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

Breast Cancer Res Treat. 2009 Jul;116(1):195-200. doi: 10.1007/s10549-008-0121-3. Epub 2008 Jul 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Ataxia Telangiectasia Mutated Proteins
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Cell Cycle Proteins / genetics
  • DNA Methylation / genetics*
  • DNA-Binding Proteins / genetics
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation
  • Humans
  • Israel
  • Middle Aged
  • Ovarian Neoplasms / ethnology
  • Ovarian Neoplasms / genetics*
  • Promoter Regions, Genetic / genetics*
  • Protein-Serine-Threonine Kinases / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Proteins / genetics


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • ATM protein, human
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases