Tobacco and Public Health - TCSC Indonesia

540
ENDOMETRIAL CANCER
Comments
The results of at least 26 epidemiological studies to date suggest that current or recent
smoking is associated with a small to moderate decreased risk of endometrial cancer,
particularly among postmenopausal women who smoked for many years at high
intensity. Associations between cigarette smoking and increased risk of osteoporosis
(Baron 1984; Jensen et al. 1985; Jensen and Christiansen 1988; Baron et al. 1990), and
attenuated effects of HRT among smokers (Jensen and Christiansen 1988), suggest an
‘antiestrogenic’ effect of smoking (Baron 1984; Baron et al. 1990). However, circulating
levels of estrogen generally do not differ according to categories of cigarette smoking.
A positive association between smoking and blood androgen levels has been observed
consistently, especially with androstenedione, although its relevance to the association
between smoking and endometrial cancer risk remains unclear.
Regarding the effects of smoking on estrogenic profiles, the type, rather than the
absolute levels, of circulating estrogens may be important. In particular, smoking may
increase estradiol 2-hydroxylation, which has been observed to decrease mammary
epithelial proliferation rates in experimental studies (Bradlow et al. 1996). Although
active smokers and nonsmokers may have the same concentrations of estrogens overall,
smokers might have a lower concentration of more biologically active estrogens
(primarily 16-alpha-hydroxyestrone). However, only one study (Michnovicz et al.
1986) has directly examined 2-hydroxylation in relation to cigarette smoking, finding a
50 per cent increased estradiol 2-hydroxylation in premenopausal women who smoked
at least 15 cigarettes per day compared to nonsmokers. Although based on relatively
small sample sizes, the findings of lowered levels of urinary estriol, and increased
urinary 2-OEH1, among smokers observed in two studies (Michnovicz et al. 1988;
Berstein et al. 2000) may support the hypothesis that smoking decreases the formation
of active estrogen metabolites along the 16-alpha-hydroxylation pathway.
Since adipose tissue is the main determinant of estrogen levels among
postmenopausal women, and is inversely associated with smoking, BMI may partly
mediate the inverse association between cigarette smoking and estrogen. Most studies
have adjusted for current BMI, although more relevant measures may include changes
in body weight over time, waist-to-hip ratio, or duration of obesity. In addition, smoking
appears to lower the age at which women reach menopause by an average of about
1–1.5 years, an association that seems to weaken with time since smoking cessation.
Statistical adjustment for the effects of age at menopause generally has not altered the
inverse associations between smoking and endometrial cancer risk. While a lower
average body weight and earlier age at menopause among current smokers compared
to nonsmokers certainly mediates some of the inverse association between smoking
and endometrial cancer risk, the extent of this mediation remains unclear.
Effect- modification may provide clues to the mechanisms underlying associations
observed in epidemiological studies. However, the data regarding effect modification