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    Breast Cancer Res Treat. 2009 Jul;116(1):195-200. Epub 2008 Jul 19.

    Promoter methylation patterns of ATM, ATR, BRCA1, BRCA2 and p53 as putative cancer risk modifiers in Jewish BRCA1/BRCA2 mutation carriers.

    Kontorovich T, Cohen Y, Nir U, Friedman E.

    Source

    The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, The Chaim Sheba medical Center, Tel-Hashomer, Israel.

    Abstract

    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.

    PMID:
    18642075
    [PubMed - indexed for MEDLINE]

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