Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma

Nature Genetics doi:10.1038/ng.809.

Vinod Kumar,Naoya Kato,Yuji Urabe,Atsushi Takahashi,Ryosuke Muroyama,Naoya Hosono,Motoyuki Otsuka,Ryosuke Tateishi,Masao Omata,Hidewaki Nakagawa,Kazuhiko Koike,Naoyuki Kamatani,Michiaki Kubo,Yusuke Nakamura & Koichi Matsuda

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan. Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan. Unit of Disease Control Genome Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan. Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

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 2,890 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 2,596 controls. We found a previously unidentified locus in the 5' 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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