Functional genomic studies demonstrated SNP-dependent estradiol (E2) induction of the expression of both ZNF423 and CTSO and, downstream, of BRCA1, offering a mechanistic explanation related to the role of BRCA1 in DNA double strand break repair for the association of these SNPs with risk for breast cancer during SERM therapy.6 Alteration in the regulation of BRCA1 might be expected to influence carcinogenesis for ER-positive tumors as well as ER-negative breast cancers. The gene discussed is CTSO; the disease is breast carcinoma.