The variant E233G of the RAD51D gene could be a low-penetrance allele in high-risk breast cancer families without BRCA1/2 mutations

Int J Cancer. 2004 Jul 20;110(6):845-9. doi: 10.1002/ijc.20169.


Six SNPs have been detected in the DNA repair genes RAD51C and RAD51D, not previously characterized. The novel variant E233G in RAD51D is more highly represented in high-risk, site-specific, familial breast cancer cases that are not associated with the BRCA1/2 genes, with a frequency of 5.74% (n = 174) compared to a control population (n = 567) and another subset of breast cancer patients (n = 765) with a prevalence of around 2% only (comparison to controls, OR = 2.6, 95% CI 1.12-6.03; p < 0.021). We found that the immunohistochemical profile detected in available tumors from these patients differs slightly from those described in non-BRCA1/2 tumors. Finally, the structural prediction of the putative functional consequence of this change indicates that it can diminish protein stability and structure. This suggests a role for E233G as a low-penetrance susceptibility gene in the specific subgroup of high-risk familial breast cancer cases that are not related to BRCA1/2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Amino Acid Substitution
  • Breast Neoplasms / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Frequency
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Humans
  • Middle Aged
  • Mutation
  • Mutation, Missense
  • Ovarian Neoplasms / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Reference Values


  • DNA-Binding Proteins
  • RAD51D protein, human