Breast cancer chemoprevention pharmacogenomics: Deep sequencing and functional genomics of the and genes.

Our previous GWAS using samples from the NSABP P-1 and P-2 selective estrogen receptor modulator (SERM) breast cancer prevention trials identified SNPs in and near that were associated with breast cancer risk during SERM chemoprevention. We have now performed Next Generation DNA sequencing to identify additional SNPs that might contribute to breast cancer risk and to extend our observation that SNPs located hundreds of bp from estrogen response elements (EREs) can alter estrogen receptor alpha (ERα) binding in a SERM-dependent fashion. Our study utilized a nested case-control cohort selected from patients enrolled in the original GWAS, with 199 cases who developed breast cancer during SERM therapy and 201 matched controls who did not. We resequenced approximately 500 kb across both and , followed by functional genomic studies. We identified 4079 SNPs across and 3876 across , with 9 SNPs in and 12 in with