Source Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Department of Molecular Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Department of Molecular Genetics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences.

Background and Aim: Chronic hepatitis C virus (HCV) infection is well known risk factor for hepatocellular carcinoma (HCC). The aim of this study is to elucidate the genetic risk of development and recurrence of HCC in patients with HCV.

Methods: A total of 468 patients with HCV, including 265 with HCC were enrolled. We genotyped 89 SNPs in 81 genes expected to influence hepatocarcinogenesis using the iPLEX assay. Risk of HCC was clarified by stratifying patients into risk groups based on the multiplied Odds Ratio (MOR) for SNPs associated with HCC, and the cumulative effects on the development and reccurence of HCC were analyzed.

Results: Six SNPs associated with risk of HCC were identified (OR range: 0.29∼1.76). These included novel SNPs for hepatocarcinogenesis with HCV CCND2 rs1049606, RAD23B rs1805329, CEP164 rs573455, and GRP78rs430397 in addition to the known SNPs MDM2 rs2279744 and ALDH2 rs671. MOR analysis revealed that the highest risk group exerted about a 19 fold higher relative OR compared to the lowest risk group (p = 1.08 x 10 -5). Predicted 10 year HCC risk ranged from 1.7% to 96% depending on the risk group and the extent of fibrosis. Recurrence-free survival of RFA-treated HCC in the high risk group (n = 53) was lower than that of low risk group (n = 58, p = 0.038).

Conclusion: SNPs of CCND2, RAD23B, GRP78, CEP164, MDM2, and ALDH2 genes were significantly associated with development and recurrence of HCC in Japanese patients with HCV.