Breast Cancer Susceptibility Gene in Base Excision Repair Pathway in a Southern Indian Population

Introduction: Breast cancer, the most complex multifactorial disease, one of the most common malignancies seen in females over the world. Single-Nucleotide Polymorphisms (SNPs) that occur in DNA repair genes are the contributors to cancer development as they lead to alteration in protein function, impair DNA damage responses, and result in loss of efficiency of DNA repair pathways. Aim: To determine the association of the two polymorphisms (rs25487 and rs1799782) of the gene XRCC1 involved in the Base Excision Repair (BER) pathway with breast cancer risk. Materials and Methods: In the present study, 200 breast cancer cases and 200 healthy age-matched controls were analysed with regard to the genotype distribution of XRCC1rs1799782 and rs25487 polymorphism using Taqman allelic discrimination assay by Real time PCR. Chi-square test was the statistical method used, and compliance of the genotype frequencies with Hardy-Weinberg equilibrium was verified. The relative risk was assessed by determining the Odds Ratios (OR) and 95% Confidence Intervals (CI). Insilico studies were carried out for identifying the possible functional and deleterious nsSNPs in XRCC1 gene. Results: With regard to SNPs involved in the genes that play a role in the BER pathway, a significant association was found for the G/A heterozygous genotype of the XRCC1 (rs25487) (OR; 1.79; 95% CI, 1.17-2.73; p-value: 0.006) with the risk of breast carcinoma. Also, an association was observed between the A/A homozygous genotype of the XRCC1 (rs25487) (OR; 2.08; 95% CI. 1.08-4; p-value 0.02) and breast carcinoma risk. There was a lack of association of the CT/TT genotype of the XRCC1 (rs1799782) (OR, 1.12; 95% CI, 0.69-1.80; P 0.63) with breast carcinoma risk. The insilco studies revealed structural variation in XRCC1 gene with respect to rs25487. Conclusion: The variant rs25487 of XRCC1 gene was associated with the risk of breast carcinoma, but no association was found with regard to frequency of the rs1799782 variant in the XRCC1 gene. The stability prediction and pathogenicity analysis with computational tools revealed the nsSNPrs25487 interfering with function and structure of the XRCC1 protein. The data suggest that the variant of XRCC1 (rs25487) may contribute to breast cancer susceptibility, extensive study linking DNA repair, environmental factors and ethnicity are needed.