ACA BRCA1 promoter polymorphism genotypic frequency among unaffected individuals and breast disease patients

We previously identified a +ACA polymorphism at ‐600 bp in the BRCA1 promoter that creates a FAC1 transcriptional repressor binding site. Subsequently, we performed a genotyping study to determine the prevalence of this BRCA1 promoter polymorphism among unaffected individuals and patients with breast disease. The genotypic distribution of the BRCA1 promoter was determined for 997 unaffected individuals and 763 patients with breast disease from the Mayo Clinic, UNC Hospitals, and the Carolina Breast Cancer Study. The BRCA1 promoter genotypic frequency among unaffected individuals was 481/997 (48%) WT/WT, 432/997 (43%) WT/ACA, and 91/997 (9%) ACA/ACA. The BRCA1 promoter genotypic frequency among patients with breast disease was 348/763 (46%) WT/WT, 343/763 (45%) WT/ACA, and 72/763 (9%) ACA/ACA. No differences were noted in the genotypic distribution of the BRCA1 promoter among patients with DCIS, BRCA1 mutation, suspected BRCA1‐related cancer (BRCAx), or sporadic breast cancer. The allelic frequency of the +ACA BRCA1 promoter polymorphism among breast disease groups [343/415 (83%) WT/ACA and 72/415 (17%) ACA/ACA] were not different than the allelic frequency of the controls [432/523 (83%) WT/ACA and 91/523 (17%) ACA/ACA]. Our results suggest that the +ACA BRCA1 promoter polymorphism occurs commonly, and may contribute to breast cancer upon activation of the FAC1 repressor protein. Support: NIH CA78343.