Tobacco and Public Health - TCSC Indonesia

He further noted that case–control studies relying on population controls, or on
controls with diseases unrelated to smoking, pointed to a weak positive association, as
did cohort studies in which selection bias is unlikely.
An additional refinement in epidemiological studies was introduced when the
possibility was raised that passive smoking may increase the risk of breast cancer
(Morabia et al. 1996). Non-smokers were subdivided into those genuinely nonexposed
to tobacco smoking (that is non-smokers that have not been passively exposed
to tobacco smoke) and those passively exposed to environmental tobacco smoke. In an
exhaustive and thoughtful review, Morabia (2002) identified 11 case–control studies
that evaluated active smoking in relation to breast cancer using as referent women who
were not exposed to either active or passive smoking. In all of these studies, the point
estimate of the adjusted odds ratio for breast cancer among active smokers was higher
than the null value of 1 and in six of them the relative risk elevation was statistically
significant. However, the results of a recent large cohort study, in which passive smokers
were excluded from the non-smoking referent group, were less clearcut (Egan et al.
2002); the relative risk (and 95 per cent confidence interval (CI)) for breast cancer was
1.04 (0.94–1.15) among current active smokers and 1.09 (1.00–1.18) among past active
smokers.
The results of case–control studies may have been biased because exposure histories
were collected after disease onset, and health conscious women, who are generally
non-smokers, may have been over-represented among controls. Indeed, there is some
evidence, discussed later on, that points to information bias in case–control studies.
On the other hand, the fact that smokers have, as a rule, an earlier age at menopause
(Cooper et al. 1999) which is associated with lower breast cancer risk (Hankinson and
Hunter 2002), tends to introduce negative confounding that has not always been
accounted for. It should also be noted that in perhaps the most powerful epidemiological
study (Egan et al. 2002), a significant increase in breast cancer risk was found, as
predicted, among women who begun smoking before the age of 17 years (RR = 1.19,
95 per cent CI 1.03–1.37). The results of another study have pointed to the same direction
(Innes and Byers 2001). In addition, findings indicating that cigarette smoking may
modify the prevalence and spectrum of p53 mutations in breast tumours (Conway et al.
2002), evidence that smoking may selectively increase breast cancer risk in high-risk families
(Couch et al. 2001), and reports that smoking is associated with an increased occurrence
of hormone receptor negative tumours (Morabia et al. 1998; Manjer et al. 2001)
cannot be explained on the basis of simple forms of information and selection bias.
Epidemiological evidence on passive smoking
and breast cancer
DIMITRIOS TRICHOPOULOS AND ARETI LAGIOU 505
The fact that passive smoking was found to be a significant predictor of coronary heart
disease among non-smoking women in the Nurses’ Health Study (Kawachi et al. 1997),