Abstract 1866: Polymorphisms in DNA double-strand break repair genes and end-joining capacity from sisters discordant for breast cancer from the New York site of the BCFR

Abstract

Abstract Dysfunction in DNA double strand break (DSB) repair increases breast cancer risk. Genetic variation could be an important factor in determining DSB capacity. However, data on the association of single nucleotide polymorphisms (SNPs) of DSB repair genes with phenotype and with breast cancer risk are limited. We determined genotypes for 25 DSB repair SNPs in a total of 298 families with discordant sisters for breast cancer, including 85 families with end-joining (EJ) capacity data available from the New York site of the Breast Cancer Family Registry (BCFR). We observed that XRCC4 variant (rs1056503) was associated with increased breast cancer risk with age-adjusted odds ratios (OR) of 1.67 (95% confidence interval (CI)=1.02-2.74) and a significant inverse effect of an XRCC5 variant (rs1051677) with an age-adjusted OR of 0.07 (95% CI=0.009-0.58). EJ capacities differed by different genotypes of BRCA1 among controls, and different genotypes of XRCC5 among cases and controls. However, in a final multivariable conditional logistic model, including RAD52 (rs11226), XRCC4 (rs1056503) and XRCC5 (rs3834), we did not observed any statistically significant genetic effect of DSB repair genes on breast cancer risk. Although these findings suggest that selected polymorphisms of DSB pathway genes were associated with EJ capacity, there were no main associations with breast cancer suggesting that DSB phenotype rather than genotype may be more important in predicting breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1866.