Breast Cancer Research and Treatment

, Volume 116, Issue 1, pp 195–200 | Cite as

Promoter methylation patterns of ATM, ATR, BRCA1, BRCA2 and P53 as putative cancer risk modifiers in Jewish BRCA1/BRCA2 mutation carriers

  • Tair Kontorovich
  • Yoram Cohen
  • Uri Nir
  • Eitan Friedman


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.


Methylation BRCA1 BRCA2 Modifier genes Cancer susceptibility Epigenetic mechanisms 


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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Tair Kontorovich
    • 1
    • 2
  • Yoram Cohen
    • 3
  • Uri Nir
    • 2
  • Eitan Friedman
    • 1
    • 4
  1. 1.The Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human GeneticsThe Chaim Sheba medical CenterTel-HashomerIsrael
  2. 2.The Mina and Everard Goodman Faculty of Life SciencesBar-Ilan UniversityRamat GanIsrael
  3. 3.The Gyneco-Oncology DepartmentThe Chaim Sheba medical CenterTel-HashomerIsrael
  4. 4.The Sackler School of MedicineTel-Aviv UniversityRamat AvivIsrael

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