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乳癌の遺伝子診断法の確立

Research Project

Project/Area Number 08266264
Research Category

Grant-in-Aid for Scientific Research on Priority Areas (A)

Allocation TypeSingle-year Grants
Research InstitutionNippon Medical School

Principal Investigator

江見 充  日本医科大学, 老人病研究所, 教授 (90221118)

Co-Investigator(Kenkyū-buntansha) 霞 富士雄  癌研究会附属病院, 外科, 部長 (40085593)
飯田 有俊  日本医科大学, 老人病研究所, 助手 (10277585)
塚元 和弘  日本医科大学, 老人病研究所, 講師 (30253305)
Project Period (FY) 1996 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥35,500,000 (Direct Cost: ¥35,500,000)
Fiscal Year 1999: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1998: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1997: ¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1996: ¥8,000,000 (Direct Cost: ¥8,000,000)
Keywords乳癌 / 染色体欠失 / がん抑制遺伝子 / 予後因子 / 術後生存率 / 術後再発 / 予後遺伝子診断 / 再発率 / 生存率 / LOH / 遺伝子診断 / 癌抑制遺伝子 / 染色体欠失地図
Research Abstract

18ヶ所の染色体領域に存在する22ヶのDNA多形成マーカー座におけるLOHをマーカーとして、プロスペクティブ研究として術後5年以上経過した乳癌504症例についてLOHの有無と再発および生存率との関係を比較検討した。
(1.乳癌術後再発率との関連)乳癌手術患者(他病死、重複患者は除く)504例を対象に各染色体欠失(LOH)と術後再発との関連についてKaplan-Meier法、Log rank検定を用い検討した。乳癌504例中再発108例であり、平均観察期間は69.0か月(2-111か月)であった。再発率に関しては、3p25.1,8p21-22,13q12,17p13.3,22q13の各々の領域に欠失を認めた症例で、高頻度に術後再発の起こることが判明した。
(2.乳癌術後生存率との関連)対象504例中癌病死亡は63例であり、再発率と同様に検討した結果、1p34-35,13q12,17p13.3,17q21.1,3p25.1,8p21-22の6領域について各領域に欠失を認めた症例で癌死による術後生存率の低下を認めた。多変量解析ではt(腫瘍経),n(リンパ節転移) 同様1p34-35,3p25.1,17p13.3のLOHが独立した予後因子であった。各領域各々のRetentionに対するLOHの死亡に関する相対危険度は1.8-5.5倍であった。
(3.n0乳癌の予後因子としての検討)18領域のDNAマーカーを用い228例のn0乳癌症例の健存率との相関を検討した。その結果、1p36(D1S1612),1p34(D1S552)が予後に有意差を生じた。多変量解析において、1p34-36LOH p=0.0117(R.R.=5.8)で独立した予後因子であった。

Report

(4 results)
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Emi, M. et al.: "Correlation of Allelic Loss with Poor Postoperative survival in Breast Cancer"Breast Cancer. 6. 351-356 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yokota, T. et al.: "Localization of a Tumor Suppressor Gene Associated with Progression of Human Breast Cancer Within a 1-cM Interval of 8p22-p23.1"Cancer. 85. 447-452 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fukino, K. et al.: "Frequent Allelic Loss at the TOC Locus on 17p25.1 in Primary Breast Cancers"Genes, Chrom. Cancer. 24. 345-350 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Emi, M. , et al.: "Allelic loss at 1p34, 13q12, 17p13.3, and 17q21.1 Correlates with Poor Postoperative Prognosis in Breast Cancer"Genes, Chrom. Cancer. 26. 134-141 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Utada, Y. et al.: "Mapping of New Target Regions of Allelic Loss in Primary Breast Cancers to 1-cM intervals on Genomic contings at 6q21 and 6q25.3"Jpn. J. Cancer Res.. 91. 1-8 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Utada, Y. et al.: "Allelic Loss at 8p22 Region as Prognostic Cancer. Factor in Large and Estrogen Receptor Negative"Cancer. 88. 1410-1416 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 歌田貴仁 他: "からだの科学"日本評論社. 31-34 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 常泉道子 他: "外科治療"永井書店. 669-674 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ogaki,K. et al.: "Mapping of a New target Region of Allelic Loss to a 6-cM Interval at 21_q21 in Primary Breast Cancers." Genes., Chrom. Cancer.23. 244-247 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kurose,K. et al.: "Frequent Allelic Loss at 7p14-15 Associated with Aggressive Histologic Types of Breast Cancer." Jpn.J.Cancer Res.89. 533-538 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Minobe,K. et al.: "Allelic Loss on Chromosome 9qIs Associated with Lymph Node Metastasis of Primary Breast Cancer." Jpn.J.Cancer Res.89. 916-922 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iida,A. et al.: "Mapping of a new target region of allelic loss to a 2-cM interval at 22q13.1 in primary breast cancer." Genes., Chrom. Cancer.21. 108-112 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Emi,M. et al.: "Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers." Jpn.J.Cancer Res.89. 12-16 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yokota,T. et al.: "Localization of a Tumor Suppressor Gene Associated with Progression of Human Breast Cancer With in a 1-cM Interval of 8p22-p23.1" Cancer. 83. 447-452 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 美濃部かおり 他: "乳癌の臨床 13" 篠原出版, 541-546 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 板東功一 他: "日本乳癌検診学会誌" 日本乳癌検診学会編集, 247-256 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Emi,M.,Mastumoto,S.,et.al.: "Correlation of Allelic Losses and Clinicopathological Factors in Primary Breast Cancers." Breast Cancer. 4. 243-237 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Emi,M.,Mastushima,M.,et.al.: "Multiplex mutation screening of the BRCA1 gene in 1000 Japanese breast cancers." Jpn.J.Cancer Res.89. 12-16 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsukamoto,K.,Emi,M.,et.al.: "Allelic loss on chromosome lp is associated with progression and lymph node metastasis of primary breast carcinoma." Cancer. 82. 317-322 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iida,A.,Emi,M.,et.al.: "Mapping of a new target region of allelic loss to a 2-cM interval at 22q/3.1 in primary breast cancer." Genes,Chrom.Cancer. 21. 108-112 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Matsumoto,S.,Emi,M.,et al.: "Detailed deletion mapping of chromosome arm 3p in breast cancers." Genes,Chrom.Cancer. 20. 268-274 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yokota,T.,Emi,M.et al.: "Mapping of a breast cancer tumor suppressor gene locus to a 4-cM" Jpn.J.Cancer Res.88. 959-964 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsukamoto,K.: "Two distinct commonly deleted regions on chromosome 13q suggest involvement of BRCA2 and retinoblastoma gene in sporadic breast carinomas." Cancer. 78. 1929-1934 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Suzuki,H.: "Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancer." Genes,Chrom.Cancer. 17. 225-233 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Komiya,A.: "Allelic losses at loci on chromosome 10 are associated with metastasis and progression of human prostate cancer." Genes,Chrom.Cancer. 17. 245-253 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Iida,A.: "Localization of a breast cancer tumor-suppressor gene to a 3-cM interval within chromosomal region 16q22." Brit.J.Cancer. 75. 264-267 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakata,T.: "Identification of a new commonly deleted region within a 2-cM interval of 11p11 in breast cancer." Eur.J.Cancer. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Matsumoto,S.: "Detailed deletion mapping of chromosome 3p in breast cancer : a2-cM region on 3p14.3-21.1 and a5-cM region on 3p24.3-25.1 commonly deletod in tumors." Genes,Chrom.Cancer. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 江見充: "家族性乳癌" 篠原出版(土屋敦雄編集), 216 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 江見充: "遺伝子診療96" 医学書院(森 徹編集), 134 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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