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

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

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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 5-2 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).

Original languageEnglish
Pages (from-to)455-458
Number of pages4
JournalNature Genetics
Volume43
Issue number5
DOIs
Publication statusPublished - 01-01-2011

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Genome-Wide Association Study
Hepacivirus
Hepatocellular Carcinoma
Chronic Hepatitis C
Single Nucleotide Polymorphism
5' Flanking Region
Genetic Predisposition to Disease
Alleles
Odds Ratio
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Kumar, V., Kato, N., Urabe, Y., Takahashi, A., Muroyama, R., Hosono, N., ... Matsuda, K. (2011). Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. Nature Genetics, 43(5), 455-458. https://doi.org/10.1038/ng.809
Kumar, Vinod ; Kato, Naoya ; Urabe, Yuji ; Takahashi, Atsushi ; Muroyama, Ryosuke ; Hosono, Naoya ; Otsuka, Motoyuki ; Tateishi, Ryosuke ; Omata, Masao ; Nakagawa, Hidewaki ; Koike, Kazuhiko ; Kamatani, Naoyuki ; Kubo, Michiaki ; Nakamura, Yusuke ; Matsuda, Koichi. / Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. In: Nature Genetics. 2011 ; Vol. 43, No. 5. pp. 455-458.
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Kumar, V, Kato, N, Urabe, Y, Takahashi, A, Muroyama, R, Hosono, N, Otsuka, M, Tateishi, R, Omata, M, Nakagawa, H, Koike, K, Kamatani, N, Kubo, M, Nakamura, Y & Matsuda, K 2011, 'Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma', Nature Genetics, vol. 43, no. 5, pp. 455-458. https://doi.org/10.1038/ng.809

Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma. / Kumar, Vinod; Kato, Naoya; Urabe, Yuji; Takahashi, Atsushi; Muroyama, Ryosuke; Hosono, Naoya; Otsuka, Motoyuki; Tateishi, Ryosuke; Omata, Masao; Nakagawa, Hidewaki; Koike, Kazuhiko; Kamatani, Naoyuki; Kubo, Michiaki; Nakamura, Yusuke; Matsuda, Koichi.

In: Nature Genetics, Vol. 43, No. 5, 01.01.2011, p. 455-458.

Research output: Contribution to journalArticle

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AU - Kato, Naoya

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AU - Hosono, Naoya

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AU - Tateishi, Ryosuke

AU - Omata, Masao

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AU - Koike, Kazuhiko

AU - Kamatani, Naoyuki

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AU - Nakamura, Yusuke

AU - Matsuda, Koichi

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N2 - 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 5-2 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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