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ヒト集団の長期追跡に基づく発がんと免疫の分子疫学研究

Research Project

Project/Area Number 18014028
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionRadiation Effects Research Foundation

Principal Investigator

中地 敬  Radiation Effects Research Foundation, 放射線生物学/分子疫学部, 部長 (00142117)

Co-Investigator(Kenkyū-buntansha) 楠 洋一郎  財団法人放射線影響研究所, 放射線生物学・分子疫学部, 副部長 (60333548)
林 奉権  財団法人放射線影響研究所, 放射線生物学・分子疫学部, 免疫学研究室長 (70333549)
濱崎 幹也  財団法人放射線影響研究所, 放射線生物学・分子疫学部, 副主任技師 (80443597)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 2007: ¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 2006: ¥5,900,000 (Direct Cost: ¥5,900,000)
Keywords免疫 / ハプロタイプ解析 / NKG2D / 炎症 / 原爆放射線 / 突然変異性 / 活性酸素
Research Abstract

埼玉コーホート研究と原爆被爆者免疫コーホート研究を統合して,免疫,炎症,放射線被曝,発がんの関係を明らかにするのが本研究の目標である。原爆被爆者コーホート研究では,平成18年度に測定系を確立した3つの生体マーカーを用いて,放射線感受性の個人差,放射線誘発遺伝的不安定性,血漿中の活性酸素代謝産物総量の測定を進めている。血漿活性酸素代謝産物については,平成19年度に440人について測定を完了し,1)持続性炎症の程度と強く相関し,2)過去の原爆放射線被曝線量と正の相関を示すことを予備的解析により見出した。
また,埼玉コーホート研究により,発がんに対する免疫的防御の指標であるNK活性の主たる遺伝的要因が,活性型受容体NKG2D遺伝子領域のハプロタイプであり,発がんリスクとも関係することを先に報告した(Cancer Res,2006)。現在,各種サイトカイン,T細胞免疫等の免疫学的データが得られている原爆被爆者コーホート研究参加者を対象に,末梢血NK細胞およびCD8陽性T細胞におけるNKG2Dの発現をフローサイトメトリーにより測定し,NKG2Dハプロタイプとの関連だけでなく,炎症免疫、T細胞免疫との関係を検討している。これまでに,900人の測定を完了した。予備的解析により,1).NKG2DハプロタイプはNK細胞のNKG2D受容体の発現と強く関連しており,2)この関連はCD8陽性細胞においても同様に観察された。この結果は,NKG2DハプロタイプがNK細胞の細胞障害性だけでなくT細胞免疫の遺伝的要因として関与している可能性を示す。さらに,第2次埼玉コーホート研究で詳細な免疫マーカーの測定を行った450人について,持続性炎症にNK細胞活性,保存血清を用いて新たに測定した各種血清サイトカイン.活性酸素代謝産物がどのように関与するのか現在検討を進めている。

Report

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

    (36 results)

All 2008 2007 2006 Other

All Journal Article (20 results) (of which Peer Reviewed: 15 results) Presentation (12 results) Remarks (4 results)

  • [Journal Article] Exon 19 0f EGFR mutation in relation to the CA-repeat polymorphism inintron 12008

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

      CancerSci.

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sixty Years of Follow-up of Hiroshima and Nagasaki Survivors:CurrentProgress in Molecular Epidemiology Studies2008

    • Author(s)
      Nakachi, K
    • Journal Title

      Mutat.Res.

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The association between RAD18 Arg302Gln polymorphism and the riskof human non-small-cell lung cancer2008

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

      J. Cancer Res. Clin. Oncol. 134

      Pages: 211-217

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-lasting alterations of the immune system by ionizing radiation exposure:Implications for disease development among atomic bomb survivors2008

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

      Int.J.Radiat.Biol. 84

      Pages: 1-14

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single nucleotide polymorphism in the RADl8 gene and risk of colorectalcancer in the Japanese population2007

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

      Oncol.Rep. 18

      Pages: 1171-1175

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Radiation sensitivity and genomic instability in the hematopoietic system:Frequencies of micronucleated reticulocytes in whole-body X-irradiatedBALB/c and C57BL/6 mice2007

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

      CancerSci. 98

      Pages: 1840-1844

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High-throughput spectrophotometric assay of reactive oxygen species in serum2007

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

      Mutat.Res. 631

      Pages: 55-61

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Demethylation of promoter C region of estrogen receptor α gene iscorrelated with its enhanced expression in estrogen-ablation resistant MCF-7cells2007

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

      J.SteroidBiochem.Mol.Biol. 105

      Pages: 106-114

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Short-term culture and yH2AX flow cytometry determine differences in individual radiosensirivity in human peripheral T lymphocytes2007

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

      Environ.Mol.Mutagen. 48

      Pages: 38-47

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation profile of EGFR gene detected by denaturing high-performanceliquid chromatography in Japanese lung cancer patients2007

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

      J.CancerRes.Clin.Oncol. 133

      Pages: 93-102

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of smoking and smoking cessation on lung cancer mortality in the Asia-Pacific region2007

    • Author(s)
      Members of Asia Pacific CohortStudies Collaboration
    • Journal Title

      Am.J.Epidemiol. 165

      Pages: 1280-1286

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blood cholesterol and vascular mortality by age, sex, and blood pressure: ameta-analysis of individual data from 61 prospective studies with 55000 vascular deaths2007

    • Author(s)
      Members of the Prospective Studies Collaboration
    • Journal Title

      Lancet 370

      Pages: 1829-1839

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypertension: its prevalence and population-attributable fraction for mortality from cardiovascular disease in the Asia-Pacific region2007

    • Author(s)
      Members of Asia Pacific Cohort Studies Collaboration
    • Journal Title

      J.Hypertens 25

      Pages: 73-79

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia Pacific region2007

    • Author(s)
      Members of Asia Pacific Cohort Studies Collaboration
    • Journal Title

      J.Hypertens 25

      Pages: 1205-1213

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose2007

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

      Mol.Carcinogenesis 46

      Pages: 242-248

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Short-term culture and γH2AX flow cytometry determine the difference of individual radiosensitivities in human peripheral T lymphocytes.2007

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

      Environ. Mol. Mutagen. 48

      Pages: 38-47

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mutation profile of EGFR gene detected by denaturing high-performance liquid chromatography in Japanese lung cancer patients.2007

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

      J. Cancer Res. Clin. Oncol. 133

      Pages: 93-102

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose.2007

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

      Mol. Carcinogenesis 46

      Pages: 242-248

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Japan-U.S. Cooperative Cancer Research Seminar on Molecular Epidemiological Characteristics of Lung and Colon Cancer Development among Atomic-bomb Survivors, Bethesda, U.S., 23-24 February 2006.2006

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

      Cancer Sci. 97

      Pages: 1279-1282

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Demethylation of promoter C region of estrogen receptor α gene is correlated with its enhanced expression in estrogen-ablation resistant MCF-7 cells.

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

      J. Steroid Biochem. Mol. Biol. (in press)

    • Related Report
      2006 Annual Research Report
  • [Presentation] 原爆被爆者末梢血リンパ球の in vitro 長期培養クローンにおける染色体不安定性について2007

    • Author(s)
      濱崎 幹也
    • Organizer
      第48回原子爆弾後障害研究会
    • Place of Presentation
      広島
    • Year and Date
      2007-06-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] Hiroshima 60 years: Monitoring of survivors-Current progress in molecular epidemioloegy studies2007

    • Author(s)
      Nakachi, K.
    • Organizer
      The 5th International Conference on Environmental Mutagens in Human Populations
    • Place of Presentation
      Antalya, Turkey
    • Related Report
      2007 Annual Research Report
  • [Presentation] 原爆被爆者集団における末梢血ナイーブCD4T細胞比率の加齢あるいは被ばく線量依存性の低下にCD45遺伝子多型との関連性は見られない2007

    • Author(s)
      楠 洋一郎
    • Organizer
      第17回日本サイトメトリー学会
    • Place of Presentation
      浦安
    • Related Report
      2007 Annual Research Report
  • [Presentation] 慢性C型肝炎ウイルス感染の肝病態の進行にともなうTh1優位の免疫応答2007

    • Author(s)
      楠 洋一郎
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] Effects of inflammation-related gene polymorphisms and atomic-bomb radiation exposure on gastric cancer risk2007

    • Author(s)
      Hayashi, T.
    • Organizer
      The 13th International Congress of Radiation Research
    • Place of Presentation
      San Francisco, California, USA.
    • Related Report
      2007 Annual Research Report
  • [Presentation] 血清・血液細胞における活性酸素種の分光光度法およびフローサイトメトリー法によるハイスループットな測定システム2007

    • Author(s)
      林 奉権
    • Organizer
      第8回.日韓がん老化シンポジウム
    • Place of Presentation
      岐阜
    • Related Report
      2007 Annual Research Report
  • [Presentation] Gastric cancer risks among atomic-bomb survivors differ by HLA class I genotype2007

    • Author(s)
      Hayashi, T.
    • Organizer
      The Joint ESTP/IFSTP Congress of Toxicologic Pathology
    • Place of Presentation
      Basel, Switzerland
    • Related Report
      2007 Annual Research Report
  • [Presentation] Effects of inflammation-related gene polymorphisms and atomic-bomb radiation exposure on gastric cancer risk2007

    • Author(s)
      Hayashi, T.
    • Organizer
      The 12th World Congress on Advances in Oncology and the 10th International Symposium on Molecular Medicine and Cancer Chemoprevention Symposium
    • Place of Presentation
      Crete, Greece
    • Related Report
      2007 Annual Research Report
  • [Presentation] 炎症関連サイトカイン遺伝子多型と原爆放射線被曝が胃がんリスクに及ぼす影響2007

    • Author(s)
      林 奉権
    • Organizer
      第37回日本免疫学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [Presentation] Cytogenetic instability in peripheral blood Tlymphocytes cultured in vitro from A-bomb survivors2007

    • Author(s)
      Hamasaki, K.
    • Organizer
      The 13th International Congress of Radiation Research
    • Place of Presentation
      San Francisco, California, USA.
    • Related Report
      2007 Annual Research Report
  • [Presentation] 試験管内でクローン増殖させた原爆被爆者Tリンパ球は染色体調査において遺伝的不安定性を示さない2007

    • Author(s)
      濱崎 幹也
    • Organizer
      第8回国際染色体異常シンポジウム
    • Place of Presentation
      淡路
    • Related Report
      2007 Annual Research Report
  • [Presentation] X線を全身照射したBALB/cおよびC57BL/6マウスにおける小核網状赤血球のフローサイトメトリーによる解析: 遺伝的不安定性が照射後長期にわたって生体内で持続する証拠2007

    • Author(s)
      濱崎 幹也
    • Organizer
      第50回日本放射線影響学会
    • Place of Presentation
      千葉
    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.rerf.jp/library/rr_e/rr0708.htm

    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.rerf.jp/library/rr/rr0617.htm

    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.rerf.jp/library/rr_e/rr0611.htm

    • Related Report
      2007 Annual Research Report
  • [Remarks]

    • URL

      http://www.rerf.jp/library/rr/rr0603.htm

    • Related Report
      2007 Annual Research Report

URL: 

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

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