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, Pcombined = 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.
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Acknowledgements
The authors thank the subjects who agreed to participate in this study. We also thank the team members at Toranomon Hospital, Sapporo Kosei General Hospital, Hiroshima University Hospital and Hiroshima Liver Study Group for clinical sample collection. We thank T. Yokogi, Y. Hayashida and K. Izumoto for technical assistance, J. Sakamiya for clerical assistance and other members of the RIKEN Center for Genomic Medicine and Hiroshima University for assistance with various aspects of this study.
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K.C. conceived the study. D.M., H.O. and K.C. designed the study. D.M. and H.O. performed genotyping. D.M., H.O., C.N.H. and K.C. wrote the manuscript. T.M., T.T., M.K. and N.K. performed data analysis at the genome-wide phase. H. Abe and T.Y. performed functional analyses. H. Aikata, K.I., H.K., J.T. and K.C. managed DNA samples. D.M., H.O. and K.C. summarized the whole results. Y.N., N.K. and K.C. obtained funding for the study.
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Miki, D., Ochi, H., Hayes, C. et al. Variation in the DEPDC5 locus is associated with progression to hepatocellular carcinoma in chronic hepatitis C virus carriers. Nat Genet 43, 797–800 (2011). https://doi.org/10.1038/ng.876
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DOI: https://doi.org/10.1038/ng.876
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