A Single Nucleotide Polymorphism in the 5' Untranslated Region of RAD51 and Risk of Cancer Among BRCA1/2 Mutation Carriers

Cancer Epidemiol Biomarkers Prev. 2001 Sep;10(9):955-60.


RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 "c" allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Australia
  • BRCA1 Protein / genetics
  • BRCA2 Protein
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Israel
  • Jews / genetics
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / genetics*
  • Polymorphism, Genetic
  • Rad51 Recombinase
  • Transcription Factors / genetics
  • United States


  • BRCA1 Protein
  • BRCA2 Protein
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Transcription Factors
  • RAD51 protein, human
  • Rad51 Recombinase