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J Hepatol. 2012 Mar;56(3):729-30. doi: 10.1016/j.jhep.2011.08.015. Epub 2011 Sep 29.

Genomic risk of hepatitis C-related hepatocellular carcinoma.

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Cancer Program, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.


To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P <1 10(⁻5)) in the genome-wide association study were further genotyped in 673 cases and 2596 controls. We found a previously unidentified locus in the 50 flanking region of MICA on 6p21.33 (rs2596542, P(combined) = 4.21 10(⁻13), odds ratio = 1.39) to be strongly associated with HCV induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 10(⁻8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 10(⁻13)).

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