As part of functional genomic studies following up a case-control genome-wide association study (GWAS) performed with the large and influential National Surgical Adjuvant Breast and Bowel Project P-1 and P-2 SERM breast cancer prevention trials, we investigated the top GWAS SNPs in CTSO gene on chromosome 4 and mechanisms of CTSO involvement in the regulation of BRCA1 and response to therapy. Here, BRCA1 is linked to breast cancer.