| Project/Area Number |
12557133
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Urology
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
HATANO Tadashi (2001-2002) University of the Ryukyus, Faculty of Medicine, Dept. of Urology, Associate Professor, 医学部・泌尿器科, 助教授 (10101924)
内藤 絢子 (2000) 琉球大学, 医学部・附属病院, 助手 (40239356)
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| Co-Investigator(Kenkyū-buntansha) |
TACHIBANA Masaaki Tokyo Medical College, Dept. of Urology, Professor, 泌尿器科, 教授 (70129526)
NAITO Ayako University of the Ryukyus, Faculty of Medicine, Dept. of Urology, Lecturer, 医学部・泌尿器科, 助手 (40239356)
OGAWA Yoshihide University of the Ryukyus, Faculty of Medicine, Dept. of Urology, Professor, 医学部・泌尿器科, 教授 (50051719)
MIYAKAWA Michiko Hosei University, Faculty of Humanity and Environment, Associate Professor, 人間環境学部, 助教授 (30276216)
秦野 直 琉球大学, 医学部, 助教授 (10101924)
堀口 裕 慶應義塾大学, 医学部, 助手 (60229234)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | vitamin D receptor gene / urological disease / PCR-RFLP / single nucleotide polymorphism / SNP / microsatellite analysis / high risk group / 泌尿器科疾患 / 前立腺癌 / hight risk group |
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| Research Abstract |
Firstly, single nucleotide polymorphisms (SNPs) of vitamin D receptor gene were examined using three PCR-RFLP markers spanning between intron 8 and exon 8 in the healthy volunteers and the patients with urological problems including prostate cancer, other cancers and urolithiasis. Three restriction sites were ApaI, BamHI and TaqI. Genotypes in 101 of control samples were, TT (74.3%), Tt (24.8%) and tt (1.0%) for TaqI, BB (4.0%), Bb (27.7%) and bb (68.3%) for BamHI, AA (11.9%), Aa (43.6%), and aa (44.6%) for ApaI. In the patient with urolithiasis, t allele was indicated as a risk factor for the recurrent disease. Secondly, deletion mapping of chromosome 6 in 40 cases of renal cell carcinoma was performed. Six microsatellite markers on 6q, 22.3 cM from D6S975 to D6S1577 were analyzed. 13 cases out of 40 (33%) were found to have LOH at least one out of 5 markers. Among the cases with LOH, LOH in the 17.1 cM region with D6S311 and/or the 9.8 cM region with D6S441 were frequently observed. No remarkable findings were seen in prostate cancer cases in the same analysis. Thirdly, mutation analysis of BRG1 gene using PCR-SSCP was performed. BRG1 gene is located at 19p where deletion is frequently seen in prostate cancer. Variation of the genotype of BRG1 gene was observed in exon 9. Direct sequencing revealed SNP33978 of T/T, T/C, C/C. The patients with T/T genotype of SNP33978 were diagnosed at significantly younger ages (p=0.03). Young patients (age<62 years) with T/T genotype were more frequently to have high grade, advanced stage and metastatic tumors than patients with the T/C or C/C genotype (p=0.0134). It was suggested to be useful in preventive medicine, in decision making of therapeutic options and in predicting prognosis patients with cancer to analyze the variation and the combination of several germline SNPs.
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