The identification of prostate cancer susceptible gene by whole genome search and candidate gene approach
| Project/Area Number |
16591600
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kyushu University |
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Principal Investigator |
YOKOMIZO Akira Kyushu University, Urology, Research Associate, 大学病院, 助手 (60346781)
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| 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)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| 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)
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| Keywords | prostate cancer / polymorphism / genome |
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| 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.
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Report
(4 results)
Research Products
(18 results)
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[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
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Journal Title
BJU Int. 98
Pages: 549-553
Description
「研究成果報告書概要(欧文)」より
Related Report
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[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.
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Journal Title
Oncogene 24
Pages: 1396-402
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Cancer Res. 64
Pages: 1403-10
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Cancer Genet Cytogenet. 155
Pages: 82-86
Description
「研究成果報告書概要(欧文)」より
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