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The Clarification of Aberrant DNA Methylation at CpG sites in Age-related Urogenital Cancers

Research Project

Project/Area Number 12470327
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYOTO UNIVERSITY (2001)
Akita University (2000)

Principal Investigator

HABUCHI Tomonori  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (00293861)

Co-Investigator(Kenkyū-buntansha) KOIZUMI Akio  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (50124574)
KATO Teteuro  Akita University, School of Medicine, Professor, 医学部, 教授 (40004642)
OGAWA Osamu  Kyoto University, Graduate School of Medicine,Professor, 医学研究科, 教授 (90260611)
KAMOTO Toshiyuki  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (00281098)
SATO Kazunari  Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (90270842)
柿沼 秀秋  秋田大学, 医学部, 助手 (70323144)
三品 睦輝  秋田大学, 医学部, 助手 (30301063)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2001: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥10,400,000 (Direct Cost: ¥10,400,000)
KeywordsUrothelial Cancer / Prostate Cancer / Bladder Cancer / DNA Methylation / DBCCR1 / DNA Polymorphism / Chromosome 9 / メテレーション / 加齢 / 遺伝子 / 分子遺伝学 / 分子生物学
Research Abstract

In this era of present high-age generations, the incidence of urogenital cancers, especially those of the bladder and the prostate has been rising. On the other hand, recent molecular studies have shown that aberrant DNA methylation at CpG sites are widely involved in the development and progression of human cancers. Furthermore, age-related aberrant DNA methylation has been also reported in normal tissues, suggesting that the DNA methylation may be an earliest step in human carcinogenesis. The purpose of this study project was to clarify the role of aberrant DNA methylation in age-related urogenital cancers, and further to develop preventive strategies for such cancers.
We first analyzed that the DNA methylation pattern of the CpG island-promoter region of the DBCCR1 gene located at the 9q32-33 bladder cancer tumor suppressor locus. The results indicated that the aberrant DNA methylation at the locus is one of an earliest event in bladder carcinogenesis, suggesting the presence of methylation-based field defect of aged normal urothelium.
To further delineate the role ot DNA polymorphisms in age-related carcinogenesis, we have been performing the case-control study using the single-nucleotide polymorphisms of cancer related genes in baldder cancer and the those of steroid-hormone related genes in prostate-cancer.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (36 results)

All Other

All Publications (36 results)

  • [Publications] Wang L: "Cyclin D1 gene polymorphism is associated with an increased risk of urinary bladder cancer"Carcinogenesis. 23. 257-264 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang L: "No association between HER-2 gene polymorphism at codon 655 and a risk of bladder cancer"Int. J. Cancer. 97. 787-790 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsuchiya N: "Quantitative analysis of gene expressions of vascular endothelial growth factor-related factors and their receptors in renal cell carcinoma"Tohoku J. Exp. Med.. 195. 101-113 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujiwara H: "Definition of a 1-Mb homozygous deletion at 9q32-33 in a human bladder-cancer cell line"J. Hum. Genet.. 46. 372-377 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kakinuma H: "BCL10 is not a major target for frequent loss of 1p in testicular germ cell tumors"Cancer Genet. Cytogenet.. 126. 134-138 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Habuchi T: "Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer"Oncogene. 20. 531-537

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahasi T: "Distinct microsatellite alterations in upper urinary tract tumors and subsequent bladder tumors"J. Urol.. 165. 672-677 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Habuchi T: "Increased risk of prostate cancer and benign prostatic gyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect"Cancer Res.. 60. 5710-5713 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Higashi S: "Allelic imbalances on chromosome 20 in human transitional cell carcinoma"Jpn. J. Cancer Res.. 91. 499-503 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wu X-X: "Telomerase activity in urine after transurethral resection of superficial bladder cancer and early recurrence"Int. J. Urol. 7. 210-217 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi T: "Molecular diagnosis of metastatic origin in a patient with metachronous multiple cancers of the renal pelvis and the bladder"Urology. 56. 331-333 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Habuchi T: "Association of vitamin D receptor gene oplymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population"Cancer Res.. 60. 305-308 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang L, Habuchi T, Takahashi T, Mitsumori K, Kamoto T, Kakehi Y, Kakinuma H, Sato K, Nakamura A, Ogawa 0, and KatoT.: "Cyclin D1 gene polymorphism is associated with an increased risk of urinary bladder cancer"Carcinogenesis. 23. 257-264 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wang L, Habuchi T, Takahashi T, Kamoto T, Zuo T, Mitsumori K, Tsuchiya N, Sato K, Ogawa 0, Kato T: "No association between HER-2 gene polymorphism at codon 655 and a risk of bladder cancer"Int J Cancer. 97. 787-790 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsuchiya N, Sato K, Akao T, Kakinuma H, Sasaki R^ Shimoda N, Satoh S, Habuchi T; Ogawa O, KatoT: "Quantitative analysis of gene ecpressions of vascular endothelial growth factor-related factors and receptors in renal cell carcinoma"Tohoku J Exp Med. 195. 101-113 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujiwara H, Emi M, Nagai H Ohgaki K, Imoto I, Akimoto N,Ogawa O, and HabuchiT: "Definition of a 1-Mb homozygous deletion at 9q32-33 in a human bladder-cancer cell line"J Hum Genet. 46. 372-377 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kakinuma H, Habuchi T, Ito T, Mishina M, Sato K, Satoh S, AkaoT, Ogawa 0, Kato T: "BCL10 is not a major target for frequent loss of 1p in testicular germ cell tumors"Cancer Genet Cytogenet. 126. 134-138 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Habuchi T, Takahashi T, Kakinuma H, Wang L, Tsuchiya N,Satoh S, Akao T, Sato K, Ogawa 0, Knowles MA, Katp T: "Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer"Oncoaene. 20. 531-537 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi T, Kakehi Y, Mitsumori K, Akao T, Terachi T, Kato T,Ogawa 0, and Habuchi T: "Distinct microsatellite alterations in upper urinary tract tumors and subsequent bladder tumors"J. Urol. 165. 672-677 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Habuchi T, Liqing Z, Suzuki T, Sasaki R, Tsuchiya N, Tachiki H,Shimoda N, Satoh S, Sato K, Kakehi Y, Kamoto T, Ogawa 0, and Kato T: "Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect"Cancer Res. 60. 5710-5713 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Higashi S, Habuchi T, Takahashi T, Kamoto T, Kakehi Y,Ogawa O, and Hiai H: "Allelic imbalances on chromosome 20 in human transitional cell carcinoma"Jpn. J. Cancer Res. 91. 499-503 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Wu X.-X.,Kakehi Y, Takahashi T, Habuchi T; and Ogawa O: "Telomerase activity in urine after transurethral resection of superficial bladder cancer and early recurrence"Int. J. Urol. 7. 210-217 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi T, Habuchi T, Kakehi Y, Okuno H, Terachi T, Katb T,and Ogawa 0: "Molecular diagnosis of metastatic origin in a patient with metachronous multiple cancers of the renal pelvis and the bladder"Urology. 56. 331-333 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Habuchi T, Suzuki T, Sasaki R, Wang L, Sato K, Satoh S, Akao T, Tsuchiya N, Shimoda N, Yasuhiko Wada Y, Koizumi A, Chihara J, Ogawa O, and KatoT: "Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population"Cancer Res. 60. 305-308 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Lizhong Wang: "Cyclin D1 gene polymorphism is associated with an increased risk of urinary bladder cancer"Carcinogenesis. 23・2. 257-264 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Lizhong Wang: "No association between HER-2 gene polymorphism at codon 655 and a risk of bladder cancer"International Journal of Cancer. 97・6. 787-790 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomonori Habuchi: "Hypermethylation at 9q32-33 tumour suppressor region is age-related in normal urothelium and an early and frequent alteration in bladder cancer"Oncogene. 20・4. 537-537 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomonori Habuchi: "Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect"Cancer Research. 60・20. 5710-5713 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takeshi Takahashi: "Distinct microsatellite alterations in upper urinary tract tumors and subsequent bladder tumors"Journal of Urology. 165・2. 672-677 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujiwara H: "Definition of a 1-Mb homozygous deletion at 9q32-33 in a human bladder-cancer cell line"Journal of Human Genetics. 46・7. 372-377 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tomonori Habuchi, et al.: "Hypermethylation at 9q32-33 Tumour Suppressor Region is Age-Related in Normal Urothelium and an Early and Frequent Alteration in Bladder Cancer"Oncogene. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeshi Takahashi, et al.: "Distinct microsatellite alterations between upper urinary tract tumors and subsequent bladder tumors."Journal of Urology. (印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomonori Habuchi, et al.: "Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect."Cancer Research. 60・20. 5710-5713 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomonori Habuchi, et al.: "Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostatic hyperplasia in a Japanese population."Cancer Research. 60・2. 305-308 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takeshi Takahashi, et al.: "Molecular diagnosis of metastatic origin in a patient with metachronous multiple cancers of the renal pelvis and the bladder."Urology. 56・2. 331-331 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shin Higashi et al.: "Allelic imbalances on chromosome 20 in human transitional cell carcinoma. "Japanese Journal of Cancer Research. 91・5. 499-503 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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