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Molecular pathological study of individual predisposition to gastric cancer

Research Project

Project/Area Number 15390125
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

SUGIMURA Haruhiko  Hamamatsu University School of Medicine, 1st Department of pathology, Professor, 医学部, 教授 (00196742)

Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2005: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2004: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2003: ¥5,500,000 (Direct Cost: ¥5,500,000)
Keywordsgastric cancer / molecular epidemiology / genetic predisposition / genetic polymorphism / oxidative DNA damage / multiple gastric cancer / GI tract cancer / FISH / 胃癌 / 胃癌感受性 / 胃癌家系 / ハプロタイプ / Peutz-Jeghers症候群 / CDH1 / 家族性胃癌 / 遺伝統計 / ミニサテライト / 連鎖解析 / Peutx-Jeghers症候群 / 染色体不安定性 / 家族性腫瘍 / 多発胃癌 / 遺伝的感受性 / 遺伝子修復 / FISH
Research Abstract

The following results were obtained during the above period.
1.Mis-sense germline mutation of CDH1 in Japanese familial gastric cancer subjects.
2.The investigator clarified that OGG1 polymorphism modified the life style dependent risk of upper GI tract cancer.
3.A new method to detect chromosomal instability in pathology archives of gastric cancer was developed. Using this technique the investigator identified a particular feature of gastric cancer with family history, multiplicity, and particular histological type.
4.Repair genes such as NEIL1 and MYH were altered both in somatic and germline DNA of gastric cancer with/without family history of cancer. Newly identified polymorphism of MYH is shown to be clearly associated localization alteration.
5.A novel LKB1 mutation was identified in Peutz-Jeghers syndrome with gastric cancers.
6.Eph /EFN family genes were investigated in gastric and colorectal cancers. Germline and somatic mutation searches were performed expecting the situation for familial prostate and familial hyperplastic colorectal polyposis. Loss of heterozygosity of EPHB2 in colorectal cancer was demonstrated, and EPHA2 expression in gastric cancer was documented. EFNA1 suppressed the growth of EFHA2 expressing gastric cancer cell lines. These genes were demonstrated to interact with Tiam1, which is localized in the candidate area of gastric cancer predispostiion according to sib-pair analyses.
7.Extension to searches for germline mutations of candidate genes in familial gastric cancer cases.
8.A novel polymorphism in KLK12 was found in gastric cancer patients and alteration in gastric cancer was described.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (27 results)

All 2006 2005 2004 Other

All Journal Article (20 results) Publications (7 results)

  • [Journal Article] Mdm2-mediated pRB downregulation is involved in carcinogenesis in a p53-independent manner2006

    • Author(s)
      Miwa S, Sugimura H et al.
    • Journal Title

      Biochem Biophys Res Commun 340(1)

      Pages: 54-61

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation.2005

    • Author(s)
      Uchida C, Sugimura H, et al.
    • Journal Title

      EMBO J. 24

      Pages: 160-169

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A full genome scan for gastric cancer.2005

    • Author(s)
      Aoki M, Sugimura H, et al.
    • Journal Title

      J Med Genet. 42

      Pages: 83-87

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Over-expression of MUC13 Is Associated with Intestinal Type Gastric Cancer.2005

    • Author(s)
      Shimamura T, Sugimura H, et al.
    • Journal Title

      Cancer Sci. 96(5)

      Pages: 265-273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Downregulation of EphA7 by hypermethylation in colorectal cancer.2005

    • Author(s)
      Wang J, Sugimura H, et al.
    • Journal Title

      Oncogene. 24

      Pages: 5637-5647

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Pilot study of arbitrarily primed PCR-single stranded DNA conformation polymorphism analysis for screening genetic polymorphisms related to specific phenotypes.2005

    • Author(s)
      Maekawa M, Sugimura H, et al.
    • Journal Title

      Clin.Chimi.Acta. 355

      Pages: 181-184

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Suppressive effect of epigallocatechin gallate (EGCg) on DNA methylation in mice : Detection by methylation sensitive restriction endonuclease digestion and PCR.2005

    • Author(s)
      Yamada H, Sugimura H, et al.
    • Journal Title

      J.Food, Agriculture & Environment. 3

      Pages: 73-76

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Simultaneous Imaging of Membrane Antigen and the Corresponding Chromosomal Locus in Pathology Archives.2005

    • Author(s)
      Igarashi H, Sugimura H, et al.
    • Journal Title

      Pathol Int. 55

      Pages: 753-756

    • NAID

      10017126345

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection.2005

    • Author(s)
      Sugimoto M, Sugimura H, et al.
    • Journal Title

      Aliment Pharmacol Ther. 22

      Pages: 1033-1140

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Poor metabolizer genotype status of CYP2C19 is a risk factor for developing gastric cancer in Japanese patients with Helicobacter pylori infection2005

    • Author(s)
      Sugimoto M, Sugimura H et al.
    • Journal Title

      Aliment Pharmacol Ther. 22(10)

      Pages: 1033-1040

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation.2005

    • Author(s)
      Uchida C, Sugimura H et al.
    • Journal Title

      EMBO J 24

      Pages: 160-169

    • Related Report
      2005 Annual Research Report
  • [Journal Article] EPHA2/EFNA1 expression in human gastric cancer2005

    • Author(s)
      Nakamura R, Sugimura H et al.
    • Journal Title

      Cancer Science 96

      Pages: 42-47

    • NAID

      10015523911

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel STK11 germline mutation in two siblings with Peutz-Jeghers syndrome complicated by primary gastric cancer.2005

    • Author(s)
      Shinmura K, Sugimura H et al.
    • Journal Title

      Clinical Genetics 67

      Pages: 81-86

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A full genome scan for gastric cancer.2005

    • Author(s)
      Aoki M, Sugimura H et al.
    • Journal Title

      J.Med.Genet 42

      Pages: 83-87

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Amplicons on human chromosome 11q are located in the early/late-switch regions of replication timing2004

    • Author(s)
      Watanabe Y, Sugimura H et al.
    • Journal Title

      Genomics 84

      Pages: 796-805

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Methylation of mitochondrial DNA is not a useful marker for cancer detection.2004

    • Author(s)
      Maekawa M, Sugimura H et al.
    • Journal Title

      Clin Chem 50

      Pages: 1480-1481

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Potential usefulness of detecting cyclooxygenase 2 messenger RNA in feces for colorectal cancer screening2004

    • Author(s)
      Kanaoka S, Sugimura H et al.
    • Journal Title

      Grastroenterology 127

      Pages: 422-427

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel splice-site variant of the base excision repair gene MYH is associated with production of an aberrant mRNA transcript encoding a truncated MYH protein not localized in the nucleus.2004

    • Author(s)
      Tao H, Sugimura H et al.
    • Journal Title

      Carcinogenesis 25

      Pages: 1859-1866

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Polymorphisms in thymidylate synthase and methylenetetrahydrofolate reductase genes and the susceptibility to esophageal and stomach cancer with smoking2004

    • Author(s)
      Gao CM, Sugimura H et al.
    • Journal Title

      Asian Pac J Cancer Prev 5

      Pages: 133-138

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Enhanced Mdm2 activity inhibits pRB function via ubiquitin-dependent degradation2004

    • Author(s)
      Uchida C, Sugimura H et al.
    • Journal Title

      EMBO J 24

      Pages: 160-169

    • Related Report
      2004 Annual Research Report
  • [Publications] Wang Y, Sugimura, H et al.: "Ile-Leu substitution (I415L) in germ line E-cadherin gene(CDH1) in a Japanese familial gastric cancer"JJCO. 33. 17-20 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Otsuki Y, Sugimura H et al.: "Guanin nucleotide exchange factor, Tiam1, directly binds to c-Myc and interferes with c-Myc mediated apoptosis in Rat-1 fibroblasts."JBC. 278. 5132-5140 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanaka M, Sugimura H et al.: "Association of Dishevelled with Eph-tyrosine kinase receptor and ephrin mediates cell repulsion."EMBO J. 22. 847-858 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Vinies P, Sugimura H et al.: "CYP1A1 T3801 C polymorphism and lung cancer : a pooled analysis of 2451 cases and 3358 controls."Int J Cancer. 104. 650-657 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Le Marchant L, Sugimura H et al.: "Pooled analysis of the CYP1A1 exon 7polymorphism and lung cancer (United States)."Cancer Causes Control. 14. 339-346 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kitayama Y, Sugimura H: "Non-random chromosomal numerical abnormality predicting prognosis of gastric cancer, a retrospective study of 51 cases using pathology archives."Lab Invest. 83. 1311-1320 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 椙村春彦(分担): "分子予防環境医学"本の泉社. 760(420-427) (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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