Correlation between Selected XRCC2, XRCC3 and RAD51 Gene Polymorphisms and Primary Breast Cancer in Women in Pakistan


Genetic polymorphisms in homologous recombination repair genes cause an abnormal development ofcancerous cells. In the present study we evaluated the possibility of breast cancer association with single nucleotidepolymorphisms of RAD51, XRCC2 and XRCC3 genes. Polymorphisms selected in this study were RAD51 135G/C,XRCC2 Arg188His; and XRCC3 Thr241Met. Each polymorphism was genotyped using Polymerase chainreaction-restriction fragment length polymorphism in study cohort of 306 females (156 breast cancer patientsand 150 controls). We observed that heterozygous variant genotype (GC) of RAD51 135 G/C polymorphism wasassociated with a significantly (OR=2.70; 95%CI (0.63-1.79); p<0.03) increased risk of breast cancer. In caseof the XRCC3 gene we observed that frequency of heterozygous (OR=2.88; 95%CI (1.02-8.14); p<0.02) andhomozygous (OR=1.46; 95%CI (0.89-2.40); p<0.04) genotype of Thr241Met polymorphism were significantlyhigher in breast cancer patients. For the Arg188His polymorphism of XRCC2, ~2fold increase in breast cancerrisk (OR=1.6, 95%CI = 0.73-3.50) was associated with GA genotype with a p value for trend of 0.03. Our resultssuggest that the 135G/C polymorphism of the RAD51, Thr241Met polymorphism of XRCC3 and Arg188Hispolymorphism of XRCC2 can be independent markers of breast cancer risk in Pakistan.