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がん発症前高リスクに関わるがん体質遺伝素因の実体解明と試行的コホート解析

Research Project

Project/Area Number 18014017
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionOkayama University

Principal Investigator

清水 憲二  Okayama University, 大学院・医歯(薬)学総合研究科, 教授 (10037286)

Co-Investigator(Kenkyū-buntansha) 大内田 守  岡山大学, 大学院・医歯薬学総合研究科, 准教授 (80213635)
松原 長秀  岡山大学, 医学部・歯学部附属病院, 助手 (70314672)
小出 典男  岡山大学, 大学院・医歯薬学総合研究科, 教授 (20142333)
堺 明子  岡山大学, 大学院・医歯薬学総合研究科, 助教 (60205698)
伊藤 佐智夫  岡山大学, 大学院・医歯薬学総合研究科, 助教 (30335624)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2007: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2006: ¥5,500,000 (Direct Cost: ¥5,500,000)
Keywords癌発症危険度 / 癌体質遺伝 / 遺伝的多型 / ミスセンス1塩基多型 / リスク遺伝子型重複 / 癌分子疫学 / がん予防 / 早期発見診断 / がん体質遺伝 / 1塩基多型 / 肺がん / 大腸がん / 食道がん / 胃がん / 頭頸部がん / 疾患コホート
Research Abstract

本研究は、日本人の肺癌、頭頸部癌、大腸癌、食道癌、胃癌、膵臓癌、乳癌、前立腺癌における「発がんのリスク関わる遺伝子多型」を広汎に検索したものである。これまでに計225遺伝子、約270 SNPを解析した結果、有意差をもって上記の癌の発癌リスクに関わるミスセンスSNPを42遺伝子で計47種発見した(高リスク:34種、保護的SNP:13種)。42遺伝子にはDNA修復遺伝子、癌抑制遺伝子、物質代謝遺伝子、染色体分配遺伝子、細胞接着遺伝子等が含まれる。これらのms-SNPの多くは複数種の癌に関係し、多いものでは約8割の癌種に影響していた。上記のうち38 SNPの発癌リスクとの相関は、本研究で初めて示されたものである。
特筆すべきことは、本研究では対照健常人(約450検体)、癌患者(約1,300検体)共にほぼ全てのSNPを解析し、それらの重複のデータを得たことである。上記のうち、99%信頼区間も有意であった20遺伝子の24 SNPについて、癌種毎に関係する4〜7 SNPの個人別重複を数値化したところ、高リズクSNP数から保護的SNP数を差し引いた数値が上位20%に属する個人の割合は健常人で約4〜20%、癌患者で20〜60%を占めた。統計学的には、肺癌、大腸癌、食道癌についてはいずれもP値が10^<-10>〜10^<-16>、その他の癌では10^<-5>〜10^<-6>を示し、高い信頼性を示した。これらのグループの集団内発癌寄与率(PAR)は平均50%を占め、遺伝的リスクの過半を説明できることが判明した。さらに、我々は日本人の癌の約7割を占める肺癌、頭頸部癌、大腸癌、食道癌、胃癌、膵臓癌、乳癌、前立腺癌の各々について、約75%の低リスク群、25%の高リスク群、0.5-1.5%の超高リスク群を分別できる系を構築した。今後この系を前向きコホート研究で実証できれば、癌の予防と早期発見に革新的進展が実現できると期待される。

Report

(2 results)
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (42 results)

All 2008 2007 2006

All Journal Article (21 results) (of which Peer Reviewed: 11 results) Presentation (18 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] The association between RAD 18 Arg302Gln polymorphism and the risk of human non-small-cell lung cancer2008

    • Author(s)
      Kanzaki H., ほか
    • Journal Title

      J. Cancer Res. Clin. Oncol. 134

      Pages: 211-217

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Down-regulation of ING3 mRNA Eχpression predicts poor prognosis in head and neck cancer2008

    • Author(s)
      Gunduz M., ほか
    • Journal Title

      Cancer Science 99

      Pages: 531-538

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased expression of the SIN3A gene. a candidate tumor suppressor, located at the prevalent allelic loss region 15q23 in non-small cell lung cancer2008

    • Author(s)
      Suzuki H., ほか
    • Journal Title

      Lung Cancer 59

      Pages: 24-31

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased DOI-induced wet-dog shakes in adrenocorticotropic hormone-treated rats are not affected by chronic imipramine treatment: possible Involvement of enhanced 5-HT2A-receDtor exoression in frontal cortex2008

    • Author(s)
      Kitamura Y., ほか
    • Journal Title

      J. Pharmacol. Sci. 106

      Pages: 100-106

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fine deletion mapping of chromosome 2q21-37 shows three preferentially deletedregions in oral cancer2007

    • Author(s)
      Cengiz B., ほか
    • Journal Title

      Oral Oncol. 43

      Pages: 241-247

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oesophageal squamous cell cancer may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa2007

    • Author(s)
      Ishii T., ほか
    • Journal Title

      Gut 56

      Pages: 13-19

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Singfe nucleotide polymorphism in the RAD 18 gene and risk of colorectal cancer in Japanese population2007

    • Author(s)
      Kanzaki H., ほか
    • Journal Title

      Oncology Rep. 18

      Pages: 1171-1175

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss or down-regulation of HLA class l expression at the allelic level in freshly isolated leukemic blasts2007

    • Author(s)
      Masuda K., ほか
    • Journal Title

      Cancer Science 98

      Pages: 102-108

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comprehensive loss of heterozygosity analysis and identification of a novel hotspot at 3p21 in salivary gland neoplasms2007

    • Author(s)
      Honjo N., ほか
    • Journal Title

      Otolaryngol Head Neck Surg. 137

      Pages: 1191-1225

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of epidermal growth factor receptor gene status on gefitinib-treated Japanese patients with non-sraall-cell lung cancer2007

    • Author(s)
      lohihara S., ほか
    • Journal Title

      Int. J. Cancer 120

      Pages: 1239-1239

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] T75M-KCNJ2 mutation causing Andersen-Tawil syndrome enhances inward rectification by changing Mg2+ sensitivity2007

    • Author(s)
      Tani Y., ほか
    • Journal Title

      J. Mol. Cell. Cardiol. 43

      Pages: 187-196

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fine deletion mapping of chromosome 2q21-37 shows three preferentially deleted regions in oral cancer.2007

    • Author(s)
      Cengiz B, ほか
    • Journal Title

      Oral Oncol. 43

      Pages: 241-247

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Oesophageal squamous cell cancer may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa.2007

    • Author(s)
      Ishii T, ほか
    • Journal Title

      Gut 56

      Pages: 13-19

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Loss or down-regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts.2007

    • Author(s)
      Masuda K, ほか
    • Journal Title

      Cancer Sci. (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of a candidate tumor suppressor gene RHOBTB1 located at a novel allelic loss region 10q21 in head and neck cancer.2006

    • Author(s)
      Beder LB, ほか
    • Journal Title

      J.Cancer Res.Clin.Oncol. 132

      Pages: 19-27

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Single nucleotide polymorphism at codon 133 of the RASSF1 gene is preferentially associated with human lung adenocarcinoma risk.2006

    • Author(s)
      Kanzaki H, ほか
    • Journal Title

      Cancer Lett 238

      Pages: 128-134

    • Related Report
      2006 Annual Research Report
  • [Journal Article] EP2/EP4-mediated suppression of antigen-specific human T cell responses by prostaglandin E2.2006

    • Author(s)
      Okano M, ほか
    • Journal Title

      Immunology 118

      Pages: 343-352

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population.2006

    • Author(s)
      Kanzaki H, ほか
    • Journal Title

      Int J.Mol Med. 18

      Pages: 279-284

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Multiple splicing variants of Naf1/ABIN-1 transcripts and their alterations in hematopoietic tumors.2006

    • Author(s)
      Shiote Y, ほか
    • Journal Title

      Int J.Mol Med. 18

      Pages: 917-923

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Role of prostaglandin D2 and E2 terminal synthases in chronic rhinosinusitis.2006

    • Author(s)
      Okano M, ほか
    • Journal Title

      Clin Exp Allergy. 36

      Pages: 1028-1038

    • Related Report
      2006 Annual Research Report
  • [Journal Article] High frequent allelic loss of chromosome 6q16-23 in osteosarcoma : Involvement of cyclin C in osteosarcoma.2006

    • Author(s)
      Ohata N, ほか
    • Journal Title

      Int J.Mol Med. 18

      Pages: 1153-1158

    • Related Report
      2006 Annual Research Report
  • [Presentation] ミスセンスSNP34種の多重解析によるヒトがん発症危険度の統合的予測2007

    • Author(s)
      清水 憲二, ほか
    • Organizer
      がん予防大会in TOKYO 2007
    • Place of Presentation
      東京
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] RAD18遺伝子多梨と肺癌発症リスクの関連2007

    • Author(s)
      神崎 浩孝, ほか
    • Organizer
      がん予防大会in TOKYO 2007
    • Place of Presentation
      東京
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] RASSF6遺伝子のSNPと各種癌の発癌リスクとの関係2007

    • Author(s)
      戸田 恵奈, ほか
    • Organizer
      がん予防大会in TOKYO 2007
    • Place of Presentation
      東京
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] PTPRJ遺伝子のSNPと各種癌の発癌リスクとの関係2007

    • Author(s)
      三田 雄一郎, ほか
    • Organizer
      がん予防大会in TOKYO 2007
    • Place of Presentation
      東京
    • Year and Date
      2007-07-13
    • Related Report
      2007 Annual Research Report
  • [Presentation] Association of the RAD 18 gene Arg302Gln polymorphism with human non-small-cell lungcancer risk.2007

    • Author(s)
      Hirotaka Kanzaki., ほか
    • Organizer
      98th Annual Meeting of American Association for Cancer Research
    • Place of Presentation
      Los Angels, USA
    • Related Report
      2007 Annual Research Report
  • [Presentation] Proteome analysis of invasion-related proteins in malignant gliomas2007

    • Author(s)
      Hirotaka Kanzaki, ほか
    • Organizer
      HUPO. 6th Annual World Congress.
    • Place of Presentation
      Seoul, KOREA
    • Related Report
      2007 Annual Research Report
  • [Presentation] グリオーマ浸潤規定タンパクのプロテオミクス解析2007

    • Author(s)
      丸尾 智子, ほか
    • Organizer
      第8回 分子脳神経外科学会
    • Place of Presentation
      神戸
    • Related Report
      2007 Annual Research Report
  • [Presentation] IPG StripGelを用いた2次元電気泳動におけるspot検出効率とmatching rateの向上2007

    • Author(s)
      神崎浩孝、ほか
    • Organizer
      日本ヒトプロテオーム機構第5回大会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] 癌関連遺伝子におけるSNPと癌発症リスクの関連:RAD18遺伝子と非小細胞肺癌2007

    • Author(s)
      神崎浩孝、ほか
    • Organizer
      科学研究費補助金「特定領域」・がん研究に係わる特定領域研究・若手研究者ワークショップ
    • Place of Presentation
      長野
    • Related Report
      2007 Annual Research Report
  • [Presentation] 悪性グリオーマの浸潤に関わるタンパクのプロテオミクス解析による同定2007

    • Author(s)
      丸尾智子、ほか
    • Organizer
      第66回日本脳神経外科学会総会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] 日本人におけるRAD18遺伝子多型と肺癌及び大腸癌発症リスクの関連2007

    • Author(s)
      神崎浩孝、ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 成人T細胞白血病/リンパ腫(ATLPにおける特異的DNAメチル化と病態・臨床症状との相関2007

    • Author(s)
      佐藤妃映、ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 骨肉腫における6q16-23の高頻度染色体欠失の研究2007

    • Author(s)
      大畑範英、ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular analysis of ING3 and ING4 and their prognostic role in head and neck cancers2007

    • Author(s)
      GunduzE,ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Molecular and histopathological analysis of the EGFR-Ras-RAF pathway in head and neck squamous cell carcinomas2007

    • Author(s)
      Gunduz M, ほか
    • Organizer
      第66回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 滑膜肉腫特異的転座型融合蛋白SS18-SSX及びSS18、SSX蛋白の細胞内局在の解析2007

    • Author(s)
      米田泰史、ほか
    • Organizer
      第22回日本整形外科学会基礎学術集会
    • Place of Presentation
      浜松
    • Related Report
      2007 Annual Research Report
  • [Presentation] 悪性グリオーマの浸潤に関するプロテオーム解析2007

    • Author(s)
      神崎 浩孝, ほか
    • Organizer
      BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会合同大会)
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 骨肉腫における染色体6q16-23の高頻度欠失2007

    • Author(s)
      大内 田守, ほか
    • Organizer
      BMB2007(第30回日本分子生物学会年会・第80回日本生化学会大会合同大会)
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Book] Gene Silencing : New Research2006

    • Author(s)
      Oka Takashi
    • Total Pages
      201
    • Publisher
      Nova Science Publishers, Inc.
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 癌の発症危険率を予測する方法2007

    • Inventor(s)
      清水 憲二
    • Industrial Property Rights Holder
      国立大学法人岡山大学
    • Industrial Property Number
      2007-193981
    • Filing Date
      2007-07-26
    • Related Report
      2007 Annual Research Report
  • [Patent(Industrial Property Rights)] 癌の発症危険率を予測する方法2006

    • Inventor(s)
      清水憲二
    • Industrial Property Rights Holder
      岡山大学
    • Industrial Property Number
      2006-204620
    • Filing Date
      2006-07-27
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2018-03-28  

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