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がん発症前高リスクに関わるがん体質遺伝診断法の確立

Research Project

Project/Area Number 20014013
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) 豊岡 伸一  岡山大学, 大学病院, 助教 (30397880)
松原 長秀  岡山大学, 医学部・歯学部附属病院, 助教 (70314672)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2009: ¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2008: ¥7,300,000 (Direct Cost: ¥7,300,000)
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 / 癌の早期発見診断 / コホート研究 / がん予防
Research Abstract

癌種の追加:これまで解析してきた癌種の検体数を追加し、さらに婦人科癌(子宮頸癌,子宮体癌,卵巣癌),尿路系腫瘍(膀胱癌,腎癌,尿路癌)、膵胆肝癌(胆道癌、肝癌)、なども収集して,累計2,500検体が集積した。また、再現性試験用の約2,000検体を共同研究機関から提供頂いた。婦人科癌についてはのべ22遺伝子多型の関与が判明した。
地域,年齢合致対照検体の確保:これまでに岡山大学病院から収集された癌患者検体の厳密な統計学的検討を行うために,地域と性比,年齢層が一致した対照群が必要である。今年度,岡山市内のJ健康管理センターと提携し、継続的な人間ドック受診者の中から,癌年齢に達した1,000件の検体を確保できた。今までに収集した岡山市内の約500名の検体と合わせて,計1,500件の対照検体を用い,約40種類のSNPと9種の癌の発症リスクとの関連を、より厳密な統計学的解析で再確認できた。遺伝子解析の結果、これら約1,500名の健常人のうち計220名(15%)は9種の何れかの癌の発症リスクが極めて高いと予測された。
同一遺伝子内の複数の遺伝子多型の組み合わせと発癌リスクの相関:本年度の特筆すべき成果は複数SNP複合遺伝子型と癌のリスクに関する新知見である。PTPRJ遺伝子はマウスの大腸癌感受性遺伝子であるが,ヒトでも大腸癌の発症に密接に関わることを初めて実証した。特に,本遺伝子の2種のms-SNPについて、健常人では極めて稀な複合遺伝子型が癌患者では10%以上あり,オッズ比が50以上に達することが判明した。このリスクは高浸透率の遺伝性腫瘍原因遺伝子変異に匹敵する。これはタンパク質中の2個のアミノ酸が特別なアミノ酸の組み合わせになると発癌リスクが飛躍的に増大するという,興味深い発見である。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (53 results)

All 2010 2009 2008 Other

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (28 results) Remarks (1 results)

  • [Journal Article] Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers.2010

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

      J Cancer Res Clin Oncol. 136

      Pages: 249-259

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multi-step aberrant CpG island hyper-methylation is associated with the progression of adult T-cell leukemia/lymphoma.2010

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

      Am J Pathol. 176

      Pages: 402-415

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent allelic loss of Dkk-1 locus (10q11.2) is related with low distant metastasis and better prognosis in head and neck squamous cell carcinomas.2010

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

      Cancer Invest. 28

      Pages: 103-110

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fine deletion analysis of 1p36 chromosomal region in oral squamous cell carcinomas.2009

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

      J Oral Pathol Med 38

      Pages: 94-98

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Down-regulation of TESTIN and its association with previous cancer history and poor survival in head and neck squamous cell carcinomas.2009

    • Author(s)
      Gunduz E, ほか
    • Journal Title

      Arch Otolaryngol Head Neck Surg. 135

      Pages: 254-260

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent deletion of ING2 locus at 4q35.1 associates with advanced tumor stage in head and neck squamous cell carcinoma.2009

    • Author(s)
      Borkosky SS, ほか
    • Journal Title

      J Cancer Res Clin Oncol. 135

      Pages: 703-713

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] T-lymphocyte maturation-associated protein gene as a candidate metastasis suppressor for head' and neck squamous cell carcinomas.2009

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

      Cancer Sci. 100

      Pages: 873-880

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased mRNA expression of ADAMTS metalloproteinases in metastatic foci of head and neck cancer.2009

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

      Head Neck. 31

      Pages: 793-801

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Frequent Allelic Loss of Dkk-1 Locus (10q11.2) is Related with Low Distant Metastasis and Better Prognosis in Head and Neck Squamous Cell Carcinomas.2009

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

      Cancer Invest.

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MET gene amplification or EGFR mutation activate MET in lung cancers untreated with EGFR tyrosine kinase inhibitors.2009

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

      Int J Cancer 124

      Pages: 1778-1784

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] REIC/Dkk-3 stable transfection reduces the malignant phenotype of mouse prostate cancer RM9 cells.2009

    • Author(s)
      Chen J, ほか
    • Journal Title

      Int, J, Mol, Med. 24

      Pages: 789-794

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Accumulation of aberrant CpG hypermethylation by Helicobacter pylori infection promotes development and progression of gastric MALT lymphoma.2009

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

      Int J Oncol. 35

      Pages: 547-557

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of heterozygosity at the 9p21-24 region and identification of BRM as a candidate tumor suppressor gene in head and neck squamous cell carcinoma.2009

    • Author(s)
      Gunduz E, ほか
    • Journal Title

      Cancer Invest. 27

      Pages: 661-668

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression and Mutation Analysis of Her2 in Head and Neck Squamous Cell Carcinoma.2009

    • Author(s)
      Ali MA, ほか
    • Journal Title

      Cancer Invest.

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [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
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Down-regulation of ING3 mRNA Expression predicts poor prognosis in head and neck cancer2008

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

      Cancer Sci. 99

      Pages: 531-538

    • Related Report
      2008 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
      2008 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-receptor expression in frontal cortex2008

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

      J. Pharmacol. Sci. 106

      Pages: 100-106

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion at Dickkopf (dkk)-3 locus (11p15.2) is related with lower lymph node metastasis and better prognosis in head and neck squamous cell carcinomas2008

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

      Oncol Res 17

      Pages: 273-282

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lack of B-RAF mutations in head and neck squamous cell carcinoma2008

    • Author(s)
      Al Sheikh Ali M., ほか
    • Journal Title

      Folia Biol 54

      Pages: 157-161

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression and mutation analysis of epidermal growth factor receptor in head and neck squamous cell carcinoma2008

    • Author(s)
      Sheikh Ali MA., ほか
    • Journal Title

      Cancer Sci 99

      Pages: 1589-1594

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of heterozygosity at chromosome 14q is associated with poor prognosis in head and neck squamous cell carcinomas2008

    • Author(s)
      Pehlivan D., ほか
    • Journal Title

      J Cancer Res Clin Oncol. 134

      Pages: 1267-1276

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Deletion mapping of chromosome 4q22-35 and identification of four frequently deleted regions in head and neck cancers2008

    • Author(s)
      Cetin E., ほか
    • Journal Title

      Neoplasma 55

      Pages: 299-304

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of EphA2 in head and neck squamous cell carcinoma : mRNA expression, loss of heterozygosity and immunohistochemical studies2008

    • Author(s)
      Rivera RS., ほか
    • Journal Title

      Oncol Rep. 19

      Pages: 1079-1084

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Multiple Polymorphisms of the MMP Family Genes are Associated with Colorectal Cancer Risk2010

    • Author(s)
      三田雄一郎, ほか
    • Organizer
      国際疫学西太平洋地域学術会議兼 第20回日本疫学会学術総会
    • Place of Presentation
      埼玉
    • Related Report
      2009 Annual Research Report
  • [Presentation] がん体質遺伝について2009

    • Author(s)
      清水憲二
    • Organizer
      第97回日本泌尿器科学会総会 特別講演
    • Place of Presentation
      岡山
    • Year and Date
      2009-04-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] Identification of novel target protein for miR-17-92 cluster by proteomic analysis.2009

    • Author(s)
      Hirotaka Kanzaki, ほか
    • Organizer
      100th AACR Annual Meeting
    • Place of Presentation
      Denver, CA, USA
    • Related Report
      2009 Annual Research Report
  • [Presentation] Proteomic analysis of lung cancer cell lines aimed to identify novel target proteins for miR-17-92.2009

    • Author(s)
      HirotakaKanzaki, ほか
    • Organizer
      HUPO 8th Annual World Congress
    • Place of Presentation
      Toronto, CANADA
    • Related Report
      2009 Annual Research Report
  • [Presentation] MMP Family遺伝子の10種のSNPsと非小細胞肺癌発症リスクとの関連解析2009

    • Author(s)
      三田雄一郎, ほか
    • Organizer
      がん予防大会 2009(第10回 日本がん分子疫学研究会ほか)
    • Place of Presentation
      名古屋
    • Related Report
      2009 Annual Research Report
  • [Presentation] miR-17-92 clusterの肺癌における新規標的タンパク質の同定を目的としたプロテオーム解析2009

    • Author(s)
      神崎浩孝, ほか
    • Organizer
      日本ヒトプロテオーム機構(JHUPO)第7回大会
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] プロテオーム解析による肺癌におけるmiR-17-92の直接的な新規標的タンパク質の同定2009

    • Author(s)
      神崎浩孝, ほか
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] 乳癌におけるmiRNA clusterの新規標的タンパク質の検討2009

    • Author(s)
      大内田守, ほか
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] TP53遺伝子多型と膵臓癌発症リスク2009

    • Author(s)
      園山隆之, ほか
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] 成人T細胞白血病/リンパ腫(ATLL)における異常DNAメチルDNAメチル化と病態との相関2009

    • Author(s)
      佐藤妃映, ほか
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] ゲフィチニブ感受性および耐性細胞株の上皮成長因子受容体に対するMicro-RNA 7による抑制効果2009

    • Author(s)
      頼冠名, ほか
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] 日本人におけるMMP9遺伝子多型と大腸癌発症リスクとの関係2009

    • Author(s)
      三田雄一郎, ほか
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] Identification of novel target of miR- 17-92 cluster by proteomic analysis2009

    • Author(s)
      神崎浩孝, ほか
    • Organizer
      BMB2009(第32回日本分子生物学会年会・第82回日本生化学会大会合同大会)
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] 慢性疼痛の遺伝子治療薬の開発2009

    • Author(s)
      大内田守, ほか
    • Organizer
      BMB2009(第32回日本分子生物学会年会・第82回日本生化学会大会合同大会)
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] MicroRNA expression profiling in human tumors.2009

    • Author(s)
      伊藤佐智夫, ほか
    • Organizer
      BMB2009(第32回日本分子生物学会年会・第82回日本生化学会大会合同大会)
    • Place of Presentation
      横浜
    • Related Report
      2009 Annual Research Report
  • [Presentation] PTP Family遺伝子のSNPsと各種がんの発症リスクとの関係2008

    • Author(s)
      三田雄一郎
    • Organizer
      がん特定領域研究若手研究者ワークショップ
    • Place of Presentation
      アートランドホテル蓼科
    • Related Report
      2008 Annual Research Report
  • [Presentation] Association of aberrant DNA methylation with a poor prognosis in Adult T cell leukemia/lymphoma2008

    • Author(s)
      佐藤妃映, ほか
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] 骨肉腫患者における葉酸代謝関連遺伝子の一塩基多型の検討2008

    • Author(s)
      森本裕樹, ほか
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] ゲフィチニプ未使用肺癌におけるMET遺伝子増幅について2008

    • Author(s)
      久保孝文, ほか
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] 頭頸部癌における分子予後因子としてING3遺伝子の検討2008

    • Author(s)
      Mehmet Gunduz, ほか
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] 日本人の前立腺がん発症に関与する複数のミスセンスSNPの解析2008

    • Author(s)
      堺明子, ほか
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] 日本人におけるPTPN13遺伝子多型と各種癌の発症リスクとの関係2008

    • Author(s)
      三田雄一郎, ほか
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] 日本における主要な8種のがんの易罹患性に関与する48ミズセンスSNPの総合的解析2008

    • Author(s)
      清水憲二, ほか
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Related Report
      2008 Annual Research Report
  • [Presentation] Rasmussen encephalitis associated with SCN1A mutation2008

    • Author(s)
      Mamoru Ouchida, ほか
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] MMP Family遺伝子のSNPsと日本人における非小細胞肺癌発症リスクとの関連2008

    • Author(s)
      三田雄一郎, ほか
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] MicroRNA expression profiling in human esophageal cancer2008

    • Author(s)
      Sachio lto, ほか
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] プロテオミクス解析によるmiRNA clusterの新規標的タンパク質の探索2008

    • Author(s)
      神崎浩孝, ほか
    • Organizer
      第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2008 Annual Research Report
  • [Presentation] Comprehensive analyses of 15missense-SNPs in 12genes involved in non-small cell lung cancer risk in Japanese2008

    • Author(s)
      Kenji Shimizu
    • Organizer
      The 13th Japan-Korea Cancer Research Workshop
    • Place of Presentation
      Daejeon, Korea
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://genet1.med.okayama-u.ac.jp/

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2018-03-28  

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