Polymorphisms of DNA repair genes in Korean hepatocellular carcinoma patients with chronic hepatitis B: Possible implications on survival

Abstract

Background & Aims: We aimed at determining whether single nucleotide polymorphisms (SNPs) of DNA repair genes influence the development and clinical outcomes of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Methods: We evaluated 14 SNPs of eight DNA repair genes in 708 patients with HCC and 388 HBsAg positive controls without HCC. The Kaplan-Meier methods with log-rank test and Cox regression models were used to compare survival of HCC patients according to the genotype. Results: The SNP of XRCC4 rs1805377 was significantly associated with decreased risk of HCC development (OR, 0.592; p = 0.028) and improved overall survival of patients with HCC (median survival time (MST) of 48, 72, and 89 months for the AA, AG, and GG genotypes, respectively; p = 0.044). In addition, SNP of OGG1 rs1053133 was significantly associated with postoperative recurrence (OR, 0.604; p = 0.049), tumor differentiation (OR, 0.571; p = 0.041), and improved survival of resected HCC (MST of 55 and 108 months for the GG and GC/CC genotypes, p = 0.001). The multivariate analysis showed that OGG1 rs1052133, XRCC1 rs25487, ERCC5 rs2018836, ERCC5 rs3818356, and XRCC4 rs1805377 had a significant effect on survival. Moreover, a strong dose-dependent association was observed between the number of putative high-risk genotypes of OGG1, XRCC1, ERCC5, and XRCC4 with the overall survival. The MST of HCC with ≤2 putative high-risk genotypes was significantly prolonged compared to those with ≥3 high-risk genotypes (76 vs. 46 months, respectively, p = 0.002). Conclusions: Polymorphisms of DNA repair genes play a potential role in the development, progression, and survival of Korean HCC patients with chronic HBV infection. © 2012 European Association for the Study of the Liver.