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Breast Cancer Research and Treatment

, Volume 136, Issue 3, pp 869–874 | Cite as

Germline mutations in RAD51C in Jewish high cancer risk families

  • Anya Kushnir
  • Yael Laitman
  • Shani Paluch Shimon
  • Raanan Berger
  • Eitan FriedmanEmail author
Epidemiology

Abstract

Germline mutations in BRCA1 and BRCA2 account for ~30 % of inherited breast cancer. RAD51C was reported as an additional breast/ovarian cancer susceptibility gene in some populations. There is a paucity of data on the putative contribution of this gene to inherited breast/ovarian cancer in Jewish high risk families. High risk Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1 or BRCA2, were screened for RAD51C germline mutations by direct sequencing of exons and flanking intronic sequences. Overall, 206 high risk women, 79 (38.3 %) of Ashkenazi origin, were genotyped for RAD51C mutations: 190 (92.3 %) with uni- or bilateral breast cancer (mean age at diagnosis 51.3 ± 11.1 years), 14 with ovarian cancer (mean age at diagnosis 55.6 ± 8.7 years), and two with both breast and ovarian cancer. No truncating mutations were noted, and two previously described missense mutations were detected: p.Ile144Thr and p.Thr287Ala in Iraqi and mixed ethnicity Balkan-North African participants, respectively. These missense mutations were evolutionarily conserved, possibly pathogenic, based on some prediction algorithms, and were not detected in any of healthy Iraqi (n = 60) and mixed ethnicity (n = 140), cancer free controls, respectively. Germline mutations in RAD51C contribute marginally to breast and ovarian cancer susceptibility in ethnically diverse, Jewish high risk families. The p.Thr287Ala missense mutation may be a recurring, pathogenic RAD51C mutation in ethnically diverse populations.

Keywords

Germline mutations RAD51C Breast cancer risk Jewish population 

Notes

Acknowledgments

We thank all individuals who participated to this study. This study was partially funded by the Israel Cancer Association. This work was done in partial fulfillment of the requirements for a Masters degree for Anya Kushnir at the Department of Human Genetics and Molecular Biology at the Tel-Aviv University, Tel-Aviv, Israel.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Anya Kushnir
    • 1
  • Yael Laitman
    • 1
  • Shani Paluch Shimon
    • 2
  • Raanan Berger
    • 2
    • 3
  • Eitan Friedman
    • 1
    • 3
    Email author
  1. 1.The Susanne Levy Gertner Oncogenetics UnitDanek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Tel-Aviv UniversityTel-Hashomer, Tel-AvivIsrael
  2. 2.The Oncology Institute, Chaim Sheba Medical Center, Tel-Aviv UniversityTel-AvivIsrael
  3. 3.The Sackler School of MedicineTel-Aviv UniversityTel-Hashomer, Tel-AvivIsrael

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