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The identification of prostate cancer susceptible gene by whole genome search and candidate gene approach

Research Project

Project/Area Number 16591600
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKyushu University

Principal Investigator

YOKOMIZO Akira  Kyushu University, Urology, Research Associate, 大学病院, 助手 (60346781)

Co-Investigator(Kenkyū-buntansha) NAITO Seiji  Kyushu University, Urology, Professor, 大学院医学研究院, 教授 (40164107)
KOGA Hirofumi  Kyushu University, Urology, Associate Professor, 大学院医学研究院, 助教授 (20271108)
SASAZUKI Takehiko  International Medical Center of Japan, President, 総長 (50014121)
INOKO Hidetoshi  Tokai University, Molecular Life Science, Professor, 医学部・分子生命科学, 教授 (10101932)
YAMAMOTO Ken  Kyushu University, Molecular Genitics, Associate Professor, 生体防御医学研究所, 助教授 (60274528)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsprostate cancer / polymorphism / genome
Research Abstract

Introduction and Objective : The genetic polymorphisms may affect the of prostate cancer (Pca) susceptibility. HPC2/ELAC2 gene was identified by linkage analysis from familial cases in USA. While, HER-2 gene is a proto-oncogene, encoding a transmembrane tyrosine kinase receptor that has an important role in many human cancers including Pca. To determine the association of HPC/ELAC2 and HER2 gene with Japanese Pca, we analyzed the frequency of polymorphic sites of these two genes in sporadic Pca patients and matched controls.
Methods : We genotyped at Ser257Leu and Ala541Thr in HPC/ELAC2 gene, and at Ile655Val in HER-2 gene in sporadic Japanese Pca patients (n=285) and matched controls (n=233). Controls were unrelated Japanese men who had no history of cancer including Pca and normal PSA level (less than 4.0ng/m1). Statistical analyses were performed by Fisher's exact test and logistic regression analysis.
Results : We observed a significantly higher frequency of the Thr541 in HPC/ELAC2 gene in Pca patients (8.4%) compared to the control group (2.1%) (p=0.0030, Odds Ratio (OR) = 4.02). Also Va1655 in HER-2 gene was significantly lower frequency in Pca (14.7 % in cancer vs. 26.2 % in control, p=0.0025, OR=0.476).
Conclusions : Our results indicate that Thr541 in HPC/ELAC2 has a significance (OR =4.02) in the predisposition of sporadic Pca in Japan. The Thr 541 polymorphism was first reported to link to familial Pca in USA. In our analyses, similar phenomenon was observed in sporadic cases in Japan. While, the frequency of Va1655 in HER2 was significantly lower in Pca patients in Japan. This Va1655Val was previously reported that significant higher frequency was observed in breast cancer patients. This opposite observation between Pca and breast cancer may be affected by hormonal environment of these two cancers.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (18 results)

All 2007 2006 2005 2004

All Journal Article (18 results)

  • [Journal Article] The association analysis of Glutathion S-Transferase P1 Polymorphism with urothelial cancer susceptibility and myelosuppression after M-VAC chemotherapy.2007

    • Author(s)
      Yokomizo A
    • Journal Title

      Int.J.Urol. (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] The association analysis of Glutathion S-Transferase P1 Polymorphism with urothelial cancer susceptibility and myelosuppression after M-VAC chemotherapy.2007

    • Author(s)
      Yokomizo A, Yamamoto K, Kinukawa N, Tsunoda T, Koga H, Naito S.
    • Journal Title

      Int.J.Urol. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Percentage of positive biopsy cores, preoperative prostate-specific antigen (PSA) level, pT and Gleason score as predictors of PSA recurrence after radical prostatectomy : a multi-institutional outcome study in Japan.2006

    • Author(s)
      Yokomizo A
    • Journal Title

      BJU Int. 98

      Pages: 549-553

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Percentage of positive biopsy cores, preoperative prostate-specific antigen (PSA) level, pT and Gleason score as predictors of PSA recurrence after radical prostatectomy : a multi-institutional outcome study in Japan.2006

    • Author(s)
      Yokomizo A, Murai M, Baba S, Osamu Ogawa O, Tsukamoto T, Niwakawa M, Tobisu K, Kinukawa N, Naito S
    • Journal Title

      BJU Int. 98

      Pages: 549-553

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Inositol 1,4,5-trisphosphate (IP(3)) receptor type1 (IP(3)R1) modulates the acquisition of cisplatin resistance in bladder cancer cell lines.2005

    • Author(s)
      Tsunoda T, Koga H, Yokomizo A, Tatsugami K, Eto M, Inokuchi J, Hirata A, Masuda K, Okumura K, Naito S.
    • Journal Title

      Oncogene 24

      Pages: 1396-402

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of HER-2 Polymorphism with Japanese Sporadic Prostate Cancer Susceptibility.2005

    • Author(s)
      Yokomizo A, Koga H, Kinukawa N, Tsukamoto T, Hirao Y, Akaza H, Mori M, Naito S.
    • Journal Title

      Prostate 62

      Pages: 49-53

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Randomized Controlled Trial to Evaluate Radiation plus Endocrine Therapy or Endocrine Therapy alone for PSA failure after radical prostatectomy : Japan Clinical Oncology Group Study JCOG 0401.2005

    • Author(s)
      Yokomizo A, Tobisu K, Kawamoto H, Nihei K, Ishizuka N, Naito S.
    • Journal Title

      Jpn.J.Clin.Oncol. 35

      Pages: 34-36

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of HER-2 Polymorphism with Japanese Sporadic Prostate Cancer Susceptibility2005

    • Author(s)
      Yokomizo A
    • Journal Title

      Prostate 62

      Pages: 49-53

    • Related Report
      2005 Annual Research Report 2004 Annual Research Report
  • [Journal Article] Randomized Controlled Trial to Evaluate Radiation plus Endocrine Therapy or Endocrine Therapy alone for PSA failure after radical prostatectomy.2005

    • Author(s)
      Yokomizo A
    • Journal Title

      Jpn.J.Clin.Oncol 35

      Pages: 34-36

    • Related Report
      2005 Annual Research Report 2004 Annual Research Report
  • [Journal Article] Inositol 1,4,5-trisphosphate (IP(3)) receptor type1 (IP(3)R1) modulates the acquisition of cisplatin resistance in bladder cancer cell lines.2005

    • Author(s)
      Tsunoda T
    • Journal Title

      Oncogene 24

      Pages: 1396-1402

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 前立腺癌における疾病感受性遺伝子HER2とHPC2の多型解析2005

    • Author(s)
      横溝 晃
    • Journal Title

      日本腎泌尿器疾患予防医学研究会誌 12

      Pages: 13-15

    • NAID

      110003071632

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Alteration in copy numbers of genes as a mechanism for acquired drug resistance.2004

    • Author(s)
      Yasui K, Mihara S, Zhao C, Okamoto H, Saito-Ohara F, Tomida A, Funato T, Yokomizo A, Naito S, Imoto I, Tsuruo T, Inazawa J.
    • Journal Title

      Cancer Res. 64

      Pages: 1403-10

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] HPC2/ELAC2 Polymorphism Associated with Japanese Sporadic Prostate Cancer.2004

    • Author(s)
      Yokomizo A, Koga H, Kinukawa N, Tsukamoto T, Hirao Y, Akaza H, Mori M, Naito S.
    • Journal Title

      Prostate 61

      Pages: 248-252

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Anatomical features of periprostatic tissue and its surroundings : a histological analysis of 79 radical retropubic prostatectomy specimens.2004

    • Author(s)
      Kiyoshima K, Yokomizo A, Yoshida T, Tomita K, Yonemasu H, Nakamura M, Oda Y, Naito S, Hasegawa Y.
    • Journal Title

      Jpn.J.Clin.Oncol. 34

      Pages: 463-468

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gluthatione-S-transferase P1 polymorphism 1105V in familial and sporadic prostate cancer.2004

    • Author(s)
      Debes JD, Yokomizo A, McDonnell SK, Hebbring SJ, Christensen GB, Cunningham JM, Jacobsen SJ, Tindall DJ, Liu W, Schaid DJ, Thibodeau SN.
    • Journal Title

      Cancer Genet Cytogenet. 155

      Pages: 82-86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] HPC2/ELAC2 Polymorphism Associated with Japanese Sporadic Prostate Cancer2004

    • Author(s)
      Yokomizo A
    • Journal Title

      Prostate 61

      Pages: 248-252

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Gluthatione-S-transferase P1 polymorphism I105V in familial and sporadic prostate cancer2004

    • Author(s)
      Debes JD
    • Journal Title

      Cancer Genet Cytogenet. 155

      Pages: 82-86

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Alteration in copy numbers of genes as a mechanism for acquired drug resistance2004

    • Author(s)
      Yasui K
    • Journal Title

      Cancer Res. 64

      Pages: 1403-1410

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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