BRCA1 promoter methylation in peripheral blood cells is associated with increased risk of breast cancer with BRCA1 promoter methylation

BRCA1 promoter methylation reportedly plays an important part in the pathogenesis of human breast cancer. In the present study, we investigated whether or not BRCA1 promoter methylation in peripheral blood cells (PBCs) can serve as a risk factor for developing breast cancer. The association of BRCA1 promoter methylation in PBCs with breast cancer risk was examined in a case–control study (200 breast cancer patients and 200 controls). BRCA1 promoter methylation in PBCs and breast tumors was determined with a methylation-specific quantitative PCR assay. BRCA1 promoter methylation in PBCs was seen in 43 (21.5%) of the breast cancer patients and in 27 (13.5%) of the controls. The odds ratio for breast cancer adjusted for other epidemiological risk factors was 1.73 (1.01–2.96) and was statistically significant (P = 0.045). When breast tumors were classified into those with and without BRCA1 promoter methylation, the odds ratio was 0.84 (0.43–1.64) (P = 0.61) for BRCA1 promoter methylation-negative and 17.78 (6.71–47.13) (P < 0.001) for BRCA1 promoter methylation-positive breast tumors. BRCA1 promoter methylation in PBCs is significantly associated with risk of breast cancer with BRCA1 promoter methylation. This seems to indicate that BRCA1 promoter methylation in PBCs may constitute a novel risk factor for breast cancer with BRCA1 promoter methylation.