Mismatch repair polymorphisms as markers of breast cancer prevalence in the breast cancer family registry

Background: Major breast cancer susceptibility genes involved in DNA repair, including BRCA1 and BRCA2, have been identified. However, mutations in these genes account for only 5-10% of identified breast cancer cases. Additional DNA repair pathway genes may also contribute to susceptibility. Materials and Methods: We investigated the association between 12 single nucleotide polymorphisms (SNPs) in mismatch repair (MMR) genes and breast cancer risk among 313 sister-sets enrolled in the New York site of the Breast Cancer Family Registry (BCFR) (n=744) using conditional logistic regression analysis. Results: An increase in breast cancer risk was observed for women with the MUTYH-rs3219489 variant allele (odds ratio (OR)=2.23, 95% confidence interval (CI)=1.10-4.52) and for women with the MSH2-rs2303428 variant allele (OR=1.73, 95% CI=1.00-2.99). Conclusion: Deficiencies in DNA repair pathways, such as MMR, have implications for the onset of familial breast cancer.