Polymorphic catechol-O-methyltransferase gene, duration of estrogen exposure, and breast cancer risk: A nested case–control study in Taiwan

Background: Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens, which are hypothesized to participate in estrogen-induced carcinogenesis. Methods: We examined 87 cases and 341 population controls in Taiwan to determine the association between the functional genetic Val158Met polymorphism in membrane-bound form of COMT gene and female breast cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by conditional logistic regression. Results: There was no overall association between COMT genotype and individual susceptibility to breast cancer. However, COMT-L variant genotypes appear to pose increased risk of breast cancer in women with greater duration from menarche to first full-term pregnancy (>8 years) (OR, 2.67; 95% CI, 1.00–7.36). Conclusions: This study based on limited sample sizes suggests that there may be no overall association of COMT genotype with breast cancer, but the COMT-L allele could pose enhanced risk of breast cancer in the presence of relevant environmental exposures, as most low penetrance gene are expected to act through gene–environment interactions.