RT Journal Article SR Electronic T1 A role for XRCC2 gene polymorphisms in breast cancer risk and survival JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 477 OP 484 DO 10.1136/jmedgenet-2011-100018 VO 48 IS 7 A1 Wei-Yu Lin A1 Nicola J Camp A1 Lisa A Cannon-Albright A1 Kristina Allen-Brady A1 Sabapathy Balasubramanian A1 Malcolm W R Reed A1 John L Hopper A1 Carmel Apicella A1 Graham G Giles A1 Melissa C Southey A1 Roger L Milne A1 Jose I Arias-Pérez A1 Primitiva Menéndez-Rodríguez A1 Javier Benítez A1 Magdalena Grundmann A1 Natalia Dubrowinskaja A1 Tjoung-Won Park-Simon A1 Thilo Dörk A1 Montserrat Garcia-Closas A1 Jonine Figueroa A1 Mark Sherman A1 Jolanta Lissowska A1 Douglas F Easton A1 Alison M Dunning A1 Preetha Rajaraman A1 Alice J Sigurdson A1 Michele M Doody A1 Martha S Linet A1 Paul D Pharoah A1 Marjanka K Schmidt A1 Angela Cox YR 2011 UL http://jmg.bmj.com/content/48/7/477.abstract AB Background The XRCC2 gene is a key mediator in the homologous recombination repair of DNA double strand breaks. It is hypothesised that inherited variants in the XRCC2 gene might also affect susceptibility to, and survival from, breast cancer.Methods The study genotyped 12 XRCC2 tagging single nucleotide polymorphisms (SNPs) in 1131 breast cancer cases and 1148 controls from the Sheffield Breast Cancer Study (SBCS), and examined their associations with breast cancer risk and survival by estimating ORs and HRs, and their corresponding 95% CIs. Positive findings were further investigated in 860 cases and 869 controls from the Utah Breast Cancer Study (UBCS) and jointly analysed together with available published data for breast cancer risk. The survival findings were further confirmed in studies (8074 cases) from the Breast Cancer Association Consortium (BCAC).Results The most significant association with breast cancer risk in the SBCS dataset was the XRCC2 rs3218408 SNP (recessive model p=2.3×10−4, minor allele frequency (MAF)=0.23). This SNP yielded an ORrec of 1.64 (95% CI 1.25 to 2.16) in a two-site analysis of SBCS and UBCS, and a meta-ORrec of 1.33 (95% CI 1.12 to 1.57) when all published data were included. This SNP may mark a rare risk haplotype carried by two in 1000 of the control population. Furthermore, the XRCC2 coding R188H SNP (rs3218536, MAF=0.08) was significantly associated with poor survival, with an increased per-allele HR of 1.58 (95% CI 1.01 to 2.49) in a multivariate analysis. This effect was still evident in a pooled meta-analysis of 8781 breast cancer patients from the BCAC (HR 1.19, 95% CI 1.05 to 1.36; p=0.01).Conclusions These findings suggest that XRCC2 SNPs may influence breast cancer risk and survival.