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がん関連遺伝子発現の個体差と宿主・環境要因に関する研究

Research Project

Project/Area Number 12218239
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionRadiation Effects Research Foundation (2001-2004)
Research Institute for Clinical Oncology, Saitama Cancer Center (2000)

Principal Investigator

中地 敬  財団法人放射線影響研究所, 放射線生物学/分子疫学部, 部長 (00142117)

Co-Investigator(Kenkyū-buntansha) 林 慎一  東北大学, 医学部保健学科検査技術科学専攻, 教授 (60144862)
菅沼 雅美  埼玉県立がんセンター, 研究室・主任研究員 (20196695)
末岡 榮三朗 (末岡 榮三郎 / 末岡 栄三朗)  佐賀大学, 医学部, 助教授 (00270603)
SHARP G・B  財団法人 放射線影響研究所, 疫学部, 副主任研究員
今井 一枝  財団法人 放射線影響研究所, 疫学部, 研究員 (80260230)
赤木 究  埼玉県立がんセンター, 研究所, 研究員 (30244114)
三宅 智  東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (00332346)
大倉 康男  埼玉県立がんセンター, 臨床病理部, 医長 (30312284)
Project Period (FY) 2000 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥169,100,000 (Direct Cost: ¥169,100,000)
Fiscal Year 2004: ¥33,700,000 (Direct Cost: ¥33,700,000)
Fiscal Year 2003: ¥34,400,000 (Direct Cost: ¥34,400,000)
Fiscal Year 2002: ¥34,000,000 (Direct Cost: ¥34,000,000)
Fiscal Year 2001: ¥33,000,000 (Direct Cost: ¥33,000,000)
Fiscal Year 2000: ¥34,000,000 (Direct Cost: ¥34,000,000)
KeywordsNK活性 / 遺伝子多型 / コーホート研究 / ピロリ菌 / 肺がん / 乳がん / NKG2D / がん予防 / Tip(TNF-α inducing protein) / hnRNP B1 / 前がん病変マーカー / 血清α_2-グロブリン / H. pylori / コホート研究 / 免疫 / H.pylori / エストロゲンレセプターα / hnRNP / EGCG / 発がんリスク / がん化学予防 / エストロゲンレセプター / 緑茶
Research Abstract

コーホート研究により、発がんの免疫的宿主防御であるNK活性に関与する遺伝的要因として、NK細胞の活性型受容体であるNKG2Dの遺伝子領域にNK活性と強く関連したハプロタイプブロックを見いだした。次に、コーホート内症例対照研究を行いNKG2Dハプロタイプの発がんリスクの評価を行った。コーホート内症例対照研究により、NK高活性に関連したハプロタイプの発がん相対危険が低いことを示した。すなわち、NK高活性に関連したアリールをhomozygousにもつHNK1/HNK1の人は、NK低活性に関連したアリールをhomozygousにもつLNK1/LNK1に比べ、オッズ比0.48(95%CI、0.24-0.95)の低い全がん罹患リスクを示した。これらの結果は、がん免疫予防の主たる対象となる高危険群の同定に有用であり、NK活性を代理マーカーとした新たながん予防の道を開くものと考える。コーホート研究と並行して、臓器別にがん予防に有用な生体マーカーの研究を進めた。H. pyloriが遊離する新しい発がん因子Tipαはホモダイマーが活性型であり、Tipαのダイマー形成阻害を戦略とした新しい胃がん予防を目指す。緑茶ポリフェノールEGCGとsulindac、all-trans-retinoic acidあるいはcelecoxibを併用すると、GADD153を強く誘導し、相乗的に肺がん細胞のアポトーシスを誘導する。乳がんのエストロゲン応答解析用cDNAチップを用いて、HDAC6、IGFBP4、EGR3の乳がんの新規予後因子を見出した。hnRNP B1は肺発がん早期から高発現しており、肺がん患者の血漿hnRNP B1 mRNA量は、非がん群より高かった。迅速定量法の開発により、肺がん検診および前がん病変のマーカーとしての応用を検討している。

Report

(5 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (43 results)

All 2005 2004 Other

All Journal Article (15 results) Book (1 results) Publications (27 results)

  • [Journal Article] Detection of plasma hnRNP B1 mRNA, a new cancer biomarker, in lung cancer patients by quantitative real-time Polymerase Chain Reaction2005

    • Author(s)
      Sueoka, E.
    • Journal Title

      Lung Cancer (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population2005

    • Author(s)
      Yamamoto, H.
    • Journal Title

      Carcinogenesis 26

      Pages: 411-416

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients2005

    • Author(s)
      Yuasa, Y.
    • Journal Title

      Carcinogenesis 26

      Pages: 193-200

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Long-term effects of radiation dose on inflammatory markers in atomic bomb survivors2005

    • Author(s)
      Hayashi, T
    • Journal Title

      Am.J.Med. 118

      Pages: 83-86

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A single nucleotide polymorphism in the MMP-9 promoter affects tumor progression and invasive phenotype of gastric cancer2005

    • Author(s)
      Matsumura, S.
    • Journal Title

      J.Cancer Res., Clin., Oncol. 131

      Pages: 19-25

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Perspectives on cancer immuno-epidemiology2004

    • Author(s)
      Nakachi, K.
    • Journal Title

      Cancer Sci. 95

      Pages: 921-929

    • NAID

      10014260327

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Radiation-induced apoptosis of stem/progenitor cells in human umbilical cord blood is associated with alterations in reactive oxygen and intracellular pH.2004

    • Author(s)
      Hayashi, T.
    • Journal Title

      Mutat.Res. 556

      Pages: 83-91

    • Related Report
      2004 Annual Research Report
  • [Journal Article] First case of aplastic anemia in a Japanese child with a homozygous missense mutation in the NBS1 gene (1171V) associated with genomic instability2004

    • Author(s)
      Shimada, H.
    • Journal Title

      Hum.Genet. 115

      Pages: 372-376

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Excess concordance of cancer incidence and lifestyles in married couples (Japan) : survival analysis of paired rate data2004

    • Author(s)
      Izumi, S.
    • Journal Title

      Cancer Causes and Control 15

      Pages: 551-558

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Prediction of prognosis of estrogen receptor-positive breast cancer with combination of selected estrogen-regulated genes2004

    • Author(s)
      Yoshida, N.
    • Journal Title

      Cancer Sci. 95

      Pages: 496-502

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Allelic length of a CA dinucleotide repeat in the egfr gene correlates with the frequency of amplifications of this sequence - First results of an inter-ethnic breast cancer study2004

    • Author(s)
      Buerger, H.
    • Journal Title

      J.Pathol. 203

      Pages: 545-550

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A single nucleotide polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer2004

    • Author(s)
      Matsumura, S.
    • Journal Title

      J.Cancer Res., Clin., Oncol. 130

      Pages: 259-265

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Improving the efficiency of nested case-control studies of interaction by selecting controls using counter matching on exposure2004

    • Author(s)
      Cologne, J.B.
    • Journal Title

      Int.J.Epidemiol. 33

      Pages: 485-492

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anisomycin downregulates gap junctional intercellular communication via the p38 MAP kinase pathway2004

    • Author(s)
      Ogawa, T.
    • Journal Title

      J.Cell Science 117

      Pages: 2087-2096

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Decreases in percentages of naive CD4 and CD8 T cells and increases in percentages of memory CD8 T-cell subsets in the peripheral blood lymphocyte populations of a-bomb survivors.2004

    • Author(s)
      Yamaoka, M.
    • Journal Title

      Radiat.Res. 161

      Pages: 290-298

    • Related Report
      2004 Annual Research Report
  • [Book] Immunology 2004 : Genomic Issues Immune System Activation and Allergy2004

    • Author(s)
      Hayashi, T.
    • Total Pages
      565
    • Publisher
      Medimond S.r.l.
    • Related Report
      2004 Annual Research Report
  • [Publications] Buerger, H: "Allelic length of a CA dinucleotide repeat in the egfr gene correlates with the frequency of amplifications of this sequence - First results of an interethnic breast cancer study."J.Pathol. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ogawa, T: "Anisomycin downregulates gap junctional intercellular communication via p38 MAP kinase pathway."J.Cell Science. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tanimoto, K: "Hypoxia-inducible factor-1a polymorphisms associated with enhanced transactivation capacity, implying clinical significance."Carcinogenesis. 24. 1779-1783 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuraoka, K: "A single nucleotide polymorphism in the transmembrane domain coding region of Her-2 is associated with development and malignant phenotype of gastric cancer."Int.J.Cancer. 107. 593-596 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hayashi, T: "HLA haplotype is associated with diabetes among atomic bomb survivors."Human Immunology. 64. 910-916 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tominaga, M: "Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin D1, and Ki-67."Lung Cancer. 40. 45-53 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 田島和雄監修, 中地 敬: "がん予防の最前線 (上)"昭和堂. 179 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tominaga, M.: "Detection and discrimination of preneoplastic and early stages of lung adenocarcinoma using hnRNP B1 combined with the cell cycle-related markers p16, cyclin D1, and Ki-67"Lung Cancer. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakachi, K.: "Can teatime increase one's lifetime?"Ageing Res.Reviews. 44. 1-10 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Members of Prospective Studies Collaboration: "Age-specific relevance of usual blood pressure to vascular mortality : a meta-analysis of individual data for one million adults in 61 prospective studies"Lancet. 360. 1903-1913 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fujiki, H.: "Involvement of TNF-α changes in human cancer development, prevention and palliative care"Mech.Ageing Develop.. 123. 1655-1663 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura, K.: "Comparative analysis of telomere lengths and erosion with age in human epidermis and lingual epithelium"J.Invest.Dermatol.. 119. 1014-1019 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuyama, S.: "Estrogen receptor β (ER-β) is expressed in human stomach adenocarcinoma"J.Cancer Res.Clin.Oncol.. 128. 319-324 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Xie, D.: "Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features"Cancer Res.. 61. 8917-8923 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suganuma, M.: "Helicobacter pylori membrane protein 1 : A new carcinogenic factor of Helicobacter pylori"Cancer Res.. 61. 63567-6359 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Park, S-C.: "Japan-Korea cancer research symposium : investigation on the balanced cooperation of cancer cells with the human body"J.Cancer Res.,Clin.,Oncol.. 127. 692-695 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Imai, K.: "Personality types, lifestyle, and sensitive to mental stress in association with NK activity"Int.J.Hygiene Environ.. 203. 1-7 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujiki, H.: "Cancer prevention with green tea and monitoring by a new biomarker hnRNP B1"Mutat.Res.. 481. 299-304 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suga, K.: "Molecular significance of excess body weight in postmenopausal breast cancer patients, in relation to expression insulin-like growth factor I receptor and insulin-like growth factor II gene"Jpn.J.Cancer Res.. 92. 127-134 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sueoka, N.: "Healthy Aging for Functional Logevity"New York Academy of Science. 385 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suga,K.,Nakachi,K.,Hayashi,S-I., et al.: "Molecular significance of excess body weight in postmenopausal breast cancer ptatients, in relation to expression of insulin-like growth factor I receptor and insulin-like growth factor II gene"Jpn.J.Cancer Res.. 92. 127-134 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakachi,K.,Miyake,S.,Suganuma,M., et al: "Preventive effects of drinking green tea on cancer and cardiovascular disease : Epidemiological evidence for multiple targeting prevention"BioFactors. 13. 49-54 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yoshida,T.,Nakachi,K.,Hayashi,S-I., et al: "Distinct mechanisms of loss of estrogen receptor α gene expression in human breast cancer : methylation of the gene and alteration of trans-acting factors"Carcinogenesis. 21. 2193-2201 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Imai,K.,Nakachi,K.,Miyake,S., et al: "Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence : an 11-year follow-up study of a general population"Lancet. 356. 1795-1799 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsuyama,S.,Nakachi,K.,Sueoka,E., et al: "Heterogeneous nuclear ribonucleoprotein B1 expressed in esophageal squamous cell carcinoma as a new biomarker for diagnosis"Jpn.J.Cancer Res.. 91. 658-663 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Eguchi,H.,Nakachi,K.,Hayashi,S-I et al: "Different expression patterns of Bcl-2 family genes in breast cancer by estrogen receptor status with special reference to pro-apoptotic Bak gene"Cell Death & Differ. 7. 439-446 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujiki,H.,Nakachi K.,Suganuma,M.,Sueoka,E., et al: "Dietary Anticarcinogenes and Antimutangens-Chemical and Biological Aspects"Royal society of chemistry, London. (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2018-03-28  

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