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

doi:10.1038/ng.809

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

Research output: Contribution to journal › Article › peer-review

343 Citations (Scopus)

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 language	English
Pages (from-to)	455-458
Number of pages	4
Journal	Nature Genetics
Volume	43
Issue number	5
DOIs	https://doi.org/10.1038/ng.809
Publication status	Published - 05-2011
Externally published	Yes

All Science Journal Classification (ASJC) codes

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ng.809

Cite this

@article{7d29b90518d14228bc7d3ac255383587,

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 5-2 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).",

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

note = "Funding Information: We would like to thank all the subjects and the members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan who donated their DNA for this work. We also thank the technical staff of the Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, and the Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo. This work was conducted as a part of the BioBank Japan Project that was supported by the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government.",

year = "2011",

month = may,

doi = "10.1038/ng.809",

language = "English",

volume = "43",

pages = "455--458",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

}

TY - JOUR

T1 - Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma

AU - Kumar, Vinod

AU - Kato, Naoya

AU - Urabe, Yuji

AU - Takahashi, Atsushi

AU - Muroyama, Ryosuke

AU - Hosono, Naoya

AU - Otsuka, Motoyuki

AU - Tateishi, Ryosuke

AU - Omata, Masao

AU - Nakagawa, Hidewaki

AU - Koike, Kazuhiko

AU - Kamatani, Naoyuki

AU - Kubo, Michiaki

AU - Nakamura, Yusuke

AU - Matsuda, Koichi

N1 - Funding Information: We would like to thank all the subjects and the members of the Rotary Club of Osaka-Midosuji District 2660 Rotary International in Japan who donated their DNA for this work. We also thank the technical staff of the Laboratory for Genotyping Development, Center for Genomic Medicine, RIKEN, and the Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, the University of Tokyo. This work was conducted as a part of the BioBank Japan Project that was supported by the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government.

PY - 2011/5

Y1 - 2011/5

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).

AB - 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).

UR - https://www.scopus.com/pages/publications/85027954267

UR - https://www.scopus.com/pages/publications/85027954267#tab=citedBy

U2 - 10.1038/ng.809

DO - 10.1038/ng.809

M3 - Article

AN - SCOPUS:85027954267

SN - 1061-4036

VL - 43

SP - 455

EP - 458

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this