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Viral mutations and host diversities that contribute to hepatocarcinogenesis

Research Project

Project/Area Number 14570449
Research Category

Grant-in-Aid for Scientific Research (C)

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

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) KANAI Fumihiko  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (70334399)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsHepatitis C / SNP / Hepatocellular carcinoma / Hplotype / Hepatitis B virus X protein / Hepatitis C virus core protein / Interleukin-1β / UGT1A7 / c型肝炎ウイルスコア蛋白 / インターロイキン8 / B型肝炎ウィルス
Research Abstract

The natural history of hepatitis virus infection consists of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, the factors influencing disease progression to HCC have not been well elucidated. Here, we studied viral mutations and host diversities that contribute to hepatocarcinogenesis. 1) WBC DNAs were extracted from sera of 1.000 patients with hepatitis 13/C after obtaining written informed consent, and data base containing clinical data of these patients were constructed. Then, WBC DNA samples of 500 patients were anonymized by the method we established. 2) By analyzing hepatitis B virus (HBV) X gene nucleotide sequence in patients with/without HOC, it was revealed that amino acid substitution in codon 38 in HBx is significantly related with HOC. 3) Amino acid changes in C-terminal hydrophobic region of hepatitis C virus (HCV) core were observed more frequently in the interferon biological responders (BR) compared to interferon noivresponders (NR). Activatio … More n of Interleukin (IL)-8 promoter by core proteins significantly decreased after interferon therapy in the BR group compared to the NR group. Differences in amino acid sequence of HCV core possibly correlate with hepatitis activity by modulating IK-8 induction in HCV infected patients. 4) The effect of HCV core protein, HBx protein, and hepatitis delta virus large antigen on intracellular signaling pathway was determined. 5) Genetic polymorphsims of uidine 5'-diphosphate-glucuronosyltransferase 1A7 (UGT 1A7) and 1L-1β were investigated in 280 Japanese patients (122 with HCC) with chronic HCV infections. The proportions of UCT1A7 low activity allele (L)/L and high activity allel (H)/L in patients with HOC (25% and 45%, respectively) were higher than those in patients without HOC (15% and 39%, respectively) with an odds ratio of 2.7 and 1.8, respectively, comared with the UGT1A7 H/H. The IL-1β/-31 T/T genotype showed a significant association with the presence of HOC compared with the C/C genotype with an odds ratio of 2.9. 6) To search of single nucleotide polymorphisms(SNPs) for HOC susceptibility genes, 394 SNPs derived from 172 candidate genes were examined in 376 Japanese patients (including 170patients with HOC) with chronic HCV infection. Three SNPs derived from three genes were significantly associated with HOC. These SNPs and haplotypes will be used as markers to identify a subgroup at higher risk of HOC in Japanese patients with chronic HCV infection. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Wang Y, Kato N, et al.: "Interleukin-1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection."Hepatology. 37. 65-71 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Goto T, Kato N, et al.: "Hepatitis B virus HBx and the large hepatitis Delta antigen synergistically activate the SRE-dependent pathway."J Infect Dis. 187. 820-828 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hara K, Kato N, et al.: "Establishment of a method of anonymization of DNA samples in genetic research."J Hum Genet. 48. 327-330 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Taniguchi H, Kato N, et al.: "Hepatitis C virus core protein upregulates transforming growth factor-β1 transcription."J Med Virol. 72. 52-59 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang Y, Kato N, et al.: "UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma in Japanese patients with hepatitis C virus infection."Clin Cancer Res. 10(in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato N, et al.: "Induction of proliferation-related signals by hepatitis C virus.In : Growth, proliferation, and apoptosis in hepatocytes."Okita K ed., Springer-Verlag Tokyo. 81-98 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kato N, Yoshida H, Otsuka M, Shiratori Y, Omata M.: "Induction of proliferation-related signals by hepatitis C virus."(Okita K ed.) Growth, proliferation, and apoptosis in hepatocytes. (Springer-Verlag Tokyo). 81-98 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang Y, Kato N, Hoshida Y, Yoshida H, Taniguchi H, Goto T, Moriyaina M, Otsuka M, Shiina S, Shiratori Y, Ito Y, Omata M: "Interleukin-1β gene polymorphisms associated with hepatocellular carcinoma in hepatitis C virus infection."Hepatology. 37. 65-71 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Goto T, Kato N, Yoshida H, Otsuka M, Morlyama M, Shiratori Y, Koike K, Matsumura M, Omata M.: "Hepatitis B virus HBx and the large hepatitis Delta antigen synergistically activate the SRE-dependent pathway."J Infect Dis. 187. 820-828 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hara K, Ohe K, Kadowaki T, Kato N, Imai Y, Tokunaga K, Nagai R, Omata M.: "Establishment of a method of anonymization of DNA samples in genetic research."J Hum Genet. 48. 327-330 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Taniguchi H, Kato N, Otsuka M, Goto T, Yoshida H, Shiratori Y, Omata M.: "Hepatitis C virus core protein upregulates transforming growth factor-β1 transcription."J Med Virol. 2. 52-59 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wang Y, Kato N, Hoshida Y, Otsuka M, Taniguchi H, Moriyama M, Shiina S, Kawabe T, Ito YM, Omata M.: "UDP-glucournosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma in Japanese patients with hepatitis C virus infection."Clin Cancer Res. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hara K, Kato N, et al.: "Establishment of a method of anonymization of DNA samples in genetic research."J Hum Genet. 48. 327-330 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Otsuka M, Kato N, et al.: "Comparing gene expression profiles in human liver, gastric, and pancreatic tissues using full-length-enriched cDNA libraries."Hepatol Res. 27. 76-82 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Goto T, Kato N, et al.: "Hepatitis B virus HBx and the large hepatitis Delta antigen synergistically activate the SRE-dependent pathway."J Infect Dis. 187. 820-828 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanda T, Kato N, et al.: "Hepatitis A virus VP3 may activate serum response element associated transcription."Scand J Gastroenterol. 38. 307-313 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wang Y, Kato N, et al.: "UDP-glucuronosyltransferase lA7 genetic polymorphisms are associated with hepatocellular carcinoma in Japanese patients with hepatitis C virus infection."Clin Cancer Res. 10(in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Otsuka M, Kato N, et al.: "Signals Induced by HCV proteins. In : Hepatitis C Virus/Oxidative Stress and Liver Disease"Okita K ed., Springer-Verlag Tokyo. 32-47 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wang Y et al.: "Interleukin-1β gene polymorphisms associated with nepatocellular carcinoma in hepattes C virus infection"Hepatology. 37. 65-71 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Lan KH et al.: "HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis"Oncogene. 21. 4801-4811 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato J et al.: "Hepatitis c vivus NS4A and NS4B proteins suppress translation in vivo"J Med Virol. 66. 187-199 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Otsuka M et al.: "Hepatitis C virus core protein inhibits apoptosis via enhanced Bcl-x_L expression"Virology. 296. 84-93 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Otsuka M et al.: "Differential cellular gene expression induced by hepatitis B and C viruses"Biophys Biochem Res Commun. 300. 443-447 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Moriyama M et al.: "Relevance network between chewosensitivity and transcviptome in human hepatoma cells"Mol Cancer Ther. 2. 199-205 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kato N et al.: "Induction of proliferation-related siguals by hepatitis C Nirus, in : Grouth, proliferotion, and apoptosis in hepatocytes"Springer-Verlag Tokyo. 81-98 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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