Evaluation of RAD51C as cancer susceptibility gene in a large breast-ovarian cancer patient population referred for genetic testing

Breast Cancer Res Treat. 2012 May;133(1):393-8. doi: 10.1007/s10549-012-1998-4. Epub 2012 Feb 28.


Despite extensive analysis of the BRCA1 and BRCA2 genes, germline mutations are detected in <20% of families with a presumed genetic predisposition for breast and ovarian cancer. Recent literature reported RAD51C as a new breast cancer susceptibility gene. In this study, we report the analysis of 410 patients from 351 unrelated pedigrees. All were referred for genetic testing and we selected families with at least one reported case of ovarian cancer in which BRCA1&2 mutations were previously ruled out. We analyzed the coding exons, intron-exons boundaries, and UTRs of RAD51C. Our mutation analysis did not reveal any unequivocal deleterious mutation. In total 12 unique sequence variations were identified of which two were novel. Our study and others suggest a low prevalence of RAD51C mutations with an exception for some founder populations. This observation is in favor of the rare allele hypothesis in the debate over the nature of the genetic contribution to individual susceptibility to breast and ovarian cancer and further genome-wide studies in high risk families are warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics*
  • Humans
  • Male
  • Mutation, Missense
  • Pedigree
  • Polymorphism, Single Nucleotide


  • DNA-Binding Proteins
  • RAD51C protein, human