Lack of effect modification between estrogen metabolism genotypes and combined hormone replacement therapy in postmenopausal breast cancer risk.

摘要

Postmenopausal use of combined hormone replacement therapy (CHRT) containing both estrogens and progestins has been associated with increased breast cancer risk (1, 2). There is also evidence that genetic variants in candidate estrogen metabolism genes influence the disposition of exogenous estrogen. The genes involved in the disposition of estrogen are well known, and include catechol-O-methyltransferase (COMT), the sulfotransferases SULT1A1 and SULT1E1, and members of the cytochrome P50 family including CYP1B1, CYPIA2, and CYP1A1. Functionally relevant genetic variants exist in each of these genes. However, it remains unclear whether these genes affect breast cancer risk (3-10), and there is even less information about whether these genes interact with relevant exposures to influence breast cancer etiology. Therefore, we evaluated whether there was evidence for modification of the effect of CHRT use by genes involved in the downstream metabolism of estrogens including COMT, CYP1A1, CYP1A2, CYP1B1, SULT1A1, and SULT1E1.