Association of RAD51, XRCC1, XRCC2, and XRCC3 Polymorphisms with Risk of Breast Cancer.

Abstract

Background: DNA repair genes are among the low-penetrance genes implicated in breast cancer. However variants of DNA repair genes may alter their protein function thus leading to carcinogenesis. Breast cancer is the most common cancer among women in India. The aim of the present study was to identify association, if any, of single nucleotide polymorphisms (SNP's) in four genes involved in DNA repair pathways including, RAD51 rs1801320, XRCC1 rs25487, XRCC2 rs3218536, and XRCC3 rs861539 with the risk of breast cancer. Materials and Methods: In this case-control study 611 female subjects (311 breast cancer patients and 300 healthy controls) were screened for four SNPs using polymerase chain reaction-restriction fragment length polymorphism analyses. Multifactor dimensionality reduction (MDR) analysis was performed to estimate the gene-gene interaction. Protein-protein interaction network analysis were studied using the STRING database. Results: The GC genotype (p = 0.018) and the combined GC+CC (p = 0.03) genotypes of RAD51 rs1801320 were significantly associated with reduced risk of breast cancer. The CT genotype (p = 0.0001), the combined CT+TT genotypes (p = 0.0002), and the T allele (p = 0.0019) of XRCC3 rs861539 polymorphism were associated with reduced risk of the breast cancer. No association of XRCC1 rs25487 and XRCC2 rs3218536 polymorphisms with breast cancer was observed. MDR analysis indicated a positive interaction between XRCC3 and XRCC2. String network analysis showed that the RAD51, XRCC1, XRCC2, and XRCC3 proteins are in strong interaction with each other and other breast cancer-related proteins such as BRCA2. Conclusion: RAD51 rs1801320 and XRCC3 rs861539 polymorphisms were associated with reduced risk of breast cancer. There is evidence of positive interactions among XRCC1, XRCC2, XRCC3, and RAD51.