Polymorphic catechol-O-methyltransferase gene and breast cancer risk

We examined 483 Finnish breast cancer cases and 482 population controls to determine the potential effect of catechol-O-methyltransferase (COMT) genot ype in individual susceptibility to breast cancer, Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by unconditional logistic regre ssion after adjustment for known or suspected risk factors for breast cante r. When studied separately by menopausal status, the COMT-L allele-containi ng genotypes were inversely associated with premenopausal breast cancer, es pecially with advanced stage of the disease (OR, 0.44; 95% CI, 0.22-0.87). Among postmenopausal women a similar decreased risk was seen for local carc inoma associated with the COMT-LL genotype (OR, 0.55; 95% CI, 0.31-0.98). T he lowest breast cancer risk was seen in the postmenopausal women with the COMT-LL genotype and low body-mass index (less than or equal to 25.4 kg/m(2 ); OR, 0.33; 95% CI, 0.13-0.83). Significantly increased risk, on the other hand, was seen for postmenopausal women with the COMT-LL genotype and long -term (> 30 months) use of estrogen (OR, 4.02; 95% CI, 1.13-14.3), or with the COMT-L allele-containing genotypes and early age (less than or equal to 12 years) at menarche (OR, 8.59; 95% CI, 1.85-39.8). Our study, therefore, suggests that the COMT genotype may define a portion of the individual bre ast cancer susceptibility that is associated with reproductive events and h ormone exposure even if it does not seem to be a major overall risk factor for this malignancy.