Tobacco and Public Health - TCSC Indonesia

attenuated in every study after controlling for potential confounders, including diet
and alcohol in many of the studies.
The presence of an association is incontrovertible, suggesting that this association is
causal, or represents a consistent bias or uncontrolled confounding. Arguing against
confounding is the consistency of the findings in males and females in diverse populations,
including the US, Norway, France, and Japan, the strength of the association, and
the dose–response pattern for intensity and duration of smoking, and the similar
results for age-adjusted and multivariate analyses (Hill 1965). A second possibility is
that the results were due to some consistent bias. Of note, most studies were based on
endoscopied individuals, it is plausible that smokers are more likely to undergo
endoscopy for indications related to an underlying polyp as compared with nonsmokers,
creating a bias whereby smokers with adenomas would be preferentially
entered into the study population. However, even in studies or sub-groups in which all
in the defined population are screened regardless of symptoms (Hoff et al. 1987;
Demers et al. 1988; Monnet et al. 1991; Zahm et al. 1991; Honjo et al. 1992; Giovannucci
et al. 1994a, b), smokers are at higher risk. Another possibility is that adenomas might
be more easily detectable during endoscopy for smokers, perhaps because of a relaxing
effect of nicotine on the large bowel. However, this bias is more plausible for small
adenomas but less so for large adenomas (Zahm et al. 1991; Honjo et al. 1992; Kune
et al. 1992b; Lee et al. 1993; Giovannucci et al. 1994a, b; Jacobson et al. 1994; Boutron
et al. 1995; Longnecker et al. 1996; Terry and Neugut 1998; Nagata et al. 1999; Potter et al.
1999); moreover, associations have been observed consistently in past smokers, where
the putative relaxing influence of nicotine would no longer be present.
Smoking and colorectal cancer
EDWARD GIOVANNUCCI 447
Summary of studies in the United States
In general, the early studies on tobacco and colorectal cancer did not support an association
(Hammond and Horn 1958, 1966; Higginson 1966; Kahn 1966; Staszewski
1969; Weir and Dunn 1970; Doll and Peto 1976; Williams and Horm 1977; Graham et al.
1978; Doll et al. 1980; Haenszel et al. 1980; Rogot and Murray 1980). For example, in
the earliest report based on data from the Veterans Administration by Hammond and
Horn, 187 783, men were followed from 1952 to 1955 and accrued 667 753 personyears
(Hammond and Horn 1958). Compared to never smokers, cigarette smokers had
a twofold excess risk of all cancers combined but not for cancers of the colon (84 cases
observed, 108.4 expected) or rectum (55 observed, 58.8 expected). Following publication
of data suggesting a 35 to 40-year induction period between smoking and risk for
colorectal cancer (Giovannucci et al. 1994a, b), Heineman et al. (1994) further studied
the Veterans Administration population for the period covering 1954–1980. In this
new analysis, based on 3812 colon cancer deaths and 1100 rectal cancer deaths, risk
increased with earlier age of initiating smoking (about a 40–50% increase for both