Promoter methylation patterns of ATM, ATR, BRCA1, BRCA2 and P53 as putative cancer risk modifiers in Jewish BRCA1/BRCA2 mutation carriers
BRCA1/BRCA2 germline mutations substantially increase breast and ovarian cancer risk, yet penetrance is incomplete. We hypothesized that germline epigenetic gene silencing may affect mutant BRCA1/2 penetrance. To test this notion, we determined the methylation status, using methylation-specific quantitative PCR of the promoter in putative modifier genes: BRCA1, BRCA2, ATM, ATR and P53 in Jewish BRCA1/BRCA2 mutation carriers with (n = 41) or without (n = 48) breast cancer, in sporadic breast cancer (n = 52), and healthy controls (n = 89). Promoter hypermethylation was detected only in the BRCA1 promotor in 5.6–7.3% in each of the four subsets of participants, regardless of health and BRCA1/2 status.Germline promoter hypermethylation in the BRCA1 gene can be detected in about 5% of the female Israeli Jewish population, regardless of the BRCA1/2 status. The significance of this observation is yet to be determined.
KeywordsMethylation BRCA1 BRCA2 Modifier genes Cancer susceptibility Epigenetic mechanisms
- 6.Wylie B, Melissa AA (2002) Genetic risk in context: calculating the penetrance of BRCA1 and BRCA2 mutations. J Natl Cancer Inst 94:1185–1187Google Scholar
- 26.Kang JH, Kim SJ, Noh D, Park IA, Choe KJ, Yoo OJ, Kang H (2001) Methylation in the p53 promoter is a supplementary route to breast carcinogenesis: correlation between CpG methylation in the p53 promoter and the mutation of the p53 gene in the progression from ductal carcinoma in situ to invasive ductal carcinoma. Lab Invest 81:573–579PubMedGoogle Scholar