Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk

Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of estrogen catechols, In a case-control study, we evaluated the association of the low-activity allele (COMTMet) viith breast cancer risk. Compared to women with COMTVal/Val, COMTMet/Met was associated with an increased risk among premenopausal women [odds ratio (OR), 2.1; confidence interval (CI), 1.4-4.3] but was inversely associated with postmenopausal risk (OR, 0.4; CI, 0.2-0.7). The association of risk with at least one low-activity COMTMet allele was strongest among the heaviest premenopausal a omen (OR, 5.7; CI, 1.1-30.1) and among the leanest postmenopausal women (OR, 0.3; CI, 0.1-0.7), suggesting that COMT, mediated by body mass index, may be playing differential roles in human breast carcinogenesis, dependent upon menopausal status.