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Analyses of the individual risk for hepatocellular carcinoma by large scale search of single nucleotide polymorphisms of cytokine genes

Research Project

Project/Area Number 16590578
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionThe University of Tokyo Hospital

Principal Investigator

KATO Naoya  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (90313220)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Haruhiko  The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (60240305)
TATEISHI Keisuke  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20396948)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsHepatitis C / SNP / Hepatocellular carcinoma / UGT1A7 / Cytokine / MDM2 / SCYB14 / CRHR2 / GFRA1 / 肝細胞癌
Research Abstract

Genetic polymorphisms of UGT1A7, which detoxifies endogenous and environmental carcinogens, have been reported to be associated with HCC in German populations. In this study, we evaluated the association of this gene with the risk of HCC in Japanese HCV-infected patients. Genetic polymorphisms of UGT1A7 were investigated in 280 Japanese patients (122 with HCC) with chronic HCV infections. We designated the UGT1A7^*1 allele (a haplotype confering higher activity) as H and the ^*2, ^*3, and ^*4 alleles (haplotypes confering lower activity) as L. The proportions of UGT1A7 L/L and H/L alleles in patients with HCC (25% and 45%, respectively) were higher than those in patients without HCC (15% and 39%, respectively) with an odds ratio of 2.73 (95% CI:1.40-5.35) and 1.80 (95% CI:1.05-3.09), respectively, compared with the UGT1A7 H/H alleles. The UGT1A7 polymorphisms were associated with the presence of HCC in Japanese HCV-infected patients.
To search for SNPs in HCC susceptibility genes, 393 S … More NPs in 171 candidate genes were examined in 188 Japanese patients with chronic HCV infection, including 77 patients with HCC. HCC-related SNPs were then examined in another 188 patients (93 with HCC) with chronic HCV infection. Of the 393 SNPs, 31 SNPs in 29 genes were significantly associated with HCC based on an initial screening (P < 0.05). Of these 31 SNPs, three SNPs of three genes (SCYB14, GFRA1, and CRHR2) were significantly associated with HCC in a secondary screening. In conclusion, These SNPs located in the SCBY14, CRHR2, and GFRA1 genes will be used as markers to identify a subgroup of Japanese patients with chronic HCV infection who are at high risk of developing HCC.
A single nucleotide polymorphisms in the promoter region of MDM2 gene, SNP309, has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. However, the association of SNP309 with HCC is unknown. We evaluated the association of SNP309 with the risk of HCC development among Japanese patients with chronic HCV infection. We genotyped the SNP309 at the MDM2 promoter in 435 Japanese patients with chronic HCV infection including 187 patients with HCC, as well as 48 healthy subjects, using a fluorogenic polymerase chain reaction. Presence of SNP was also confirmed by direct sequencing of the MDM2 promoter region. The proportion of G/G genotype of the SNP309 in patients with HCC (33%) was significantly higher than that in patients without HCC (23%), with an odds ratio of 2.28 (95% confidence interval, 1.30-3.98). The MDM2 promoter SNP309 is associated with the presence of HCC in Japanese patients with chronic hepatitis C. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (22 results)

All 2006 2005 2004

All Journal Article (20 results) Book (2 results)

  • [Journal Article] Hepatitis C virus core protein is a potent inhibitor of RNA silencing-based antiviral response.2006

    • Author(s)
      Wang Y et al.
    • Journal Title

      Gastroenterology 130

      Pages: 883-892

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Hepatitis C virus core protein is a potent inhibitor of RNA silencing-based antiviral response.2006

    • Author(s)
      Wang Y, Kato N, Amarsanaa J, Dharel N, Otsuka M, Taniguchi H, Kawabe T, Omata M.
    • Journal Title

      Gastroenterology 130

      Pages: 883-892

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Gene expressions associated with chemosensitivity in human hepatoma cells.2006

    • Author(s)
      Hoshida Y et al.
    • Journal Title

      Hepatogastroenterol (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Acyclic retinoid inhibits human hepatoma cell growth by suppressing FGF-mediated signaling pathways.2005

    • Author(s)
      Shao R-X et al.
    • Journal Title

      Gastroenterology 128

      Pages: 86-95

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Large-scale search of single nucleotide polymorphisms for hepatocellular carcinoma susceptibility genes in patients with hepatitis C.2005

    • Author(s)
      Kato N et al.
    • Journal Title

      Hepatology 42

      Pages: 846-853

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Hepatitis C virus core protein and hepatitis activity are associated through transactivation of interleukin-8.2005

    • Author(s)
      Hoshida Y et al.
    • Journal Title

      J Infect Dis 192

      Pages: 266-275

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Acyclic retinoid inhibits human hepatoma cell growth by suppressing fibroblast growth factor-mediated signaling pathways.2005

    • Author(s)
      Shao R-X, Otsuka M, Kato N, Taniguchi H, Hoshida Y, Moriyama M, Kawabe T, Omata M.
    • Journal Title

      Gastroenterology 128

      Pages: 86-95

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Large-scale search of single nucleotide polymorphisms for hepatocellular carcinoma susceptibility genes in patients with hepatitis C.2005

    • Author(s)
      Kato N, Ji G, Wang Y, Baba M, Hoshida Y, Otsuka M, Taniguchi H, Moriyama M, Dharel N, Goto T, Shao R-X, Matsuura T, Ishii K, Shiina S, Kawabe T, Muramatsu M, Omata M.
    • Journal Title

      Hepatology 42

      Pages: 846-853

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatitis C virus core protein and hepatitis activity are associated through transactivation of interleukin-8.2005

    • Author(s)
      Hoshida Y, Kato N, Yoshida H, Wang Y, Tanaka M, Goto T, Otsuka M, Taniguchi H, Moriyama M, Imazeki F, Yokosuka O, Kawabe T, Shiratori Y, Omata M.
    • Journal Title

      J Infect Dis 192

      Pages: 266-275

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatic gene expression profiles associated with fibrosis progression and hepatocarcinogenesis in hepatitis C patients.2005

    • Author(s)
      Shao R-X et al.
    • Journal Title

      World J Gastroenterol 11

      Pages: 1995-1999

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses.2005

    • Author(s)
      Otsuka M et al.
    • Journal Title

      Hepatology 41

      Pages: 1004-1012

    • Related Report
      2005 Annual Research Report
  • [Journal Article] UGT1A7 genetic polymorphisms are associated with HCC in Japanese patients with hepatitis C virus infection.2004

    • Author(s)
      Wang Y et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 2441-2446

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatitis C virus core protein upregulates transforming growth factor-betal transcription.2004

    • Author(s)
      Taniguchi H et al.
    • Journal Title

      J Med Virol 72

      Pages: 52-59

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma in Japanese patients with hepatitis C virus infection.2004

    • Author(s)
      Wang Y, Kato N, Hoshida Y, Otsuka M, Taniguchi H, Moriyama M, Shiina S, Kawabe T, Ito YM, Omata M.
    • Journal Title

      Clin Cancer Res 10

      Pages: 2441-2446

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Hepatitis C virus core protein upregulates transforming growth factor-β1 transcription.2004

    • Author(s)
      Taniguchi H, Kato N, Otsuka M, Goto T, Yoshida H, Shiratori Y, Omata M.
    • Journal Title

      J Med Virol 72

      Pages: 52-59

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] UGT1A7 genetic polymorphisms are associated with HCC in Japanese patients with hepatitis C virus infection2004

    • Author(s)
      Wang Y, et al.
    • Journal Title

      Clin Cancer Res 10

      Pages: 2441-2446

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hepatitis C virus core protein upregulates transforming growth factor-beta1 transcription2004

    • Author(s)
      Taniguchi H et al.
    • Journal Title

      J Med Virol 72

      Pages: 52-59

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Vitamin K2 inhibits the growth and invasiveness of HCC cells via protein kinase A activation2004

    • Author(s)
      Otsuka M et al.
    • Journal Title

      Hepatology 40

      Pages: 243-251

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Genes associated with human HCC cell chemosensitivity to 5-FU plus IFN-alpha combination chemotherapy2004

    • Author(s)
      Moriyama M et al.
    • Journal Title

      Int J Oncol 25

      Pages: 1279-1287

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A simple combination of serum type IV collagen and PT to diagnose cirrhosis in patients with chronic active hepatitis C2004

    • Author(s)
      Qiu Y et al.
    • Journal Title

      Hepatol Res 30

      Pages: 214-220

    • Related Report
      2004 Annual Research Report
  • [Book] Therapy for Viral Hepatitis and Prevention of Hepatocellular Carcinoma2004

    • Author(s)
      Kato N et al.
    • Publisher
      Springer-Verlag Tokyo
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Book] New antivirals against wild-type and lamivudine-resistant hepatitis B virus. In : Therapy for Viral Hepatitis and Prevention of Hepatocellular Carcinoma. (Omata M, Okita K eds.)2004

    • Author(s)
      Kato N, Ono-Nita SK, Omata M.
    • Publisher
      Springer-Verlag Tokyo.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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