Polymorphism of DNA repair gene XRCC1 and hepatitis-related hepatocellular carcinoma risk in Indian population.

Background: Hepatocellular carcinoma (HCC) is one of the life-threatening malignancies worldwide with hepatitis B and C virus infection as the major risk factor. The risk of HCC might also increase because of the hereditary genetic defects in DNA repair genes. In this regard, X-ray cross-complementing group 1 gene (XRCC1) is a major DNA repair gene involved in base excision repair (BER).

Aim: The present study was designed with an aim to find out any possible association between XRCC1 (codons 194, 280, and 399) polymorphisms and the risk of developing hepatitis virus-related HCC in Indian population.

Methods: A total of 407 subjects comprising (170 controls, 174 chronic viral hepatitis, and 63 HCC subjects) were included in the study. PCR-RFLP was used for the genotyping of the three codons of XRCC1.

Results: The study revealed that two genotypes Arg194Trp and Arg280His increased the risk of HCC by 2.27- (95% CI = 1.01-5.08; P < 0.001) and 4.95-folds (95% CI = 2.48-9.89; P < 0.001), respectively. Interestingly, the risk for HCC was further enhanced by 35.96 (95% CI = 11.64-110.91; P < 0.001) and 5.28 times (95% CI = 2.81-9.09; P < 0.001) when the genotype Arg280His was found in association with Arg194Trp and Arg399Gln, respectively.

Conclusion: These preliminary results suggest a positive association of XRCC1 genotypes and risk of hepatitis virus-related HCC in India.