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Molecular epidemiologic study of lung cancer on interaction between smoking and genetic factors

Research Project

Project/Area Number 17390175
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionKyushu University

Principal Investigator

KIYOHARA Chikako  Kyushu University, 大学院・医学研究院, 講師 (00169963)

Co-Investigator(Kenkyū-buntansha) NAKANISHI Yoichi  九州大学, 大学院・医学研究院, 教授 (20172356)
高山 浩一  九州大学, 大学院・医学研究院, 講師 (50274444)
堀内 孝彦  九州大学, 大学院・医学研究院, 准教授 (90219212)
三宅 吉博  福岡大学, 医学部, 准教授 (50330246)
Project Period (FY) 2005 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥15,910,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2007: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥5,400,000 (Direct Cost: ¥5,400,000)
Keywords社会医学 / 分子疫学 / 肺がん / 交互作用 / 国際共同研究 / 薬物代謝 / DNA除去修復 / 遺伝子多型
Research Abstract

本研究はInternational Lung Cancer Consortium(ILCCO)国際共同研究の一環として行われるものである。本学医学研究院等倫理委員会およびヒトゲノム・遺伝子解析倫理審査委員会の承認を得た後、本研究を開始した。症例と対照のDNAの収集も続けているが、医療情報部において連結匿名化を終えた対象者のDNAについての遺伝子解析を行った。網羅的な遺伝子解析は時間と費用を浪費するので、遺伝子解析の優先順位をつけるために、先に文献的な検討を行った。肺がんとDNA修復酵素の遺伝子多型、特にヌクレオチド除去修復遺伝子についてのメタ分析を行い(Kiyohara C, Yoshimasu K. Int J Med Sci 2007 ; 4 : 59-71)、ERCC2が肺がん発症感受性に重要な役割をしている事が分かった。また、肺がん発症高感受性群を特定できるかを検討した(Kiyohara C, et.al. Future Oncol. 2007 ; 3 : 617-627)。その結果、第一相薬物代謝に関わる遺伝子であるCYP1A1 T3801C多型、第二相薬物代謝に関わる遺伝子であるGSTM1 deletion多型とDNA除去修復に関わるERCC2 Lys751Gln多型の3つを組み合わせることにより、肺がん発症高感受性者を効率よく同定できる可能性が示された。事実、いずれか1つのリスクアレル遺伝子型を持つ場合のオッズ比は、単独効果とほぼ同じで1.61-2.02の範囲にあった。いずれか2つのリスクアレル遺伝子型を持つ場合のオッズ比は2.27-2.57の範囲にあった。3つのリスクアレル遺伝子型を持つ場合のオッズ比は5.94(95%信頼区間=2.77-12.7)であり、リスクアレルの累積により顕著な肺がんリスクの高まりが観察された。本研究の結果の一部(MTHFR遺伝子多型と肺がん)を筆頭発表者として第14回欧州がん会議(2007)において、また、分担発表者として2007年度アメリエがん学会のミニシンポジウムおいてDNA修復酵素遺伝子多型についての国際共同研究の成果(プール解析)を発表した。

Report

(5 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (19 results)

All 2009 2008 2007 2006

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (4 results) Book (5 results)

  • [Journal Article] Meta- and Pooled Analysis of GSTP1 and Lung Cancer : A HuGE-GSEC Review2009

    • Author(s)
      Cote ML, Kiyohara C, et al.
    • Journal Title

      American Journal of Epidemiology 169

      Pages: 802-814

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] International Lung Cancer Consortium : Pooled analysis of sequence variants in DNA repair and cell cycle control pathways2008

    • Author(s)
      Hung RJ, Kiyohara C et.al.
    • Journal Title

      Cancer Epidemiol Biomark Prev(International Lung Cancer Consortium) 17

      Pages: 3081-3089

    • Related Report
      2008 Final Research Report
  • [Journal Article] International Lung Cancer Consortium : Pooled analysis of sequence variants in DNA repair and cell cycle control pathways.2008

    • Author(s)
      Hung RJ, Kiyohara C, et al.
    • Journal Title

      Cancer Epidemiology Biomarkers and Prevention 17

      Pages: 3081-3089

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CYP1A1, GSTM1, and GSTT1 polymorphisms, smoking, and lung cancer risk in a pooled analysis among Asian populations.2008

    • Author(s)
      Lee KM, Kiyohara C, et al.
    • Journal Title

      Cancer Epidemiology Biomarkers and Prevention 17

      Pages: 1120-1126

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk : A meta-analysis2007

    • Author(s)
      Kiyohara C, Yoshimasu K.
    • Journal Title

      Int J Med Sci 4

      Pages: 59-71

    • Related Report
      2008 Final Research Report
  • [Journal Article] Lung cancer susceptibility : are we on our way to identifying a high-risk group?2007

    • Author(s)
      Kiyohara C, Yoshimasu K, Takayama K, Nakanishi Y
    • Journal Title

      Future Oncol 3

      Pages: 617-627

    • Related Report
      2008 Final Research Report
  • [Journal Article] Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk:A meta-analysis2007

    • Author(s)
      Kiyohara C, et. al.
    • Journal Title

      International Journal of Medical Sciences 4

      Pages: 59-71

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lung cancer susceptibility:are we on our way to identifying a high-risk group2007

    • Author(s)
      Kiyohara C, et. al.
    • Journal Title

      Future Oncology 3

      Pages: 617-627

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk : A meta-analysis2006

    • Author(s)
      Kiyohara C, Takayama K, Nakanishi Y.
    • Journal Title

      Lung Cancer 54

      Pages: 267-283

    • Related Report
      2008 Final Research Report
  • [Journal Article] Association of genetic polymorphisms in the base excision repair pathway with lung cancer risk : A meta-analysis.2006

    • Author(s)
      Chikako Kiyohara, et al.
    • Journal Title

      Lung Cancer 54

      Pages: 267-283

    • Related Report
      2006 Annual Research Report
  • [Presentation] MTHFR polymorphisms and lung cancer risk in a Japanese population2008

    • Author(s)
      Kiyohara C, Takayama K, Nakanishi Y
    • Organizer
      The 14th European Cancer Conference
    • Place of Presentation
      Barcelona, Spain
    • Related Report
      2008 Final Research Report
  • [Presentation] MTHFR polymorphisms and lung cancer risk in a Japanese population.2007

    • Author(s)
      Kiyohara C, et. al.
    • Organizer
      14th European Cancer Conference
    • Place of Presentation
      スペイン(バルセロナ)
    • Year and Date
      2007-09-27
    • Related Report
      2007 Annual Research Report
  • [Presentation] International lung cancer consortium:Pooled analysis of sequence variations in DNA repair pathway.2007

    • Author(s)
      Hung RJ, Kiyohara C, et. al.
    • Organizer
      American Association for Cancer Research Annual Meeting 2007
    • Place of Presentation
      アメリカ(ロサンゼルス)
    • Year and Date
      2007-04-17
    • Related Report
      2007 Annual Research Report
  • [Presentation] International Lung Cancer Consortium Investigators. International Lung Cancer Consortium : Pooled analysis of Sequence Variants in DNA Repair Pathway2007

    • Author(s)
      Hung RJ, Kiyohara C et al.
    • Organizer
      American Association for Cancer Research Annual Meeting 2007
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2008 Final Research Report
  • [Book] Nova Science Publishers Inc. NY, Chapter 1. Genetic predisposition to lung cancer(Genetic Predisposition to Disease : New Reseach. Bernard LE, Laurent MB(eds.))2008

    • Author(s)
      Kiyohara C, Yoshimasu, Takayama K, Nakanishi Y
    • Related Report
      2008 Final Research Report
  • [Book] Genetic predisposition to lung cancer. In : Genetic Predisposition to Disease : New Research(Editors : Louane E. Bernard Maelys B. Laurent)2008

    • Author(s)
      Kiyohara C, et al.
    • Publisher
      Nova Science Publishers Inc. NY
    • Related Report
      2008 Annual Research Report
  • [Book] Nova Science Publishers Inc. NY, DNA repair and lung cancer New Research on DNA Repair. Breehn R. Landseer(ed.))2007

    • Author(s)
      Kiyohara C, Takayama K, Nakanishi Y.
    • Publisher
      Chapter 2
    • Related Report
      2008 Final Research Report
  • [Book] Nova Science Publishers Inc. NY, Chapter 1. Environmental tobacco smoke and respiratory disease(Passive Smoking and Health Research. Nivek A. Joergensen (ed.))2006

    • Author(s)
      Kiyohara C, Inoue H, Nakanishi Y.
    • Publisher
      Chapter 1
    • Related Report
      2008 Final Research Report
  • [Book] Chapter 1. Environmental tobacco smoke and respiratory disease. pp1-pp41. In : Passive Smoking and Health Research.2006

    • Author(s)
      Chikako Kiyohara, et al.
    • Total Pages
      365
    • Publisher
      Nova Science Publishers Inc. NY
    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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