Estrogen metabolism and exposure in a genotypic-phenotypic model for breast cancer risk prediction.

ABSTRACT:

Background

Current models of breast cancer risk prediction do not directly reflect mammary estrogen metabolism or genetic variability in exposure to carcinogenic estrogen metabolites.

Methods

We developed a model that simulates the kinetic effect of genetic variants of the enzymes CYP1A1, CYP1B1, and COMT on the production of the main carcinogenic estrogen metabolite, 4-hydroxyestradiol (4-OHE(2)), expressed as area under the curve metric (4-OHE(2)-AUC). The model also incorporates phenotypic factors (age, body mass index, hormone replacement therapy, oral contraceptives, and family history), which plausibly influence estrogen metabolism and the production of 4-OHE(2). We applied the model to two independent, population-based breast cancer case-control groups, the German GEN

SUBMITTER: Crooke PS 

PROVIDER: S-EPMC3472969 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature