Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women.

Abstract

BackgroundHomologous recombination repair (HRR) accurately repairs the DNA double-strand breaks (DSBs) and is crucial for genome stability. Genetic polymorphisms in crucial HRR pathway genes might affect genome stability and promote tumorigenesis. Up to our knowledge, the present study is the first to investigate the impact of HRR gene polymorphisms on BC development in South Indian women. The present population-based case-control study investigated the association of polymorphisms in three key HRR genes (XRCC2-Arg188His, XRCC3-Thr241Met and RAD51-G135C) with BC risk.Materials and methodsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping the HRR variants in 491 BC cases and 493 healthy women.ResultsWe observed that the XRCC3 Met allele was significantly associated with BC risk [OR:1.27 (95% CI: 1.02–1.60); p = 0.035]. In addition, the homozygous mutant (C/C) genotype of RAD51 G135C variant conferred 2.19 fold elevated risk of BC [OR: 2.19 (95% CI: 1.06–4.54); p = 0.034]. Stratified analysis of HRR variants and BC clinicopathological features revealed that the XRCC3-Thr241Met and RAD51-G135C variants are associated with BC progression. Combined SNP analysis revealed that the individuals with RAD51-C/C, XRCC2-Arg/Arg, and XRCC3-Thr/Thr genotype combination have three-fold increased BC risk.ConclusionThe present study imparts additional evidence that genetic variants in crucial HRR pathway genes might play a pivotal role in modulating BC risk in South Indian women.