Estrogen exposure during postmenopausal, reproductive, early childhood and even during the intra-uterine period may play roles in the development of breast cancer in women. The goal of this proposal is to examine whether polymorphic variants of genes that control the biosynthesis, cellular binding and metabolism of endogenous estrogen (CYP17, CYP19, ER, CYP1A1, CYP1B1, and COMT) are associated with breast cancer. All prior studies examining this hypothesis used a classical case-control design which is susceptible to population stratification bias and produced inconsistent results. We propose to use a family-based design which is free from such biases to examine this hypothesis among 3,0671 eligible nuclear families (with 5,916 family members) participating in the six international CFRBCS centers. All subjects will be genotyped for the proposed estrogen-gene variants using high-throughput laboratory methods (i.e., TaqMan and molecular beacon methods) which have been validated and are up-and running in our laboratories. Associations between estrogen-related gene variants using high-throughput laboratory methods (i.e., TaqMan and molecular beacon methods) which have been validated and are up and running in our laboratories. Associations between estrogen-related gene variants and breast cancer will be assessed by new analytic methods for family-based genetic association studies which we have developed. By virtue of the family based design, the proposed study will be able to assess, in an unbiased fashion, the impact of a woman's own as well as her mother's estrogen gene status on the development of her breast cancer. Findings of the study will be relevant for breast cancer prevention among women who may be inherently susceptible to the effect of estrogen-the key element in breast cancer etiology.
Showing the most recent 10 out of 81 publications
