Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers.

Miki D, Ochi H, Hayes CN, Abe H, Yoshima T, Aikata H, Ikeda K, Kumada H, Toyota J, Morizono T, Tsunoda T, Kubo M, Nakamura Y, Kamatani N, Chayama K.

Source

1] Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan. [2] Department of Medicine and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. [3].

Abstract

Chronic viral hepatitis is the most important risk factor for progression to hepatocellular carcinoma (HCC). To identify genetic risk factors for progression to HCC in individuals with chronic hepatitis C virus (HCV), we analyzed 467,538 SNPs in 212 Japanese individuals with chronic HCV with HCC and 765 individuals with chronic HCV without HCC. We identified one intronic SNP in the DEPDC5 locus on chromosome 22 associated with HCC risk and confirmed the association using an independent case-control population (710 cases and 1,625 controls). The association was highly significant when we analyzed the stages separately as well as together (rs1012068, P(combined) = 1.27 × 10(-13), odds ratio = 1.75). The significance level of the association further increased after adjustment for gender, age and platelet count (P = 1.35 × 10(-14), odds ratio = 1.96). Our findings suggest that common variants within the DEPDC5 locus affect susceptibility to HCC in Japanese individuals with chronic HCV infection.