Rad51 Paralogs and the Risk of Unselected Breast Cancer: A Case-Control Study

A case-control study was conducted in which we evaluated the association between genetic variability of DNA repair proteins belonging to the Rad51 family and breast cancer (BrC) risk. In the study, 132 female BrC cases and 189 healthy control females were genotyped for a total of 14 common single nucleotide polymorphisms (SNPs) within Rad51 and Xrcc3. Moreover, our previously reported Rad51C genetic data were involved to explore the nonlinear interactions among SNPs within the three genes and effect of such interactions on BrC risk. The rare rs5030789 genotype (-4601AA) in Rad51 was found to significantly decrease the BrC risk (OR = 0.5, 95% CI: 0.3-1.0, p<0.05). An interaction between this SNP, rs2619679 and rs2928140 (both in Rad51), was found to result in a two three-locus genotypes -4719AA/-4601AA/2972CG and -4719AT/-4601GA/2972CC, both of which were found to increase the risk of BrC (OR = 8.4, 95% CI: 1.8-38.6, p<0.0001), instead. Furthermore, rare Rad51 rs1801320 (135CC) and heterozygous Xrcc3 rs3212057 (10343GA) genotypes were found to respectively increase (OR = 10.6, 95% CI: 1.9-198, p<0.02) and decrease (OR = 0.0, 95% CI: 0.0-NA, p<0.05) the risk of BrC. Associations between these SNPs and BrC risk were further supported by outcomes of employed machine learning analyses. In Xrcc3, the 4541A/9685A haplotype was found to be significantly associated with reduced BrC risk (OR = 0.5; 95% CI: 0.3-0.9; p<0.05). Concluding, our study indicates a complex role of SNPs within Rad51 (especially rs5030789) and Xrcc3 in BrC, although their significance with respect to the disease needs to be further clarified.