title: Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma.
abstract: 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)).
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.forename: Naoya
authors.initials: N
authors.lastname: Kato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Urabe
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Muroyama
authors.forename: Naoya
authors.initials: N
authors.lastname: Hosono
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Tateishi
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
authors.forename: Hidewaki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Koike
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005805:Genes, MHC Class I; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007564:Japan; D008113:Liver Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012307:Risk Factors
chemical_list: D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A