Methylation of BRCA1 and MGMT genes in white blood cells are transmitted from mothers to daughters

Background: Constitutive methylation of tumor suppressor genes are associated with increased cancer risk. However, to date, the question of epimutational transmission of these genes remains uniesolved. Here, we studied the potential transmission of BRCA1 and MGMT piomoter methylations in mother-newborn pairs. Methods: A total of 1014 female subjects (cancel-free women, n = 268; delivering women, n = 295; newborn females, n = 302; breast cancer patients, n = 67; ovarian cancer patients, n = 82) were screened for methylation status in white blood cells (WBC) using methylation specific PCR and bisulfite pyrosequencing assays. In addition, BRCA1 gene expression levels weie analyzed by quantitative real-time PCR. Results: We found similar methylation frequencies in newborn and adults for both BRCA1 (9.9 and 9.3%) and MGMT (12.3 and 13.1%). Of the 290 mother-newborn pairs analyzed for promoter methylation, 20 mothers were found to be positive for BRCA1 and 29 for MGMT. Four mother-newborn pans were positive foi methylated BRCA1 (20%) and rune pairs were positive for methylated MGMT (31%). Intriguingly, the delivering women had 26% lower BRCA1 and MGMT methylation frequencies than those of the cancer-free female subjects. BRCA1 was downregulated in both cancer-free woman carrieis and breast cancer patients but not in newborn carriers. There was a statistically significant association between the MGMT promoter methylation and late-onset breast cancers. Conclusions: Our study demonstrates that BRCA1 and MGMT epimutations are present fiom the early life of the carriers. We show the transmission of BRCA1 and MGMT epimutations from mother to daughter. Our data also point at the possible demethylation of BRCA1 and MGMT during pregnancy.