

arsd at kisun Although thc answers to tt•.ese 

questions were wbjoctivc, and could have eshibitad 

aome bias, their inclusion ptrFups allows `reater 

oonfidenoe in the oostclusions . 

It was interestint that, of the 59 patients for 

whom sqwusc's titarrttc smoking habits were 

obtained from both the sf+auu and the ptients, 

there were 9(IS!k) (satients for whom thcrc was 

dtsafr¢ement as to whether Ihc spouse had been a 

tanoker at torrse time during thc marrsafc . It acems 

rs:asonabk to suppose that some of thtse wert in 

fact svnokess and may have brrn erroneously 

dauificd as aon•unoken kad onl) one tourac of 

information been tr,cd It was also noteworthy that 

there was quite a strong corTClatton in our audy 

between actrvc and passive tmoktnF As illustrated 

in Tabk Vt, turrent smokers were considerably 

more kikely to be eat,oscd to yuive amoke 

cnpasure at home (from aourm other than their 

own ciE+rettes) thnn were t.ever or ea-smokers As 

sw,cd above, this corrcl.tion,' coupkd with some 

tnisclassification of smokers as st,on•unoken, tmay 

spursously intLte the estimate of risk related to 

passive smoking It is important to carry out 

fonher studies fo obtain more atxurate information 

on rtlublltty of statements about smoking habits 

benusc of this pocsibiltty of bus . 

Littk other evidence is availybk ebneensinf the 

rs:lationshif+ brtusen passive smoking sad risk of 

the other ta,okin=•assocsated dtseases in (adult) 

bon-mnoken and much of this is open to criticism 

(n kis original paper . Hiraysmn (19E1) presented 

tttativc risks of doth for various diseases for Ron• 

tMrwkinE women aacardinj to the Isusband's 

rwnokinj Isabur based on a total of 5b deaths, a 

dight positive trend tor emfshysema and asthma 

tras twt ttignificant, wfiik, based ou a total of 406 

•caths, uo indiation of a uend at i,n was aern for 

i.chaernic lrean disrase ta a Osttt paper, (xsad on

5 

tw f w k•Ef ff Y/ 

Ts4L Vt Rciatts ndd, at Aav+nE rs .uvc snwt,r npowrc rt Romc sowrd,n{ to 

/.atrent'> n.n x+.nu(anurc.f rtprettt smtdrng AaNts (standardtsed k+t ait last - 

~ comMned ci.s 1 and 2 cvntrtJst 

Rrtatrrr .f/% W', rnqfuirwr lswurs) 

Daw awlrpc hsl+a~ illalr jIA41r 

Ne .cr t 1 

Fs 125/n1k.1 Rit 11M4Rh tRt} 

Currcnt s .Oflf 2 67-5 fxt 2 51l l 74-3 62 1 

Ci .syuareJ k.r lrcnd t2df) 

r 

$1 .t 1 

Jrrds 

were current smokers Sandkr e+ a! (1985), in s 

czsC

l 


Rtf 

ALDI RSl1N, M R, LL1 . F N l M AN( ; R(iM~) Ra11 of 

lunX anm, ehrunK b+onchrtn, .ch .cmK hc .rt dracasc 

•nd strDle M eelatwn 1o lyi.c Of oK.arctta analw! J 

C~ Nlrh , 74, 2aa 

RRESIAM . N C S DAY, N E(IKO) Su/u/KS! A(rtM.ts M 

Cr..4r R-unrA I'.d I- T7.r Awal,W .J Cav-r .wr .d 

S+dwi InlcrYUtsonal ARrra7 (or Raorch on CAnccr, 

L>on 

RUFFLER . t A . MCKLE, L w' . MASON, TJ a CONTAI!'f . 

C(111a1 The ausn of tun( onon w+ Tc .u In lr+rt 

C.Wrr C..wr wsG frt.ewr .M, Muxll. M l Gxtn . 

P (edi) Vcr(al ChcmK InltiNlwnal InC 

Cf1AN, M'C (Rtt2) ZLhkn aw Honjlong .1li ..rA MrJ 

k' ..-A . 12IC 16 

CO#RLA, P . MCKLC . Lr'_ FO+.T/AM E . LIN . Y . a 

HACNS7.E.1.. M' (I11)) Pasu .e rewlsnE aRd lunt 

anacr L.+nt . Y, 595 

DOLL R a rLYO . R(147/) C.Farctu emolrnl aRd 

lptonchul aranoma Iou and Lmu reLsanahrps 

amonl rc/u(ar vnolcn and 4fcloni Ron•eewicn J . 

Ep&A'n+ C.wn Hfrh 13, 703 

GARFINKEL . L(1911) Tsnx lrs*sds in Wnj oket 

swruhty amonl non•vnolen and c Roie e+n pw .c 

Rnwlmg J N.rl C.rurm littu . M, 1061 

GARFFlNKEL L, AUERRACH . OA lOUDCRT, L(1"5) 

Invo)untary Rrnolinj and lunl onar A ar-0onlrol 

ttudy J Natl C.•rrn ltiu , iS, 46) 

GARLAND . C, RARRCR•C'ON'NOR E . tUAREZ L . 

CRIQUI, M H A wINGARD, DL (1915) EfraL of 

pauive Imolrnj on nchcmrc Ac.n dlscase nwrtahty or 

Ron•anolen Aprosf+ectrve Mldy Arwrr J . f,pfrM . 

121, 645 

GILLf3 C R . HOLE . DJ . HA%LTHORNL, V M t aiOYLE . P 

(19f.J) Thc eiiccr of environnxnul wbaoto rmoJ


10

Shimizu, H ., Morishita, M ., Mizuno, K ., Masuda, T ., Og-ura, Y ., 

Santo, M ., Nishimura, M ., Kunishima, K ., Karasawa, K ., Nishiwaki, 

K ., Yamamoto, M ., Hisamichi, S ., and Tominaga, S ., "A Case-Control 

Study of Lung Cancer in Nonsmoking Women," Tohoku Journal of 

Experimental Medicine 154 : 389-397, 1988 . 

Shimizu, et al ., reported that, in their case-control 

study of 90 women in Nagoya, Japan : 

Passive smoke exposure at work was not clearly 

associated with female lung cancer, although 

the relative risk was slightly elevated (RR = 

1 .2) . 

That reported relative risk was not statistically significant . 



rA1 

T~h,dcu J exp Mwl I :av+ 154 as', 1' 7 

A Case-Control Study of Lung Cancer 

in Nonsmoking Women 

HIROYC'K1 CHIM1ZL' . MCNEHIKO MORI5HITA,' K.ITSCI'L'kl 

111zC'r:o,t T.{KAo MASC'DA . : 1'l .•K1o OGCRA,: ailYSCHir :o 

SA`7TO,Z MINORC' `15Ht>1CRA .i KAZCO KC\ISSI>!A . 

KAZCO KARASAtt'A . KEtSC'KE "ISHIWAKI,V aIASAHI};0 

YAHAIJOTO .' vHIGERC HISA>ticHt aild SC'KETA?il 

ToxtNAC,t'• 

Drpart,nnrt of Public HraltL, Tohokli CHiucrttty School of 

.1lulicinr . Sr,ldai 980 . 'tht Second Ikpartment of Inttrnal 

.llrrflciur . \'nq~oyn City I'>rilvrsity, .llerficai School . Va•itht 

bw (fitle 171f .S . Code). 

S89 

~ 

NOTICE : M MATEAA11dAY dt MTECTCD 5Y ~ 

COPYti661 U4M` (T1Tt,E 17 U .S . COui .; ~ 

~ 

~ 

N 

~ 

~ 

i~


3fl0 H . 6himisu et .l . 

The causes of lung cancer in Japanese women have not been clearly 

identified . It is widely accepted that cigarette smoking is eaueally associated 

with lung cancer, but the increasing trend in the incidence of lung cancer in 

Japanese women cannot be explained by amoking alone . The proportion of 

smokers among Japanese women tamained around 15% during the last thirty 

years (TominAga 1982) and the most predominant histologic type of lung cancer 

among them n•as adenocarcinoma, which was considered to be more n-eakly 

associated with smoking as compared to lung aancer of other celJ types (Shimizu 

1983 : Takamurs et al . 1986 ; Shimizu et a] . 1986) . 

Several studies have been oonductcd with emphasis laid on paaaive smoking 

and lung cancer since the first positive results were presented by Hirayama (1981) 

and Trichopouloc et al . (1981) . Some of these studies showed a clear association 

of passive smoking with lung cancer (Correa et al . 1983 ;(3arfinkel et al . 1985 : 

Akiba et a) . 1986 . Inoue et al . 1986) . However, the resulte of other studies were 

, 

equivocal or negative (Garfinkel 1981 ; Kabat and Wynder 1984 ; Koo et al, 1984 

Wu et al, 1935 : Lee et al 1986) . 

This paper reports a casrcontrol study of lung cancer in Japanese nonsmok- 

ing a•omen, in which passive smoking and other factors such as occupational 

histon• . domestic heating system and dietary habits were investigated . 

MATIRIALS AYD MITHODS 

Our n~k> tronsistcd of female patienu with primary lung cancer who were treated in 4 

hospitals in Xato .ya from Au6ust 1962 to July 19&S . One of the bospitals (Aiehi Cancer 

Center Huspitall Fas a cancer boapiul and the eetaainins tbree were seneral boepttak 

V,tgoya is th, fourtC largest city in Japan .'itb a populauora of 2 .1 milleon and located in 

the nliddl~ of the mntn itland . Honshu 

During the rbot•e period 118 female lung cancer pati•enu ecere patbologically identifxd 

The ph .yiicun ; or nurscs uled all of them to fill in a qu .stionnaire for taia study on tbe first 

or second dat' of admt>sion to the hoapttals . Out of 118 lung cancer patients 4 refused to 

fill in the que>tionn .tire and 24 reported tdat they were current or enmol•ers . The nmatntng 

90 nonsmoktng pattenu were selected u the eaan for the following aael .ats . The 

questionnaire tnainl}• consisted of tbe questions about rmoking, oceupation .l history, 

dietan• hrbic :' personal disease hiatory and about the kinds of fuel for ooolcing. M rsEards 

passtt•e saaking we asl• .d them about the smoking habiu or the number of eiiarettes 

smoked per dar by p.renu, eiblirtgs, children or husband's parenu in the home . We also 

asked them about the length of time which the wonun spent with her husband in the same 

room, the period of married life and the number of eisareues smoked by her husband . The 

passive stuoke exposure at working placea .cu awseaasd only in terms of the prossnoe or 

absence of smokers . As regards dietary history, we asked the frequency in noent 6te years 

of intake of food items and dirid.d into four esss#ories (no intal-e, l or 2 days ; w .ek, 3 or 

4 days week and almost even• day) . We aaled directly the number of giaus of milk and 

the number of onutftec tal•en pet week . 

The 90 lung cancers included 69 .deaocarcinomaa (77y,), 13 spuamous eell c.reinomas 

(14°,.al . 4 large cell earcinomu (1a/,), 3 tma11 cell eareinoma (3°a) and I adenoid cystic 

ea.rcinoma (11,1 The number of e.w in the age poup of JO-39 . 4049, 50-59 . i4-69 . 70i9 

and t10-rears were 3(3° .), 16 (l7%) . 28 (31° .), 27 (30%) . li (16°,41) and 2(2° .a) 

tespertivelc The minimum and maximum " of the wes were 35 and 81 ysan and those

I 


Rt

392 


H Shimuu et al 

Tutt 2 . Mat= risib of lwnq canen ix aowswoks'rey 

vo--en ~6r sr.okinp by wothe+ sw1 kusbnad i 

latAe+ u W Ao.W 

&moLir>; by husband's father 

(-) (+) 

1 .0 

f .9• 

SmoL•ia6 by ootber (- 1 

(+) 6 .3 2 .8 

•p

t RuG Factors for Female Lung Cancer . 393 


TAtat[ 4 Relatire nsks fRR) of h.ng eanar in 

monsnsol'lny soornra for type of howeholri 

Araring sysu+n rxd tr nant yean 

Type of household Frequency in 

beating system controls (?o) 

RR 

Gu 32 1u 

Kerciae ne 66 1 .6 

Coal or cbarcoal 8 1" 

Tut.t5, Rrlatia risl•s fRR) of fu%q eonerr di nmvmolrNg ro~eN tR 

relation to tAe .elrted Joctors /n = 65) 

F .ctor 

RR 

Crude AdJuseedt 

Srmoking by tuother in the home 30 2 .1 

Stnol•ing by husband's fatber in the home 3 .5• J ._• 

Occupational exposure to iron or other metals 2 .8 1 d 

tRR of each factor adju.sted for other two facton after excluding the patrs 

in which one of the facton had unknoa'n values 

•q

394 li . Bhimisu .t al . 

places 


In this studr we found a po.itive association between lung eancer in 

nonsmoking women and the smoking hutory of family members, especially that of 

mother and husband's father. As Japanese children nsually spend much longer 

time with their mother than other family members do, mother's smoL•ing may be 

a representative index of passive smoking before leaving home at around 20 years 

of age Rerently we found that the saliva cotinine level of nonsmoking school- 

children is not high when their fathers were smokers but high when their mothers 

were smokers in ~Iiragi, a district of northeastern Japan (unpublished data) . 

After marriage, 35°0 of women in controls lived with their husband's parents . 

The final proportion of control women whose husband's father smoked cigarettes 

in the home n•as as small as 8%, but that (18%) of eases was somewhat larger . 

The husband's father may have retired already and may have stayed home much 

longer than the husbands . There is a possibility that Japanese women may be 

more frequently exposed to the smoke of cigarettes by their husband's father than 

that bv their husband . 

Ft'e assessed the total length of period which a woman spent with her husband 

from the length of the period of marriage and the hours during which she lived in 

the same room . but no difierenoe was found between eases and controls . 

No dose-response relationship was ob.crved between the risk of lung cancer 

and the history of smoking of mother or husband's father . Usually the respondents 

remember .rbetber their mother or their husband's father were smokers, but 

they may be unable to recall the exact number of cigarettes smoked by their 

mother (especially in childhood) or husband's father in the home . 

It has been suggested that bet .-caratene and preformed vitamin A decrease 

the risk of lung cancer (Smith 1982 ; Hinds et al . 1984) . We asked a very simple 

question concerning the frequency of green-yellow vegetable intake, which has 

been referred to as a protective factor against lung cancer in a large cohort study 

of Japan (Hirayama 1962) . No association was observed between this variable 

and female lung cancer risk in oar stody . Most of the respondents had green- 

yellow vegetables very fr .quently and we found no difference between casss and 

controls . There was no do .e-response relationship between the frequency of 

intake of Ereen'yello.r vegetables and lung canoer risk . 

We also assessed the effmacy of vitamin supplements over a period of more 

than one year in this analysis, and found the risk of 0 .5 . However it was not 

aatistically significant . 

Other dietay factor such a : .itamin C and cholesterol may be tslated to the 

development of lung eaaoer (Hinds et al . 1983, 1484 ; Byers and Oraham 1Q83), 

but no appreciable association was observed between the risk of lung cancer and 

the intake of food items listed in this study . To evaluate the effect of dietary 

habitc . more precise measurement of food intake is needed . 

A slightly elevated risk for disease history of silicosis is consistent with the

\ 


kii-ome bias in our study . Lung cancer cases were not derived 

from general population but from the p,uientF of a limited number of hospitals . 

The proportion of adenoc,rrcinornn patient, in our aeries was ten percent larger as 

compured with that :n total lung cancer Itatieuts of this area The proportion of 

scluamons cell carcinoma shotced in npposite tendency (Kar,uaR a 1983) . We 

electPd the control ; from the same hospitals considering that both cases and 

controls in is Qnte hospital may have similar backgrounds . Hon-ecer . one of the 

hospttal uu-, a can, - Itn,Nital and we had to include many breast cancer patients 

in the controls For this re .t~on we compared the status of passive smoking among 

the brrivt cancer patients with that among other controls . but we found no 

difference . Futthermore, the risk of lung cancer for the survivors of cancer of the 

brew~t a,>_< not high when assessed by the data of a population-b,ued cancer 

rrgistn (Takano and Okuno : personal communication) . 

Our study showed that the exposura to tobacco smoke from household 

members (i .e., mother or husband's father) could be associated with female lung 

cancer. As the precise situation of passive smoking in the home or other places 

is still unclear, further studies are needed to clarify the significance of passive 

smoking in relation to the etiology of lung cancer in Japanese women . 

AtknowkdQments 

We are ftrnteful to Ms K Htrose of Aichi Cancer Center Reaerrth Institute and Ms . Y . 

T,tl::ihwhi of Tohoku University School of )ledicirte for their technical assutance . This 

atudy x aa supported by a Orantlin-Aid for Cancer Research from the )linistn of Health and 

Welfara ((',nsnt Number 57S ) 

I) Al :itw, 8.. Kato . H:. k Blot. WJ . (1986) Passive anwlialt and lucsE canoer among 

Japanse romea L4rar . iiw .. K . d8W-4807 . 

2) dreslow, N .E. k Day, N .E. (1990) The analysis of ore-sotttrol audiea . In : 

Statistaos/ Yei" it Ca,Ker Rres>ti1 . Vol . I . IARC Scientific Publicatwns No . 32. 

laterrutional Aratcy (or 8tiarah on Cutaer . Lron . 

3) Breslow, N .E .. Ihy, N .E .. Halvonen. K .T .. Prentice, R.L. k Sabet. C. (197B) 

&timatioa of asaltipk telaeire ewl trJnctiocr in eate!»d eaar couuoi studies .lswee . 

J . B/iJcrwiot . . 1M, 299-J01 . 

4) Byers, T. k Graham, 8 . (1084) The tpidemio)oU of diet and canaer. In : Alrauar 

in C4rcrr Rneoral, Vol,11, trditad by G, Klein k S . Weinbous+e, Academic his, 

4riando-Fbrida, pp . 1-60 . 

S) CorreA, P ., Picl-le, LW, lroatham, E ., Lin . Y. k Haeasttl. W. (1pdJ) Pa:ioe


396 

H Sbimitu et a) . 

staol•tne and lung canoer . Laacrt . 2 . S9S-597 . 

6) Finlelftein, M Kuaiak R . k Suraayi, (7 . (1982) 1Lottaliq aawng ciaen rttroei .int 

a-ori:nxn'a ootapensation for ailteosu in Oatatio : 1940-1975 J• actyp -11ed ., 24, 

66J•66" 

7) C.+rfin{;al . L . (19,i1) Tttae tnnds in lung cancer tportality amonj tsontmolert urd a 

note oo pulis•e aaioltng J . Mat . G=Km IRSt ., M, 1061-1066 . 

8) Uarfinl:rl, L, Auertach, 00 k Joubert, L (1985) Lo .olantary tmoking and lung 

canc.r A ca.rcoutrol study J . .at Cancsr laat ., 75, 4b3-469 

9) Htnds If W ., Kolonel . L .N ., HanL•ia, J .H k Lae, J . (1983) Dietary cholaterol and 

lung cancer rial: in a mu)txthnic population in Ha .aii, lat . J . Canu+ . 31, 727-732, 

10) Htnds . >l .W ., Kolooel, L.N ., Hankia, J .H . k L.e, J . (1964) I?ietary vitamin A . 

crroten-, vttaatiu C and risl of lung raacer in Hat :ail A .a.* . J . lpede*etol ., 111, 

_'•=-•23 ; 

11) Htnrema T(1?41) NonarnoLing rivea of beavy smokerza have a higher ruk of lung 

canc r .1 studY from Japan Bnt m.d . J ., 2{2 . 183-185 

12) HiraYerna . T(19d'2) Epidemto)olpcal upecu of lung cancer in the Orient . In : 

Lung /anorr 195 :.' . edited by S Lhil:•arca, Y . Hayama A K. Suemasu, Ezcerpta 

lled ca Am :terdam-0zford-Prtnceton, pp 1-13 . 

13) Inoue R Ohuula . T . . Shimura . K . k Htrayama. T . (1986) A ase-conarol study of 

lung cancer Luag Car«r, 26, 763-767 . (Japanese) 

la) Kabrt . 0 C . k 1t't•nder, E .L (198a) Lung cancer in noaamoJcen . Csaeer . 53, 1214- 

1321 

15) K .ruawa, K . (19d35) Distribution of histalog•'scal typa of lung cancer in Aichi 

Prefecture Jap J CAot LL . . 44 . ®09-813 . (Jap.ne.e) 

16) Koo, L( . Ho . J .H . k Saw, D(1984) L passive atnokina an added risk factor for 

lung cancer in Chineae sottxn J . sp, elin . Capzer Ra ., 3, 277-283 

17) Lee . PN . Chamberlain, J . k Alderson, H .R. (1986) Reluion.hip of pasive smoking 

to n,l; of lung cancer and other amolcing• .uociated di+eaus Brit . J . C4KCe* . $4, 97l05 

18) LS•nFe E . Kurppa . K ., Kristoferson . L ., Maller . H . k Sauli, H . (1986) Silica dust 

rnd lung cancer Results from the Nordic oecupauonal mortality and cancer incidence 

relritteri J . r,at Cancs+ Iru( ., 77 . 683-889 

19) >lat :ukuri, S. . Tomituso, T ., Kitano, N ., Seino, Y ., Hamada, H ., Uebihashi . M . . 

\akajima, H k Htrata, Y . (1984) EEffects of environtnental tobacco smoke on 

unn.n• cotinine eser.tion in aottsmokert . Evidence for paaice amoking Veu 

Engl J .lled ., 311 . E28-832 . 

20) Nalatoura . H ., H.aaai, A., Fujimoto . L, Matauda, M. k Tauithi, R(1988) Relation• 

•hip between amoL•ing and the four najor hitiolofic tTpes of lung cancer . Luag 

r'nru.r . 26 . 137- l 1d . (Japus . .e ) 

:l ) Shimizu . H . (1983) A un-oootrol study of lung canoer by histulogic type . L+tng 

Cax


Ri•k F,trt,v• for F--iu,il, LuuR C .uir,r 397 

13a-'131 

: t µ'u . A .H . . HeuJewn B E . Ptke, \I C~ l*u 1l (' ( If)tt)l ~ntuktnc uttKr nal : 

fuuurs for luug cuu"r in wow.n J~nr f.„rcr lKit, . 74 , ~7 al


11

Stockwell, H .G ., Goldman, A .L ., Lyman, G .H ., Noss, C .I ., Armstrong, 

A .W ., Pinkham, P .A ., Candelora, E .C ., and Brusa, M .R ., 

"Environmental Tobacco Smoke and Lung Cancer in Never Smoking 

Women," Journal of the National Cancer Institute 84(18) : 1417- 

1422, 1992 . 

In 1992, Stockwell and colleagues published data from a 

case-control study of nonsmoking women in Florida . The authors 

wrote : "We found no statistically significant increase in risk 

associated with exposure to environmental tobacco smoke at work ." 

However, they failed to present the data associated with this index 

of exposure . 


I 

h 

1 

Environmental Tobacco Smoke 

and Lung Cancer Risk in 

Nonsmoking Women 

Hcathrr G . Stuckts•cll,' Allan L . 

GaJdtnun, Gur), H. Lyman, 

Charles 1. Nuss, Adum Iti' . 

Arm .ctrong, Putriciu A . Pinklrntn, 

Elizabcth C. Candclora, 

Marcia R . 19rusu 

t .ckrrounQ: Exposure to environ• 

tseatal tobacco smoke (passive smok- 

I.t) has bcen suggested to be a cause 

•f lung cancer, although eariy epide• 

ot.logic studies have produced Ineassistent 

results . Pa s .d tlrouatts- `~ 

tict, Colktr of iwbtic Hcaln, . U .i .crstty ot >;ana 

Fsaeid, . t.mo.L n- 3xtiAsrac . ~.f 

CA 

RErOR75 la l7

csrciaomt of de IYnj (latctaatlosl 

Ctauifrcalion of Diseases for OwcoloYy 

Codes 162 .2•1629) that wu Iuinosed 

•et..ten April l, 19E7, sad fcbnary, 28, 

1991 . and if they resided at tMe time of 

Iiapnosis in a 2K'-ounl ; area ia tratral 

florid . These women ucrc idcnlified 

tlrrourh the tumor rcFisuics of area "• 

iaital% and thc floriJ . Canccr Data SW 

t,cm of the Statewidc Cancer kcgrstry . 

Conuol s,ubjects wrrc community bascd 

sad Mcrc identificd through rsndom• 

Jijit dialing All casa patients and con• 

trol .uhjccts Mcrc lifetime rMnsmol .erN . 

cLcfineJ as Iuvint unnkW fcx a totat of 

k~a than h snonths nr kavinj a>rwlcd 

(cxs shan tfpl cijarcr(cs in thcir Iifc• 

timCs 

The umr+lin ; status of potential nac 

ptient, in the atudl was enn(irrned at 

teverrl at .~ca Oncc Shcr,e individual, 

wer : iJrnriG,;J hy thrir hrrspital crr thc 

Statcw idd C'aneet Kcyi .tr) rceord .,thcir 

ftmolink status was eunfrrmcd when 

their physician wa .s eonl .cted fur per• 

taission to interview, again at the time 

of initial contact with the patient or nezt 

of kin, and, finally, at the eommence• 

ment of Ihc interviev . . In adJirion, the 

laten'uw eontained questions retardinj 

esperimentalion with tobacco, desijned 

b elicit in a aculral rnanner any prior 

trndisclosed tobacco use Any potential 

case patient whose smoking ssatus could 

wot he confirmed vvs escludcd, Of 

thou found to he eli=ihte, e0% of ths 

eut patients or their nezl of kin agreed 

to Ix inlerviewed The tmol•inj itatus 

of eonarol wbjocts w as determined dur• 

int random-di;il dialint and verified 

during the interview . 

Trained inurview•ers inurviev.ed casc 

paliertss and control subjeets either in 

pcrson or overthc telephone . When sec• 

essar% . questionnairca wcre ruiled . Of 

the ease palicnt inter .•iews, l1'>E werc 

obtaintd hy in•person eorsuct, 51% by 

kscphont, and 8% by mail . Of the eon• 

tro! tubjen interviews, 53•8rl %LYre ohuine 

;i by in•person contact, 15 .9% by 

teiephone, and 0•34E by aaaii• tatormed 

cvnsrnt was obtained from t1u esic pa• 

tienis and control tubjens prior to the 

intcrrie>~s according to the guidelines 

of the University of South Florids inui- 

Wtional Revicr< 8oard, The iaterview 

i.cludcd questions on environmental toa 

bacco cmoke esposures at bome, on the 

)o6, and in aocisl uttings . IJ csse pa- 


tieasa were bo 11I b be iwservitaed tx 

wcre ieceascd . aurroiau teapoadcats 

(prirnarily ltusbands and children) were 

satcrvicwcd toterviews of tunotste ntpondenu 

were .ecxsury (or 66 .7'!E of 

the case patients 

Odds ratioa (OiCs) were calcutsted to 

csuimate the relative risks Multiplc bo•• 

gislic regression analyses were per• 

(ormcd using the SAS L.OCi1ST7C procedure 

(SAS Institute . Cary . N .C .) . 

Nlnety•fiive pcrccnt cortfidencc imcrvala 

(Cii) were calcvlated from tMe lotistic 

tnodets . The chi•square statistic was 

wcd to text (or trcnd, 

Ruults 

The stud) p{omewkal oldet and lud fewer 7tart 

of tomul .ducalion thu, vontrols, with 

a tijniftcam trend of is,creuinj lung 

cancer risk with dccreatint years of 

fchoolint (P . .tl19) AMwss half of the 

uu patients and control tubjcns irad 

lived in Florida for at ieasl 2/) years 

Table 2 iwditatcs the OKS and 459E 

Cis associated with ezposure to cig .• 

rettc tmokc fsom parenti, tihlinta, Au .- 

I+ands, and o(her Isauuhold membcn, 

after adjuslment (nr age . racc, and 

[ducatKfn . UnctpncCd Kdividual, wcrc 

Ua.c with ae lanuscbold envirrmrncntal 

tohacco unokc etpowre, Wc der .crihc 

exposure i . ecrnu of uswkc•ycar ., dc• 

fined u• the sum of the reporscd years of 

e :pnaurc to eitarettc tmnkc (nxn each 

amnker in thc househnld We rnnxidcred 

arswlc•ycan% to hc a moee reliable rr.casarc 

of exposurc than pack-years, aincr 

ttudy panicipants had ltss difficulty realling 

tha Rumber of years they lad 

lived with someone WMo uenoked tlsan 

recalling the tsurnber of cigarettes per 

day to which they had been ezpoud• 

Smoke-years were subdivided into thres 

eatejories of approxienately equal size 

Tal6k t . OnarRrmw~ st sIw_w1 cMnaneriwic. a( are rrinw "/ tata.eni WAJcV . 

C ... Mrir.n ( . . Ztnt' C.wnt ..b)cet. ( . . jUl)• 

Ca.raar+wic r~to s !+o ~r 

l,cr 

wt

1or both wfy aad adult years . Tis distribution 

of unoke•years of exposurc 

vas snuch lowr:r tor sarly ytan, pri• 

wrily beeause ptrtieipents te*ded to 

/ive with tpouscs for anorc ytan lhan 

Mey had lived with their parents• rtar+lt• 

404 in bwer eutoff points . 

Lant cancer riek estimstcs for .vomen 

who wcre ssposed to environmr :asl 

Iobacco smoke during childhood and 

sdolcsccncc sre shown in Table 2 . 

When we cakuh'ed the tisk sstociated 

wUh esposure to smoke from family 

wcmhers on an individual hasis 

(rwother, Athct, eihlin=s, and others) . 

Mcrc wes a slight incrurc in risk fnt a11 

trrfwx.ura., althtw ;h the inerea>,e% ir, rial 

were t+nt tastiraically sitnificant . F1e+w• 

e.rer . %%hcn we alculated risk ncewdin ; 

1o cmcste•yrars of expowrc, which rc• 

lkn,, total ccpcrwrc to unokc from all 

brw .cMilJ memhera, a >itnificantly clc• 

raled ri" of 2 .4 (9S'% (.'1 a i .l•5 41 was 

ot+aervcd for women expoacd 22 years 

4111' more . 

Table 2 also shows the effect of en• 

wironmcntal tobacco smoke exposurt 

iurine adulthood on lun; cancer risk . 

Women who lived for 111 or more years 

ef their adult lives with husbands and 

•ther individuals who smokcd were 

found to Iavc ae elevated risk of 2 .4 

(95'i ta a If we eonsidere.d 

only smoke exposure from husbands tor 

40 or more smoke•years (data not 

shown), the riek ealimate deereascd 

slijhtly to 2 .2 (95% Cl ∎ 1 .0-4 .9) . 

Is terau of sout IiGetiree rrsaoke•ysan 

ot expcwrs (Tabte 21, ao nIt+rifresst exaeu 

risfs were obterved for wornen re• 

pning fs+ver than 40 liftsirwe saokt• 

yean, but wwnen teportinj 40 oe teore 

years of exposure experieated an e)e• 

vsecd lrng eanrer risk of 2J (959E l:.•l . 

1 .1-r .6) . 

We elso r:xamined the relationship 

between the lung cancer ritk assotinted 

with environmental sobaceo srnokc es• 

poaurc and lun ; cancer tslliype . Sinct 

61 .4% of the lung ancen is the study 

were adenocarcinomas, all fant anr:er 

kiuolotien orher tMn adenesrareinoma 

wore enrnhined in one graep for anal• 

yxi>_ Rie,k craimatcc for snu+k.c-yeara of 

expn .urc were aleulated esparatcly kx 

the two Croups, and (he results arc 

shown is Table 2 . 

Pot womcn h ith .denocareinorna . the 

risk& wcre sJiFhti) elevated for all ate- 

Rnric+k of smoke exposure, fwt the tccuitt 

did sot achieve ttatistical 

significance . Women with fwn•adenoeareinoma 

lunt ancert, on the other 

kand, showed sitnificantiy elevated 

risks when their exposure to environmental 

tobacco smokc was of lonL duration 

. The OR indicated a threefold 

increased risk of lung cancer (or women 

who rcponed 22 or more rmoke•years 

of exposure from parents, siblints, atxM 

others during ehildhood and adolee• 

ccncc (OR ∎ 3 .4 ; 95% Ct . 

Similarly• women with 40 or more years 

of adulthood exposure to unoke from 

Iwrxbands aad oeb,er bo.es>rotd a.pwkery 

s:pcrie .ced a eignifieaat etsvatioa is 

risk (OR a 3-3i 95% CI a 1 .1•4 .1i3 . 

Wken total lifetiRne sspoars to savironmental 

smoicc was otesidend, thc 

ORwas3 .3(95teCt .124 9) tarthe 

lriRhest expowre kvtl, for womea vith 

rron•sdenocarcinr+ma lurti cancers, there 

was a statiuicatly sipnifirant trend of 

iracrcasing risk auaciatcd with incrsasinR 

smcrke•yean of sxposnrr for each 

typc of e :posun (cfiildhood . adulthood, 

.nd lifetime) . 

Sinee sunoCatc rrspowdents wcrc required 

for ahnut two IAirds of the ea .c 

paticnt intcrviews• we iaveslipatad 

w#cthcr the fknuree e,f the ar .e pallent 

intcrvicw (xel(-respnersient verwe, wrrn• 

5atc re4ondcnt) sffened the riik cFtitautex 

. Surrogate rrspo .dra,s for cau 

patients were divided iato two jroupt, 

"Muxhands" and "oaher surrngate% ." 

the tarter trrwp conxistini ; primarily of 

aon,, and dauthten . Tbc tosHlts of Ihis 

an..lyaix arr: shown in Tahie ` . $eeauu 

the'urnber of respondents ia twme ate• 

:oria was vsry srtult, analysis of risk 

associated with exposure to tmoi.e from 

individual household rnemhers is 

limited to fathers and (tusbands . In eomparison 

with thc risk ectimatcs for 

women whose interviews were "m• 

pleted by themulva a by ifcir !wsbands, 

the ritk etiimata kr woaxn ir 

the "other surrogate" respondent att• 

sory were eonsidcrably krwer . This rt• 

tult wat trve both far tisk associatcd 

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 

AN Irnt a . .rn AJc.ocmi.awr An ~ crn r pn 

kary+art \" .} OR' r :t7 CI / f, . a .+J OR' ..t4 (1 P tw trt*d (TR' trt+} (1 P i,w tre.A 

ftpwac "r 

f4,4A.y 111, 0 64 1 1* 0< .1.k e 1 .7 40-A•S .2 

isr4•r 1-1 rF-2i t .t 6 .9-2c 1,4 

tAi ~t, nd .+4crs i 7 qy-1 v 1-1 *s-2.7 tA Rb~ .7 

11Jt.1,n r A "2.7 21 s•3ac 

tawks 

caiuh . .rQ/.dek+cc.a (p.+ra. 

~t~~) 

tK•21 

t F 

1 .1 .t2 .a t ,L~A 

I t 

1 .3 

r.4I -% 

t.3dA 

s»` 2A 1 .1•S .J .tlt 1 .7 ~ .1•,tA .f91 X4 ( .1•IO .F .WI 

AMhlu+~ (h+4..& 844 0tficr .t 

t . r .. aa A : 1 .7 •tt .7 1 i ts-es 

~ .« 14 2b R7-S a 

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Au NrnW.r rr .,o..td r,~rrrr 

r+ •w•2 S 1 .2 . -9 .2 7 1.2 s s•3 .e 

1 . 1/.7•s . 1•2 Is • ..as 

r. .o t .td F oru I .7 or< .~ . .n1 I2•1~ uut 

'OR . aii.rut 4w aCt, raee . ar

Tah/. 1. 911140 ar n.i ....rts1 rir ..et : .. Iry .. .cn ri.1 .l .wrw.i iwt 

.rc. .•l. .t w rr..+.e .( wre lr4wi Ire ..w. 

ti. .r« .l ar< W•rr Y. .+vier 

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(Y .Mw.rc 6u^ry OR• K41~ CI oR• fRf C1 OR' flS CI OR• tt4 f•t 

tlar. ..nr' fe+Pao 

f .r4y 3 .2 •9•11 .1 2 .t/ .4at.x aA i-L11 27 en•7,? 

/MrJ..J 

>

i.diated thau the escivsion of adrsoearci.omu 

from thcir analysis rrodMcrd s 

sutisyitally sitniRtant linear Irrad of 

i .crcasing risk with iscrtasiaj ss- 

'osure . 

!a an i>.vestigation of ao+-adeaoearcinoma 

iung ancers in .autnokinj 

Athenian women, Triehopoutos st al . 

(J!) rcpnncd a risk estimate ot 2 .4 for 

women who%c Mustunds smoked itwtr 

than 21 citareHCS per day sad a risk 

Wirtultc oL3 .4 for women whos< t+us- 

Irndr smoktd sore Ilun 20 eijarettes 

rer day . As aucoeiation betwees marviajc 

to a smoker and an inctuscd risk 

of amail-ecll and squamous ee11 lung 

areincrmas wa,; sl .n rshrcrved is a stady 

c+f Ss'cdiah womcn (12) For otAcr lung 

canecr ectt typrr, in the SMCdrsh study, 

t1c ti/.ks Wctc clo.c ai unity ascspt in 

the ea+.c of women with high espou+re 

kvc) ., wbkw ri>,k4 wa.s tkluhlyd . A study 

trt lifetimc wc/namuking wnmen in HunC 

h:anr by taw ct .1, (13) .huWCd that e .roe.urc 

/o envimamcnt,ll toMcco smoke 

ws.c as,ociated with an elevated risk of 

aquamous cell and large-cell eareinomas 

. These results conflict with 

tho+,e ohscrved in a multieentered study 

3s the United States (4), where an ele• 

vated risk of lung cancer attributable to 

passive smoking was limited to patients 

with adenoeareinonu ; these i>

. / , 

A m.Mke.rsr aasrrarsl M .fr . Cr .arr 

(irls hn 1JW), 

1901 

0) i.aau-w roT, T..a ..ns. WD, v .aa... u• 

L4 4L• tUnt irfue! Md teloMSry Y M"aeo 

Nr.llc i. nts ls ..uioi4 N Eaj1 J Mrd 

fVAV.A,+, twu 

MI G+a.. R Fx .u LW, F+wrw.r E r* .u : 

Fwivc .wekl .t aad tv .j u+cct IA .ctti 

= avt SV), Iw~ 

(II i..r,wi! 1N' . W,u . .k AJ . kvt .a .. RH 

fwntui.c tit r . .! tiisrir.c Fr .+++Y .w .A• 

i .t .s c..ceY .+ .1 lycati 1 .ct2-ti" . tM~ 

V) Wt, AH. Hr~+avr IL P .&i MC, vT a= 

j.nliuj s+td a4r rnl (ac„++ i .x b*F tl., 

es 1r su.n .')NCt 74 7J)-7t1 . lwt.t 

f•l (5+.+ .+.r N& Iurt, I .W . MA ..r Tl, f-, 

u: T1c .dNir wf p+..+s v.i,.; M br4 

p.cor esi,err, tte . .n UcY : .,ri11, Iwtt, 

eMt Gwsw .at, (- At-v O . M .w at t- M• 

.wiWary .riin ; rd ir .i c..cnA ou• 

.wrw,i .wir aM(1 t~,ahunv, Iwt~ 

4111 TlN1M/AMh,M l) . K ./ AAIM/4 I- fr . . . .t. 

t-tT u : t .ws c..ctT a.J (w.+ .Y r..ai.F 

iu 1 f..ee+ 27 . t .d, Nha 

lla r't.rrutu+w . G . elrr .wtt' 1'L li .'t .ncvw, C : 

!wd tvnj a .cn M i.eJnA 

Aw I k{.wk'mi,~i 12! 17- :J . Irr+r) 

/1,1t t: .k . If, 14l JH . SAM D t t .l McewN• 

zbc•w. ., tvw.ivc u.w~tnt .wJ Nrnak t~t 

VRt CIMVi rlal !II Mt MM• .R+,~I,Ai l~~• 

a .+,c rcm,k+ l .r 1 C.nccr 1V IE?-InV, IVl;) 

//1i t_nu TH . Ko»to IT, Wn ., . CM . ti î' . 

t1AN)lifl; . refYiMC Y9,uEMj lr+d kM,11 .gK1l 

erpr+ i. It,nt o .cY* is Hont Ka+t Clikeu : 

.nw,c. ltr J Crctr 4 :67.Ud7X. IVY7 

Second Cancers in Patdents 

With Chronic Lymphocytic 

Leukemia 

LoEs B. Travis,• Rochelle E . 

Curtis, Benjamin F. Narthey, 

Joseph F. Fraumerti, Jr . 

Ieckjroyxd: Reports te dale have 

pr.vided widely diverYtat estimatea 

sf the risk .f sccond maligaaat .eaplams 

la patients with chronic Iysa- 

'Mocytic leukemia (CLLI, raatlaj 

Ir .m aacer t/eficits to excesses st 

twofold to threefold . l+rrpose: Orr 

purpose was to ettimate the rlik af 

secoad primary eaacers fotiowiag 

CLI., t.tlliiiat population-based /r- 

•ar retistriet, sad to determi .e 

wkether site-specitic excesses might 

be ass.ciated with type •r iaitial 

lrealsaeat f.r CLL . Methods : We 


•satysed date f.r pJSf patieats 

di:ra .sed wltt CLL as a first priaaary 

rxarer ètweea 1173 aad tlit, 

who wcrt rsponed te e ..c of sise tYror 

registries participatinj la the 

Natioaal Ca .cer Iastiiute's Srrvellls 

.ce, Epidemiology, sad Ead 

Resrlis (SEERt protrasn aad who 

atsrvived 2•r snorr sa .atht . SEEK 

filet wert scarched for (avasive pri• 

wary .uliGoa .cies that developed at 

kast 2 snonths aftcr the t.itial CLL 

d[alt.rsis. Nes>rtu : Cwnparsd witM the 

te .erai popufatioa, CLL patleats 

dcmo .strated a allaificaatly (a• 

crsased risk .f developi .g all fer .wd 

tancer: (tt10 .trserved ; .Asrrred-Ioexperird 

rmllo iU/E) a 1 .2tt ; 1Sr4 watideace 

i.terval (CIj s Lif-1 t7l >wikalficsat 

excesses were • .ted f.r 

e.acen af twe 1r .p (O/E ∎ I .f0) . 

brain (O(E . 1 .951 . aMd e,vt (Ialrsrecutar 

snetaaom :i (O/E a3171 as well ak 

mslitnant melanums (O/E a 2 .79) 

a .d fiudptJn'i diuau (O/E a 7A91 . 

Cancer riti., which did sol vsry sceording 

to t .ltial treatmeal tates.ry, 

wat also eoastanl across all time ialcrvals 

aRer CLL diag .osis. Ce+aelwsionr 

CLL patieats art at a sltaiAantly 

Increased risk sf developing a 

second maiizaant seoplasm . The pattera 

•f cancer excesset suggests a 

susceptibility state pertnittinj the tievetopmen( 

•f seleclcd record aaatitsancies 

In patients with CLL, perhaps 

because sf shared etiolo=ic fad .n, 

ImmunofoCic impairstte .t, sad/ar 

Nher Influences . Althouth .ur res.lu 

do sot sut=est a ttront lreat .eat 

eRect, srori detailed studies of second 

tumors In CU,L are aeeded to lavesli• 

&atc lhe role of radiation therapy and 

ehemothcrapy• lJ Nati Caatxr /ast 

814422-1427, 1ff21 

ratients with chronic ly/nphocytie 

kukcmia (CLL) cxhihit a variety of imsnunolotic 

pcrsurhation>, (1•I) that may 

iacreaae ihcir riik for second malignant 

aanplasms . 'flM occurrence of f .milial 

Ct.t- snay ai>n sug&eu, for some auh- 

jeC1A, ènelic determinantR (S•7)- n.ch 

as Ihosc that rnderlie other am of aeui- 

/iptc primsry eancers (d.4) . Moreover, 

radiotherapy and ehemotberapcrrtie 

rtenls tnxy also contribute lo tubsc• 

"at trutiSnancics awoRE aarel wrvivors 

(10) . h)i islpoeunt to e{arify tlc 

risk of sccond nactrs iu CLt patienu 

kausc of the potc .lial i.r¢tact ar'a . 

/ient ma.s=ement, folloMwp . awd sur• 

vivat . liowever, various teporu to date 

Aave prewided divcr0eat etuirnatai of thc 

nccuncncc nf seccmd malipn .ncic> in 

CLt, prticnll, esnting frcxn cancer dcfi• 

e:itt to cxccar.es of twofold lo ty reefold 

To funher expiorc and quantify 

thc ri .k of secrnd eaaccrti amnnF a 

iarY,: a.snl.cr of CU . patieatk ia lh, : 

stnt•~ta) perpulatics. .ad 60 csa/aiac aa>,r .ciatiewst. 

af tisk with iaitial IAstaf+~ . ac 

ct>t+Juctcd a errvcy cr1' tNCwc tMan WKxt 

arrA whjctu. eer.Ntcd k+ th,.• Natinn .t 

('anccr (raaitutc' . Survcitlarcc . Epi . 

ek:miuitrry . and End llcsult . (SEER) 

Prorram' from IV71 thtourh IVK)i . 

Siacc CLIL palicals src frcqucatly 

trratrd naly evith aakylatinp aFc'at . r•ithewt 

ibc ennftwndinp, ctfcn~ . nf rad,.thcrary 

. ehi,. =rnup of paticntu ptovidc+ 

a apcciai opponunity to uud~ tbc latc 

acquctac of tflleae rlrup, 

Patients asid Methodt 

We aaatysed all patients diataosed 

with CLlL as a 6rst primary au,eet be• 

twexn 1973 and 148b who Wcn reporle,d 

10 onc of .Sac populatioo-based ancYr 

.ejistries of the SEER Projram aad lrrvi.red 

2 a tewre wronths. Sue1 «Yiscrics 

tndudc albe.e in tAe raetroQoliean arem of 

Rasri .ad l.rwry tn• tw :: .ni .dd eLr M . 

Iw : . rv,TrrJ lwa• 4 . tw: 

1_ H t'r..:, R . k('orte. l F . Farraxi k 

ek(+if.. .4d..e! sy M-4ltwit+ Nnr+aa, nni- 

.L ., .d ('.a„ 6&t•) SSt . It F /ta.Lr. (c .,a. 

ti,Mn,k, litaactt. 1: .n,7lt,.a h .+r,w,• I),,n.. 

w( ('.+cn PtmlliwM /ad ('twrotl . Mtrrut Cwerr 

(a.+kw ., Fktlc~d+ . MJ 

Wc arr "4" /n tL . l4ak IIceM tl.Ttvn .r 

4wra (M .. It.rbkca McKsn wW Dr . llntc. f. 

(.yweY l i . dau trnkv,l, to Dr.. l." idn . NeN 

C.t .r .w . ad 6lsrku LMw i.r a+cal re.in 1 

w,• sr+,+, . .eri{c a.d W, M, r„t+rt ; t'r.ra„w 

. .J t


12

Wu, A ., Henderson, B .E ., Pike, M .C ., and Yu, M .C ., "Smoking and 

other Risk Factors for Lung Cancer in Women," Journal of the 

National Cancer Institute 74(4) : 747-751, 1985 . 

In 1985, Wu and colleagues reported on a case-control 

study of women in a Los Angeles, California tumor registry . For 

adenocarcinoma, the authors wrote, "we did not observe any elevated 

risk associated with passive smoke exposure . . . at work (RR = 

1 .3 ; 95% CI = 0 .5-3 .3) ." 


Smoking and Other Risk Factors for Lung Cancer In Women '-1 

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' , 

ABSTRACT-A oas&-control study among wh+t• won»n in Los 

Anfl .lau County was conduct .d to inv .stipate tM rot . of tmokinp 

+nd othsr factors in tha etiology of lung cancyr in womirn . A total of 

149 pati.nts with ao.nowrcinoma (ADC) and 71 patt .nU with 

squamous cell urc noma (5CC) of the lung and their ap.- and 

sea-match .d controls were tnt*rvi.w.d Personal cigarette smoking 

accountrd for almost all of SCC and about halt of ADC in ttm study 

populat on . Among nonsmokers, slightly tlevat .d r.lat v . rtsk(s) 

(RR) for ADC were observed for paas vw smoke rxpoaure from 

spouse(s) IRR=1 .2, 95'r conf d .nce interval (CI)=0 .5 . 3,3] and at 

work (RR=1 .3, 95% CI=0 .5, 3 .3) Childhood pneumonia (RR=2 .7, 

95% Ct=1 .i . 6 7) and ch ldhood .xposura to coal burning (RR=2 .3, 

45% CI=1 .0 . 5 5) were add t onal risk factors for ADC, For both 

ADC and SCC, increased risks were assocuted w th decreased 

intake of S-carotsne foods but not for total preformed vitamin A 

foods and vitamin supplements -JNCI tpb5, 74 .747-751 

Lung cancer is now the fourth most common cancer in 

women (1) and has been projected to be the lading cause 

of cancer mortaliry among women by the mid•1980's (2) . 

Causes of lung cancer, other than cigarette smoking (3), 

have not been clearly identified, but associations with 

exposure to passive smoking (4-6), exposure to combustion 

products of heating and cooking fuels (7), and 

occupational exposures (8-JO) have been suggested . In 

addition, lung "scamng" (11) and a low dietary intake of 

S•carotene (12-1 t) and preformed vitamin A(13-17) may 

increase the risk of lung eancer . 

This paper reports a case-control study of ADC and 

SCC of the lung in white females in Los Angeles County . 

Each of the above•mentioned factors was investigated . 

METHClqS 

Female patients diagnosed with primary ADC or SCC 

of the lung were prospectively identified by the CSP, the 

population-based tumor registry for Los Angeles County 

(18), between April 1, 1981, and August 31, 1982 . On the 

basis of information collected routinely by the CSP, we 

limited eligibility to white Los Angeles County residents, 

with no history of cancer (other than non-melanoma skin 

ctncer) and under age 76 at diagnosis ; we verified these 

variables at interview . We also excluded cases if they were 

born outside the United States, Canada, or Europe ; were 

not English•speaking ; or were not residents of Los 

Angeles County at the date of diagnosis . 

A total of 490 eligible ©ses were identified . Of these 

patients, 190 had died or were too ill to participate by the 

time we contacted their attending physician . Permission 

was granted to contact 272 of the remaining 300 patients . 

Eight patients were not located, and 44 refused to be 

interviewed so that we obtained completed questionnaires 

on 220 . On the basis of information on the CSP 

absuact, no significant differences were noted between 


those interviewed and those not interviewed in terms of 

age, marital status, religion, and smoking status recorded 

on medical records . However, those who were not 

interviewed were more likely to have distant metastases at 

the time of diagnosis (58`£) compared to those who were 

interviewed (11%), Comparable percentages of eligible 

SCC (43%) and ADC (46%) patients were interviewed . 

We selected one individually matched neighborhood 

control for each interviewed case . The control had to 

fulfill all the criteria given above for cases (with reference 

date taken to be the same as that of the matching case) 

and, in addition, was matched with the case on date of 

birth (t5 yr of birth date) . Our control selection 

algorithm defined a specified sequence of houses to be 

visited in the neighborhood where the case lived at date of 

diagnosis . Our goal was to interview the first eligible 

resident in this sequence . If no one was home at the time 

of the visit, we left an explanatory letter and made a 

follow-up visit after several days . For any patient, 80 

housing units were visited and 3 return visits were made 

before failure to secure a matched control was conceded . 

In 150 instances the first eligible person agreed to 

participate, in 55 instances the second eligible control in 

the sequence was interviewed, and in 15 instances the 

third eligible control was interviewed . 

Cases and controls were interviewed on the telephone 

with the use of a structured questionnaire designed to 

elicit information on personal smoking habits, exposure 

to passive tobacco smoke, lung diseases, dietary intake of 

vitamin A, types of heating and cooking fuels ever used, 

and reproductive history . We also obtained a lifetime 

history of all jobs (job title, activities, and exposure) of at 

least 6 months' duration . 

For childhood passive smoking exposure, we asked 

about the smoking habits (i .e ., amount and years of 

smoking) of father, mother, or other household members 

AtsREI'tAT1oNs USED : ADC- adenoeardnoena ; Q -eonfitlettce intenzl ; 

CSP-Univenity of Southern California/L,oc Angeles County Cancer 

Surveillance PTorram ; RRxrrlauve risk(s); SCCmtqtumous eell car• 

dnoma . 

tRereived June 11, 1984 ; revirrd Novembct 26 . 1984 ; «cepted 

December 11, 1984 . 

=5upported by grant S163 from the American Carscer Society . 

sDepartment of Family and Ptrverttive Medicine, Univenity of 

Southern Califomia School of Medicine, Parkview Medical Buildtna B, 

2025 Zonal Ave ., Laa Anaeles, CA 90031 . 

"Pruent addreu : Impetul Cancer Research Fund's Cancer Epide' 

mioloip Unit, Ra.dcliffe infirtnary, Oxford University, Oxford OX2 

6HE, Entland . 

s We thank the word•pro«uing pool for preparation of the manu . 

acip4 

747 JNC1 . VOL 74 . NO . 4. APiUL 1965

748 Wu, Hendet•son, P(ke, and Yu 

• when they lived with the respondent during her childhood 

and teenage years . For passive smoke exposure 

during adult life, we asked about the smoking habits of 

spouse(s) and other household members when they lived 

with the respondent . Passive smoke exposure at work was 

ass-essed only in terms of the average number of hours per 

day to which the respondent believed she was exposed at 

each job . 

The questions on vitamin A intake specifically asked 

about average frequencies of consumption of 21 vegetables 

and fruits that are high in S-carotene and 7 foods 

t.hat contained preformed vitamin A during the calendar 

year 3 years before diagnosis of the case (19) . Pattern of 

use of vitamin supplements was also assessed for the 

same period. On the basis of U .S Department of 

Agriculture tables of food values for standard portion size 

(common household measure) of each item (20), we 

estimated average daily intake of 0-carotene (or vitamin 

A) by summing the product of the 4-carotene (or 

vitamin A content of each food item and its reported 

frequency of consumption . Quartiles of consumption 

were constructed on the basis of the intake pattern of the 

220 controls . 

All cases were diagnosed microscopically . Their routine 

pathology reports were reviewed for mention of lung 

scarring . 

Statistical analysis was conducted with the use of 

multivariate logistic regression methods for individually 

matched case-control studies (21) . RR were estimated by 

odds ratios . A case-control pair was excluded from any 

given analysis if the information for either the case or the 

control was not known for the relevant variable(s) . Since 

personal smoking will often, if not always, confound 

other associations, RR for other factors were always given 

after adjustment was made for personal smoking . 

For ADC, RR for certain factors were given separately 

for nonsmokers, ex-smokers, and current smokers ; this 

was not done for SCC because the numbers of nonsmokers 

and ex-smokers were too few . 

RESULTS 

We interviewed 149 ADC and 71 SCC cases and their 

matched controls . The mean age at dfagrtosis was 59 .7 

Smoking status 

TAeLE 1 .-Pmwnal rnaokinp Aabite oJcaaex and coatrola 

years for ADC cases and 61,4 years for SCC cases . The 

mean ages (at date of diagnosis of the index case/ for the 

respective control groups were 59 .5 and 61 .1 yeais . 

Porsonal cigarette smoking .-For both ADC and SCC, 

there was a significant trend in risk associated with 

increasing number of cigarettes smoked per day and with 

decreasing age at which smoking began (table I) . Both 

aspects of smoking remained significant after adjustment 

was made for the other . 

Passive smoking .-Families tended to share similar 

smoking behavior . Controls whose father, mother. or 

spouse(s) smoked were more likely to smoke, to be heavN 

smokers, and to start at a younger age than controls 

whose family members did not smoke . For ADC and 

SCC, after adjustment was made for personal smoking 

habits, there were no significantly inaeased risks for 

having a mother, a father, or spouse(s) who smoked or fot 

being exposed at work (table 2) . 

For nonsmoking ADC cases, we did not observe an, 

elevated risk associated with passive smoke exposurt 

from either parents (RR=0 .6 ; 95% C1=0 .2, 1 .7), frorr 

spouse(s) (RR=1 .2; 95% C1=0.5, 3 .3), or at work 

(RR=l .3 ; 95% C1=0 .5, 3 .3) . Increasing RR (RR=1 .0 

1 .2, 2 .0) were found with increasing years (0, 1-S0, :t31 

of passive smoke exposure during adult life fron 

spouse(s) and at work, but the results were not sta 

tistically significant. Since the exposures may hav : 

occurred concurrently, the years of exposure rtpresen 

units rather than chronologic time of exposure . 

Childhood exposures .-For both ADC and SCC, nc 

significant association was found with history of luni 

diseases (specifinlly, asthma, bronchitis, pneumonia 

tuberculosis, fungal disrases, emphysema, and luni 

abscess) diagnosed by a physician at least 5 years befor 

diagnosis of the case . When the analysis was restricted v 

lung diseases that occurred before age 16 (childhood), ; 

significantly elevated RR for pneumonia was observe• 

for ADC after adjustment was made for personal smokin, 

habits (RR=2 .7 ; 95% CI=1 .1, 6 .7), and the RR for SC( 

(RR=2 .9 ; 95% C1=0 .5, 17 .4) was in the same directior 

Parental smoking did not explain this effect . Table 

shows that for ADC, the effect of childhood pneumoni 

was most apparent among nonsmokers : Of the 2 

ADC SCC 

RR 95% CI Cax/controi RR 95% Cl Casatcontrol 

Nonsmoker 1 .0 29/62 1 .0 2/30 

Ex-smoker" 1 .2 0 .6 . 2 .3 21/37 7 .7 0 .8, 70 .3 8/18 

,Eurrent smoker 4 .1` 2 .3 .7 .5 99/50 35 .3" 4,7 . 267 .3 61/23 

Current smoker : No. cit;arettes/day 

1-20 2 .7 1 .4 . 5 .4 38/28 17 .7 2 .3 . 138 .2 19/14 

?:21 6 .5" 3 .1, 13 .9 61/22 94 .4" 9 .9, 904 .6 42'9 ~ 

Current smoker : age started to smoke . yr . ~ 

225 1 .1 0,4 . 3 .2 8/14 7 .8 0 .8 . 73.7 6/5 ~~ 

19-24 2 .5 1 .0 . 5 .8 22/ 15 17 .1 4 .4 . 498 .5 18; 7 l~d 

Smoking status 

TAtLE 2-Erporurr to pasrive am.okiny in eaaa and eaatrol . 

ADC 

Adjusted RR' 95% CI 

Mother smoked 1 .7 0 .8 . 3 .5 

Father smoked 1 .b 0 .7, 2 .3 

Snousets) smoked' 1 .2 0 .6, 2 .5 

Exposure at the workplace 1 .2 0 .8, 22 

Lung Cancsr kt Woman 749 

SCC 

Adjusted RR' 95% CI 

0 .2 0 .0 . 1 .5 

0 .9 

0 .3 . 2_9 

1 .0 0 .1, 7 .6 

2 .3 0,7, 7 .9 

' Adjusted for number of ciaarettes smoked per day and age at starting to smoke . 

'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 . 

nonsmoking ADC cases, 8 (28%) gave a history of 

childhood pneumonia . 

Elevated RR, adjusted for personal smoking habits, 

were observed for exposure to burning coal used for 

heating or cooking in a stove or fireplace during the 

majority of childhood and teenage years (ADC : RR=2 .3 ; 

95% C1=1 .0, 5 .5 . SCC : RR=1 .9 ; 95% CI=0 .5, 6 .5). For 

ADC, elevated RR were observed in each personal 

smoking habit category (table 3) . 

TAei.E 3 .-RR and 95% cortftdnia interinL oJADC of the 

tung aecording to ehildhoad pneumania and ooal burninp by 

personal nnokinq habiti 

Exposure 

RR (95% CI) amone: 

Nonsmoker Ex-smoker Current smoker 

Childhood 

pniumonia' 

No 

Yes 

Childhood coal 

burnina' 

1 .0 

3 .1 (1 .0, 9 .9) 

1 .4 (0 .6, 2.4) 

1 .5 (02, 10 .8) 

5 .1 (2.5, 10 .3) 

10 .9 (2.1, 57 .9) 

No 

Yu 

1 .0 

32 (0.9 . 11.8) 

1 .6 (0.6 . 3.5) 

4 .3 (1 .0, 17 .8) 

6 .3 (8.0, 13 .3) 

91 (2.1 . 41 .9) 

' Before age 16 . The analysis was based on 149 csae-control pairs 

of ADC . 

'Includes heating or cooking with coal burned in a stove or 

fireplace during childhood and teenage years . The analysis was 

based on 143 cax-control pairs of ADC . 

Dietary vieamin A .-Table 4 presents RR for ADC, 

adjusted for personal smoking habits, by quartiles of 

indices of vitamin A consumption . Btcause of the smaller 

sample size of SCC cases, the indices were dichotomized . 

For ADC, a significantly inQeased risk was observed only 

for those in the lowest quartile of {3-earotene eonsumption 

(4,000 IU/day), but no appretiably increased 

risks were observed for those in the intermediate groups . 

For SCC, an elevated, but not statist .ically significant, RR 

was observed for women with 0-nrotene intake below 

the median : When those in the lowest quartile of Acnrotcne 

consumption, i .e ., less than 2,000 IU/day, were 

compared to those consuming more than 2,000 IU/day, 

the unadjusted RR was increased to 1 .7 (from 1 .3), but 

after adjustment the RR was not greater than comparisons 

above and below the median (both RR=1 .5) . 

There was no association with an index of total 

preformed vitamin A (i .e ., dairy products, eggt, liver, and 

vitamin supplements) for eithez cell type . However, for 

ADC and SCC, an association was observed for dairy 

products and eggs (table 4) . 

Other Jactors .-We could find no association between 

any occupation or occupational category and risk of ADC 

or SCC, but there was an excess number of cooks (4 cases 

and 2 controls) and beauticians (8 cases and 5 controls) 

among cases ; both occupations have been suggested in 

previous studies . Elevated RR adjusted for personal 

TAsI-e 4,-Dietary intake of S-r.nrotent, total prrJormed tltamin A, and dairy products and eppt amoxp eaau axd coatrots 

Qusrtile 

ADC 

1 (high) 1.0 1.0 1-0 

2 0.8 0 .E, 2.0 0.6 041.4 1.7 0 .8.8.9 

3 1.E 0 .6, 2.7 1.1 0.6, 2-E 2.2 1.014 .8 

4 2.6 1 .1,5.7 12 0.6,2.8 i.7 1t,6.8 

8CC 

1and2 1.0 1.0 1 .0 

8 and 4 1.5 0,6, E.8 1.0 0.4, 2.4 1.6 0.7, 8.9 

' lncludei 21 vegetables and fruits: leafy lettuce, other leafy rreen, broccoli, carrots, tomatoes, green peaa, green beant . lima beans, 

asparagus, summer squash, winter sqtush, sweet potatoes and/or yams, green pepper, red pepper, hot red chili pepper, cantiloupe, 

watermelon, peache., apricots, n.ctarines, and tomato and/or VS juice . Analysis was baaed on 147 pain of ADC and 69 pairs of SCC . 

`lncludes eggs, cheeaa butter and/ar margarine, cream, milk, beef and/or calf liver, chicken and/or tvrkey liver, and vitamin supplements . 

' Analyais was based on 147 pairs of ADC and 71 pairs of BCC, 

~ Adjusted for number of cigarettes smoked per day . 


p-Carotene' Total preformed vitamin A' Dairy products and s=trt' 

Adjustad RR' 95% Cl Adjusted RR` 96% CI Adjusted RRi Rilc CI 

JNU . VOL 74, NO. 4 . APRIL l9i5

TSO Wu, H .nd.rson, P1k ., and Yu 

smoking habits were observed for a history of hysterectomy 

(RR=1 .7 ; 95% C1=0 .9, 3 .2) and nullipariry 

(RR=1 .7 ; 95% CI=0 .8, 3 .7) among ADC cases and a 

history of miscarriage (RR=1 .5 ; 95% CI=0,5,4 .9) among 

SCC ases . 

Multiple logistic regression analysis was condutted to 

assess the possible confounding effects of personal 

smoking habits, childhood pneumonia, childhood coal 

burning, and S-arotene intake . The results were similar 

to those when each factor was adjusted for personal 

smoking habits alone . 

DISCUSSION 

This case-control study examined risk factors for the 

two main cell types of lung cancer in women-ADC and 

SCC . Although histologic typing was done by the 

individual pathologist at each participating hospital, 

studies comparing interobserver and intraobserver variability 

in classification of lung cell types reported a high 

concordance rate for cell types other than large cell 

carcinoma, which was excluded in this study (22, 23) . 

In this study population, about half of ADC and almost 

all of SCC can be attributed to personal smoking habits ; 

the amount smoked and the age at which smoking began 

were strong determinants of risk of disease . However, 

there are marked differences in the strength of association 

between smoking and cell type of lung cancer, as has 

been noted previously (24, 25) . 

The role of passive smoking in the etiology of ADC 

among nonsmokers is not clear . Our data are not 

consistent with the findings with regard to nonsmokers 

obtained by Hirayama (4) and Trichopoulos et al . (5) 

who reported a twofold to threefold increased risk due to 

passive smoking . However, the histology of the cases in 

these studies is not clear, and their data suggest that any 

effect of passive smoking is larger for SCC cases (5, 6) . Of 

our 29 nonsmoking ADC cases, 12 were bronchoalveolar 

cell carcinomas, and this cell type is specifically mentioned 

by Correa et al . (6) to have a weaker association 

with passive smoking . The effect of passive smoking by 

cell type of lung cancer needs to be investigated further in 

studies with much larger numbers of nonsmokers . 

Childhood lung disease may have a role in lung cancer 

etiology . Certain features of the lung of a child (e .g ., 

susceptibility to airway closure and high peripheral 

resistance) might make it more vulnerable to residual 

abnormalities from respiratory illness (26) . This notion 

is supported by observations that both smokers and 

nonsmokers with childhood respiratory diseases have 

impaired lung function capacity, that their rate of decline 

in ventilatory function capacity with age is more rapid 

than that in individuals without childhood respiratory 

problems, and that they have higher rates of clinical 

diagnosis of chronic obstructive pulmonary disease (27, 

28) . Women with childhood respiratory problems may 

have incurred epithelial damage to the airway resulting 

in airway hyperreactivity and are more susceptible to 

other insults to the lung . We cannot rule out the 

possibility of a chance finding or of preferential recall of 


childhood pneumonia by cases . However, our dat2 

appear to be internally consistent, since we found a 

significantly higher frequency of lung scarring mentioned 

in the pathology reports among cases with 

previous childhood pneumonia (12/30=40%) compared 

to those without (39/189=21%) . 

The associ.ation of lung cancer risk with exposure to 

coal heating or cooking warrants further investigationAlthough coal was identified as the major heating or 

cooking fuel used during childhood and teenage years of 

a significantly higher proportion of cases, we did not 

have detailed information on the years of use . Excess risks 

of lung cancer have been reported for coke oven workers 

(29, 30) and British gas workers (31) who were heavilN 

exposed to products of coal carbonization . 

Studies of men suggest that their lung cancer risk is 

lowered by greater dietary S-carotene (12-14, 32, 33 anc 

vitamin A intake (15, 17, 32, 33), but the evidence for 

women is less clear (12, 13, 32, 33) . We observed a 

significantly increased risk for ADC with the lowest leve ; 

of 4-carotene consumption and a similar association foi 

SCC . These results are consistent with findings fot 

females in Singapore (12) and in Japan (13), but they art 

not supportive of data for females in Hawaii (32) anc 

England (33) . Our observation of no association with ar 

index of total preformed vitamin A (i .e ., dairy producu 

eggs, liver, and vitamin supplements) and no associatior 

with total vitamin A intake (preformed vitamin A an( 

S-carotene-data not shown due to domination b, 

preformed vitamin A) is consistent with findings fo, 

females in Hawaii (32) . Conflicting findings have beer 

reported for subgroups of preformed vitamin A foods anc 

supplements . A higher consumption of liver and vitamir 

supplements has been reported previously for femal• 

cases as compared to controls, but the opposite result 

have been observed for males (33, 34) . Our data shor 

no ase-control difference in the intake pattern o 

vitamin supplements and a higher consumption of live 

among cases . Our finding of an elevated lung cancer ris 

associated with low levels of intake of dairy products ha 

not been reported for females, although similar result 

have been observed for males (15-17) . Our results on th 

role of /4-arotene and preformed vitamin A were simila 

for ADC and SCC, despite suggestions thai vitamin A (c 

rg-carotene) is more strongly protective against SCC tha 

against ADC (17) . 

Initial reports of an inverse relationship between bloo 

retinol levels and subsequent risk of cancer at all sites (3` 

36) have not been supported by recent studies (37, 38 

This situation emphasizes the need to reexamine even tt 

consistently observed association of vitamin A (or ~ 

carotene) intake with male lung cancer . 

Possible sources of bias in our data must be considerr. ~ 

Both lung cancer cases and controls were derived fro~ ~ 

population-based samples . However, because this disea ~; 

is debilitating and rapidly fatal, 190 patients had died ( (4 

were too ill to participate by the time of initial contac ~ 

We did not conduct proxy interviews because questiot ~ 

on childhood exposures and dietary history could not t 

assessed adeq uatel y . As ex pected , the grou p who was n ~ 

J Na, voL.'!1 . NO . 1. APRIL tll5 ' ' ~

,.' 

interviewed was murr likell to have metastatic disease at 

diagnosis but was similar in all demographic variables 

measured . In addititrtt, information abstracted from 

medical rti-cords showed similar smoking status for those 

intervicwed and those nt>t interviewed . If cases who were 

not interviewed bccause of poor survival differed from 

those who survived longer and were interviewed in terms 

of the other risk facturs under study, this could have 

biased our results . However, this appears unlikely since 

our data showed tha( histories of childhood pneumonia 

and exposure to coal fires were similar among cases 

regardless of stage of disease at diagnosis . There is also no 

evidence that cancer survival is associated with dietary 

vitamin A intake . 

The etiology of 5CC can be explained almost entirely 

bt cigarette smoking . Cigarette smoking, however, explains 

only about half of the ADC cases . On the basis of 

this study, childhood lung disease and exposure to coal 

fires in childhood explain at least another 22% of ADC 

cases . Passive smoking and vitamin A ma}• be involved, 

but more research is needed to clarify their roles in lung 

cancer etiolog} . 

REFERENCES 

(1) StU'ERaERG E Cancer sutisucs, 1982 . CA 1982, 32 :15-31, 

(?1 HEh'DERSOL' BE Descriptive cptdemology and geographic 

pathology . In : Burchenal JH . Oe+taen HF, eds . Cancer 

ach,evcrnenu- challense-s and prospecu (or the 1980 s 'Vol I . 

New York : Grune, 1981 :51-69 

l) 1 U .S . Public Health Service . The health conscquences of smoking 

Cancer . Washington fK: L' .S, Govt Print Off, 1982 [DHEW 

publication No . (PHSM2-50179) 

(4) HtR.AYAMA T . Non•smoking wives of heavy smokers have a higher 

risk of lung cancer: A study from Japan Br Med J 1981 ; 

282 :185-185 . 

(3) TatcHoroLLOs D, KALANDtD, A . SrARRoi L . MACMAHOn B 

Lung cancer and pauive smoking Int J Canca 1981 . 27 :1-4 

(6) CORREA P, PtCrcLE LW, Fon-ntAM E, LrN Y. HAENSUL W . Passive 

smoking and lung oncer, Lancet 1983 ; 2 :595-597 . 

(7) Xt' ZY, X1AO HP, Li G . Air pollution and lung cancer in 

Liaonrng Province . Nail Cancer Inst MonogT . In press 

(8) BRESt-oM' L, HoACUN L . RASSa,sscn G . AIRAMS HK Occupa• 

tions and cigarette smoking as risk faaon in lung cancer . Am J 

Public Health 1954 ; 44 :171-181 . 

(9) WYNDER EL,BESta JW .Cancerofthelungamongnon•smokeraspecial 

reference to histologic patterns . Cancer 1967 ; 

~ f.6:1161-1172. 

(1J) MErJCr HR, PI¢E MC, HENO[RSON BE, JtNG JS . Lung cancer risk 

1 among beautioaru and other fernak workers : drieJ communsration 

. J Natl Cancer Irut 1977t 59 :1423-1425 . 

1111 AutasACH 0, GAarrNVt L PAaas VR. Scu nrurr ol the lungirsaase 

over a 21 year period. Carscer 1979 ; 4l :656-642 . 

'(12) MACLENNAN R, DA COSTA J, DAY NE, LAMCH . Nc YK, SHAN . 

MucARATt+Aw K. Risk facton for lung cancer in Singapore 

Chine+e, a population with high female incidence rates . Int J 

Cancer 1977 ; 20 :854-864 

(13/ HIRAYAIAA T. Diet and cancer . Nuv CGncer 1979 ; 1 :67-81 . 

(le, SHExEttx RB, LErPER M, Liu S, etal . Dietary vitamin A and risk 


Lung Canc.r In Women 751 

of cancer in the Western Electric study Lanttr 1981 . 2 

1185-1190 

(13) B1ELS:E E . Dteun vlumin A and human lung cancer Int J Cancer 

1975, 15561-565 

(16) METTLrr. G .GRAHAM S .SkANSON M VlumtnAandlungcancer 

JNCI 1979 . 62,14l5-14S8 

(171 )t'ALL G . BIELKE E . GART JJ Dteury habtu and lung cancer risk 

Int J Cancer 1985, 51 :597-405 

(181 MAC.,, TM Cancer Surveillance Program in Los Angeles Counn 

Nail Cancer Inst Monogr 1977 ; 47 :99-101 . 

(19) GRAHAM S . MErruN C Fiber and other consutuenu of vegeubles 

in cancer eptdemtololp In Newell GR . Ellrson NM, eds 

Nutrition and cancer euoloin and treatment . New York . Raven 

Press . 1981 ;1 g9-215 

(20) ADAMS C. Nutriuvc value of American foods in common units 

L• .S Department of Agriculture Handbook No 456 Washtng~ 

ton . DC U .S Department of Agrtculture, 1975 

(21) BRESLOM NE, DAV NE . Suusual methods in oncer rrsearch 1'ol 

I-The analvsn of case-rontrol studies IARC Set Publ 1980, 

52 .5-558 

(22) YEs!.ER R GER57 B, Al'ERLACH O . Application Of the World 

Health Organtnuon classifiatton of lung carcinoma to biopsy 

material Ann Thorac Surg 1965 . I :D3-49 . 

(2I! YESNER R . CARTER D Patholo=y of carcinoma o( the lung Cltn 

Chest Med 1982 . 5 :257-289 

(24) DOLL R, HILL AB . KREYaERC L The significance of cell type in 

relauon to the aeuolog) of lung cancer, Br J Cancer 1957, 

11 45-48 

(25) WYNnER EL . CorEY L .S 

. MAancHl K Lung cancer in womenPresent and future trends, J Nail Cancer Inst 1973 . 551 :391-401 

(26) KArrAn M Long-term sequelae of resptruory illness in infancy 

and childhood, Pediatr Cltn North Am 1979, 26 :525-555 . 

(27) BuRRows B . KNUtxor. RJ, LEaowrTz MD . The relationships of 

childhood respiratory illness to adult obstructive airway disease 

Am Rev Respir Du 1977 ; 115 :751-759, 

(28) SAMCT JM . TACCa IB . Srctga FE. The relauonship bccween 

resp,raiory itlneas in childhood and chronic airflow obsvuction 

in adulthood Am Rcv Respir Dts 1983 . 127 :548-525, 

(29) REDMOND CK, ClOCCO A, LLOYD JW, RusH HW, Long-term 

mortality study of steel workers, VI . Mortality from mals6nant 

neoplasms among coke oven workers J Occup Med 1972, 

14 :621-629, 

(30) LLOVD JN' Long-term morulsty study of steelworkers V . 

Resptratory oncer in coke plant worken, J Occup Med 1971 ; 

15 :55-68 

(31) DoLt . R, FtsHER EJ, GAMwoN W, et al . Mortality of gvsworkers 

with special reference to dncen of the lung and bladder, chronic 

bronchitis, and pneumoconiosis Br J lnd Med 1965 ; 22 .1-12 . 

(32) HtNrx MVW . Kot.oNEL LN, HANRtN JH . Dseury viumin A, 

carotene, vitamin C and risk of lung cancer in Hawaii . Am J 

Epidemio) 1984 ; 119 .227-237 . 

(3)) GRECOR A, LEE PN . RoE FJ, W1LSON MJ . MELTON A. Compari• 

son of dseury histories in lung cancer tsses and controls with 

special reierence to vitamin A . Nuer Cancer 1980 ; 2 :95-97 . 

(3I) Ssarnt PG, Jrca H . Cancers among users of preparatiorts contain• 

ing vitamin A_ Cancer 1978 ; 42:806-811 . 

(i3) KAR . JD, SNrTH AH, SwrTZER BR, HAwES CC Serum vitamin A 

(rrtinol) and carscer irscidenae in Evaru County . C,eorgia . JNCI 

1981 ; 66 :7-16. 

(36) WALD N, IDLE M, BoREHAM J . Low serum vitamin A and subsequent 

risk of arscer, Lanca 1980 ; 2:813-815 . 

(37) Wsutrr WC, PoLk BF, UNDeaM'ooD BA, et al . Relarion of serum 

vitamin A and E and nrotenoids to the risk of cancer . N Engl J 

Med 1964, 510 :450-454 . 

(JF) STAHEUN HB, BUESS E . ROSEL F, WIDIitR LK, BRAIAUtER B . 

Vitamin A, cardiovascular risk factors, and mortality . Lancet 

1982, 1194-395 . 

JNCI . VOL 74 . NO 4, APRIL 1995


13

Wu-Williams, A .H ., Dai, X .D ., Blot, W ., Xu, Z .Y ., Sun, X .W ., Xiao, 

H .P ., Stone, B .J ., Yu, S .F ., Feng, Y .P ., Ershow, A .G ., Sun, J ., 

Fraumeni, J .F . and Henderson, B .E ., "Lung Cancer Among Women in 

North-East China," British Journal of Cancer 62 : 982-987, 1990 . 

A joint Chinese-American study of women in Shenyang and 

Harbin, two industrial cities in northeast China, reported that 228 

cases and 301 controls had been exposed to ETS in the workplace . 

A relative risk of 1 .1 (95% CI 0 .9-1 .6) was calculated, which the 

authors described as a "small excess risk," although it was not- 

statistically significant . The authors also noted that "there were 

no significant dose-response trends associated with years of 

passive smoke exposure at work ." 


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T+bk Vl hsu RFU ol lung noar usaeuted with tipe> ;1({ 

pnor chroruc lunt dtseases Lung dtseases that wen fsnt 

durosed within thrcc mn of )unl l.aoerr dsaptotts fand a 

eompanble urnr penod for controlst werz rscluded from Me 

anal)s•s After ao)usunl for smokin=, htstory of any pnor 

tunt dtseau was assocuted wtth a 5d5 . tncrqsed nsk I95M, 

Cl E1 The excess was /reates : for prseumonta (RA 

: ./) An Incrcascd nsk was (ound (or broochtas and,or 

emphvtema . but the assoctauon was hmned to sqwmous oat 

;tll caneen IRR 1 6) and nol found for adenocaranoma tRR 

09) 

v.e rnvesttjated whether risk of lung cancer varied aeeard• 

tn/ to the fal ume following the dtarnosts of pnor lung 

disease E.arlter drtetttoe of chrotuc bronchrtts•emphyxma 

conveyed rreatrr ntk Relauvt to those wrtlt no tusrory o( 

chrontc broncluus-emphysenu tAe RRs wers 1 .) . 1 .) . arsd 

I 1 respauvely for condtuons detecud 4- 10 . 11 -20, and 

:1 - vea .n brfort lung canm dta=rsosis On the othn hand . 

the FtRs wcrc hi/ner for more rseen( dtagnoses of prxumonu 

and TB T1x RRs wcrc :' ' 5 and I! respeetiveiy (or 

pnru .monia and '- 1 . 1 ), and 1 . : for TB fnt delected 4- 10 . 

11-20 and 2) + yean pnor lo lung aneer dtarnosu TTe 

tkvated nsk assocured with TB du3nox4 4-10 ye•an pnor 

to lung cancer was strntficant, it was obserred for both 

squxmous oat cell canarn and adenoarnnoma of the lunjand 

amon= non-smoken as well as smoken, 

Famil, 7rutort oJT® asd cancn 

we obsernd a stMhant 60' . (95',t CI 1 2-'s I i mertised 

nsk assocuted with TB tn a househo{d member, wttb simtiar 

nsks for squamous oat oell attcxn and adaooaraacvru 

The familial aswcunon wa.t sax m srnoken and rsoosmoken, 

and rrmamed unehanrrd after ad)usunl for 

personal history of TB TTe risk assonated w•Ith family history 

of TB mcrea,ised with decrrutn/ ar when the Indes 

subyect wu first expo+ed After ad)usttnl for smoking . 

exposures at are 30 cortfernd nsks of 

1 .7 . 1 .5 and 1 . : whea compared to tbase with no houxhob 

TB czposuls 

Famlly history of lung as+zr in 6nt dep .c rtiatins_ 

rrponed by 4 .5' . of the ases . wu usoeuted with a a¢uficant 

E0'. . (95•i. CI 1 .1-30) merusnj nsk TTM was ltttk 

dtf'iercecr tn nsk by cell type or erook,tnl status Tbe risk of 

lung eancrr was t.orne-whas hssher among thox witb a famtly 

htttory of other ancen tRR IA : 95% Ci 1 .0-2 .01 . wsth the 

esceu nsk bcinl hsther (or adenoearctaosiu (RR l .i) t3un 

for squa.mous .oat cell ancen (RR 1 .1) . 

.Nrrurnsa/ asd rtroaikrtf.r j.crnn 

Tabk Vlf pre+enu nats o(lua4 atncer by .atiow mensuual 

aad ttptoducuve f.ctott Tltre .ert littk or no assocveioa 

with aF at tnenarebe, parity . hrsursrtomy. tpontaateua 

abonion. prefnaxy rasah+z+t tn diffcult labau- assd we of 

oral contracrpuves There .vas a saPu5eant 30'i. (91v. Ct 

1 .2- 1 .1) snc7naed nsk asaoeiatad .ntb hissory ot mssa.rlude . 

asid ca.+es tandbd to bart a tater aF at natun .J saeoopatssac 

altbout.h the tretsd .ras wt sasooth 


Ll'NG CANCEa AMONG WOMEN IN CHINA eR! 

TMit Vll O eiauve nsks o( Iwy ta :cc aa.aeu .d ntk mrrauval anC 

reprodtcu .c facton 

Caafvrliv.rrr(s RR' 'I!% C1 

l~c ti nrnuene 

I/- It4t12 !0 

16 -1) 12' 412 1 1 101 . 1 41 

14-13 :15276 11101141 

. ) .7) SJ t3' Is 1 .f+ 

tub .rtvlo>tr 1034) 1 .3 10.9 . t .T) 33 1 .2 33 I ./ 

'AQ)sa•wd for yF . duesaoa . pr*>.a! *eottai aa6 sa.t1 ar .c'N..Ya af oan . .rsa 

faettw -Its% caa4se.ae tu .r.ah esdwrs ) A .

VGSTS 0GZOZ 


I

t aRected itnr4eErn famly memben wu small (e*,) R .anl 

caw -controi studtes in Grut Antssn (Ayexb .1 .1., 19}t) W 

the Un ted States (Caporuo er ril., 19/9), however, sugjtu 

that =enettc tra,u rnay mAuentt suaeepubt)tty tn a aueabk 

portlon of cases Tlsese tnvrsupuons r :v-mkd s,1nll>antly 

tncreused nsks of lung unar assxaud wtth the reruurully 

controlled abthty to extensively nuubohsc the dru[ debnso- 

Qutrx . a tratt aRmm[ S4'i of the convol population etudtc0 

in the L'nned Sutes 

we found no strong suppo*1 for a rok o(hormoeal f.non 

for lung cancer overall or spectfscsJh for adenocarcraorru 

The cases d d tend to rs.penenec menopause at 4ter Rtes. but 

the trend in nsk with age at menopause wu not smooth . 

Htstory of prolonged labour or hysterectomy, whseh had 

betin suspected as nsk (acton for adenoamnonu benuY of 

the potential for trauma•auoctated lung embolisrn . oaurnd 

more frequently among our cases, but the eXCess nsks wete 

aot u{nfieant smce reletively frr women were alfect .d Risk 

of lung cancrr was recrntly reponcd to be irscrezs .d aston[ 

Chtnese w&men ath alson nxnsvual cycle krsrth IGao r/ tl . . 

19bb1, but this vanable was not asxssed ia the eurrent Ftudy . 

In other countries thc nsk of lung canczr nrenenlly 

reduced amonl those with higher dKUry muke of 

carotenoids iZLelicr, 1999) but our 6ndmp are kaa ckar . 

Cases had sh=htly higher rather than lower intake of dark 

jreen leafN vegetables the most eommonly eonsumed rxh 

soura of carotene Moreover . in our arulysn uun[ a com• 

btned rndcs of all vt[etables nch in nrotene, high (rcquen- 

Rei.r..ea 


AYESH, R . IDLE . 1 . RtTCHIE. I C . . CROTIiERS . MJ t HETZEL M R 

119tai Mrubolic oe1aauan plxnocrpes au nurkan for atarsp 

nbtlny to lunt canar v .rar 31L 169 

ptf.SLOW !+E A DAY . yE (11f01 Srorunrd MnAeLt w Cwrn 

RruarrA rAr .Inaltiu of Cau-Conrrs/ Srrkcs IARC Lyon 

CArORA54 !+E . FALK . RT . ISIAQ HJ t S orhers (Ift1) Lung 

tana+ nak . oaupauonal ezposure . Oebnfoqwre meubdrc 

phenotypt Car,rn Rn . 0 . 3675 . 

CHAn . w C COLIUOR!.E M 1 . FUNG, S C ! MO H C (117q1 

Ironcn,al anctt tn Honi Kon{ 1976- 1917 . I• J Cwrn . ?t . 

Iil 

COHE'v 11 . DIAMOND E L, GRAVE3 C.G l 1 othm 119771 A 

common familul component in lung oxer and ehroe+c okatrvc• 

tuve pulmonan dirrue la .rrr . IL 523 

ERSHOw A G t CHEN w K (1/9t)1 Chtn .c foa4 eornpo .oos 

ubks a tranatauon with EnllisA Common nama Ltun rawnvEe 

namaa and hnytn rortunu.d u%a .6urar»s_ fr/ C.q A.r' . 

(te the preu) 

GAO YT . ILCrT . wJ . ZHEhrG w a S ert.ers (IN7). Lwy aaW 

amon/ Chirxsc womrn f∎t J Cwrn . 4{ . iW 

GAO1' T . ILOT, w 1 .. ZHEHG, w_ 1TL.MUMEM. 1 F • HSU 

.aa{fa, Av, J. [{~fr . C w(Ittll Lun= ctanr ted veokia[ u Sh...f 

.. 

11 . :71 

HINDS -4 W .4TEMMERMAKH .O .N . . YANG . H .Y a ) 9elan (IMI) . 

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ets exposure, lung cancer - Legacy Tobacco Documents Library

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