Clinicopathological Association of DNA Repair Gene Polymorphisms in Colorectal Cancer Patients

Abstract

Several polymorphisms in DNA repair genes, especially ERCC1 C118T, ERCC2 Lys751Gln and XRCC1 Arg399Gln have been found to affect treatment efficacy and prognosis in patients with colorectal cancer (CRC). However, scarce reports available on the association of these polymorphisms with clinicopathological parameters. As clinicopathological factors provide important information to determine prognosis in CRC, present study evaluated association of DNA repair gene polymorphisms with clinicopathological parameters. ERCC1 C118T, ERCC2 Lys751Gln and XRCC1 Arg399Gln polymorphisms were studied by PCRRFLP in 143 primary CRC patients. For ERCC1 C118T polymorphism, predominance of heterozygous C/T (56%) was noted compared to wild type C/C (29%) and variant T/T (15%) genotypes. ERCC2 Lys751Gln polymorphism showed 44% of wild type A/A, 40% of heterozygous A/C, and 16% of variant C/C genotypes. XRCC1 Arg399Gln polymorphism displayed wild type G/G (48%), heterozygous G/A (42%), and variant A/A (10%). In relation to clinicopathological parameters, ERCC1 C118T polymorphism was significantly associated with tumor site (P=0.021); tumor location (P=0.039); and tumor differentiation (P=0.041). Moreover, a significant correlation of ERCC2 Lys751Gln polymorphism was noted with lymphocytic stromal response (P=0.026) and necrosis (P=0.041). However, XRCC1 Arg399Gln polymorphism was not significantly associated with clinicopathological factors. Further, a significant positive correlation was observed between ERCC2 and XRCC1 polymorphism (P=0.002). To conclude, higher frequency of ERCC1 118 variant C/T and T/T genotypes was noted in patients with colon cancer and right side located tumors. Variant C allele of ERCC2 751 polymorphism was associated with less aggressive colorectal tumors. Moreover, significant association between ERCC2 and XRCC1 polymorphisms proposes interlink of genes of different DNA repair pathways in CRC.