Tobacco and Public Health - TCSC Indonesia

514
SMOKING AND OVARIAN CANCER
appears to be related to increased levels of adrenal androgens. In premenopausal
women, smoking increases the androgen–estrogen ratio of follicular fluid (Van
Voorhis et al. 1992), to which the ovarian epithelium is exposed. It seems reasonable
that smoking could thus act on the ovarian epithelium through hormonal effects, but
more studies are needed.
Tobacco smoking and risk of ovarian cancer
Several mechanisms support the biologic plausibility of an association between
tobacco smoking and ovarian cancer, however given the above discussion, it is uncertain
in which direction, to increase or decrease risk, the association should be. Results
from early studies evaluating the association between cigarette smoking and risk of
ovarian cancer lead IARC in 1987 to report that ovarian cancer was not considered to
be a tobacco-related cancer (IARC 1987). With the exception of a British cohort study
(Doll et al. 1980), no association has been found between tobacco smoking and risk of
ovarian cancer in subsequent prospective studies (Engeland et al. 1996), and additional
case–control studies have found null or inconsistent results (Trichopoulos et al. 1981;
Smith et al. 1984; Tzonou et al. 1984; Baron et al. 1986; Franks et al. 1987; Hartge et al.
1989; Franceschi et al. 1991; Polychronopoulou et al. 1993). Some studies have
observed nonsignificant reductions in risk among smokers (Byers et al. 1983;
La Vecchia et al. 1984). In a Japanese case–control study of alcohol consumption and
risk of breast, corpus uteri, and ovarian cancer, Kato et al. (1989) found a nonsignificant
relative risk of 0.78 (95% CI: 0.56–1.08) for ever smokers versus never smokers.
Evaluating several reproductive, dietary, genetic, or environmental factors on the
development of ovarian cancer, studies by Whittemore et al. (1988), Mori et al. (1988),
and Slattery et al. (1989) reported no significant differences in tobacco use between
cases and controls, though no details were given. An increase in ovarian cancer
risk associated with tobacco smoking has also been observed (Cramer et al. 1984;
Stockwell and Lyman 1987). Cramer et al. (1984) conducted a population-based
case–control study of dietary factors and ovarian cancer that found a nonsignificant
increased relative risk of 1.8 (95% CI: 0.54–5.97) for smokers versus nonsmokers.
Those authors found no significant trends in risk in relation to lifetime pack-years
of cigarette smoking (Cramer et al. 1984). Several of the studies (Cramer et al. 1984;
Mori et al. 1988; Slattery et al. 1989; Polychronopoulou et al. 1993) did not control for all
of the most potentially important confounding factors including age, parity, and oral
contraceptive use, and this is a limitation in considering their results.
Risk differences according to histologic subtype
There is evidence that various risk factors involved in the development of epithelial
ovarian cancer—including parity and oral contraceptive use—might vary by the histologic
type of the tumor (Risch et al. 1996). Germline BRCA1 or BRCA2 mutations do not
occur in women with mucinous tumors (Risch et al. 2001). A follow-up study of more