Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma : Nature Genetics : Nature Publishing Group

Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma
Vinod Kumar,1, 2 Naoya Kato,3 Yuji Urabe,1 Atsushi Takahashi,2 Ryosuke Muroyama,3 Naoya Hosono,2 Motoyuki Otsuka,4 Ryosuke Tateishi,4 Masao Omata,4 Hidewaki Nakagawa,2 Kazuhiko Koike,4 Naoyuki Kamatani,2 Michiaki Kubo,2 Yusuke Nakamura1, 2 & Koichi Matsuda1

Affiliations
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Vinod Kumar,Yuji Urabe,Yusuke Nakamura &Koichi Matsuda
Center for Genomic Medicine, The Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Vinod Kumar,Atsushi Takahashi,Naoya Hosono,Hidewaki Nakagawa,Naoyuki Kamatani,Michiaki Kubo &Yusuke Nakamura
Unit of Disease Control Genome Medicine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Naoya Kato &Ryosuke Muroyama
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Motoyuki Otsuka,Ryosuke Tateishi,Masao Omata &Kazuhiko Koike

Contributions
K.M. and Y.N. conceived of the study; Y.N., V.K., M.K. and K.M. designed the study; V.K., Y.U., R.M. and N.H. performed genotyping; V.K., Y.N. and K.M. wrote the manuscript; A.T. and N. Kamatani performed quality control at the genome-wide phase; Y.N., K.M., H.N. and M.K. managed DNA and serum samples belonging to BioBank Japan; N. Kato, R.T., M. Otsuka, M. Omata and K.K. managed replication DNA and serum samples; V.K. analyzed the data, performed VNTR genotyping, ELISA and summarized the whole results; Y.N. obtained funding for the study.

Competing financial interests
The authors declare no competing financial interests.

Corresponding author
Correspondence to: Koichi Matsuda

Journal name: Nature Genetics
Year published: (2011)
DOI: doi:10.1038/ng.809
Received20 July 2010
Accepted23 March 2011
Published online17 April 2011


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, Pcombined = 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).


Figures at a glance
Figure 1: Regional association plot at rs2596542.
Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma : Nature Genetics : Nature Publishing Group



HEPATOLOGÍA
Nuevos datos sobre la relación genética entre el virus de la hepatitis C y el carcinoma hepatocelular
JANO.es y agencias · 18 Abril 2011 12:43

.Dos estudios publicados por investigadores japoneses han permitido identificar mutaciones específicas.

Virus de la hepatitis C.


Dos estudios publicados en la edición digital de Nature Genetics avanzan en el conocimiento de los vínculos genéticos que existen entre cáncer de hígado y la infección por el virus de la hepatitis C. Más de 170 millones de personas en todo el mundo están infectadas con el virus de la hepatitis C, principal factor de riesgo de la cirrosis hepática y el carcinoma hepatocelular.

Los científicos presentan el genoma de un carcinoma hepatocelular positivo para el virus de la hepatitis C (VHC), así como una localización de riesgo genético para el carcinoma hepatocelular (HCC) inducido por el VHC.

El equipo de Tatsuhiro Shibata, del Instituto de Investigación del Centro Nacional del Cáncer en Tokio, secuenció un tumor de carcinoma hepatocelular positivo para el virus de la hepatitis C y lo confrontó con células normales de un varón japonés. Los científicos identificaron miles de mutaciones específicas del tumor.

Por otro lado, investigadores de la Universidad de Tokio dirigidos por Koichi Matsuda, realizaron un análisis amplio de genoma de 1.394 individuos de ancestros japoneses con carcinoma hepatocelular inducido por el virus de la hepatitis C. Los autores identificaron una localización en el cromosoma 6p21 que está fuertemente asociada al carcinoma hepatocelular inducido por el VHC.



Nature Genetics 2011; doi:10.1038/ng.804
High-resolution characterization of a hepatocellular carcinoma genome : Nature Genetics : Nature Publishing Group

Nature Genetics 2011;doi:10.1038/ng.809
Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma : Nature Genetics : Nature Publishing Group

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