Analyses of the genetic polymorphism of metabolic enzymes and identification of the high risk grourp for prostate cancer.
| Project/Area Number |
09671623
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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 | Mie University |
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Principal Investigator |
FUKUTOME Kazuo (1998) Mie University, Hospital, assistant, 医学部附属病院, 助手 (40270681)
渡辺 昌俊 (1997) 三重大学, 医学部, 助教授 (90273383)
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| Co-Investigator(Kenkyū-buntansha) |
YATANI Ryuichi , 学長 (80024636)
YAMAKAWA Kensuke Mie University, Faculty of Medicine, assistant, 医学部, 助手 (00230326)
福留 寿生 三重大学, 医学部, 助手 (40270681)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | metabolic enzyme / genetic polymorphism / prostate cancer / risk assessment |
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| Research Abstract |
Recently a considerable number of studies have been made on the association between the genetic polymorphisms of xenobiotic-metabolizingenzynes and cancer susceptibility. In this study, we analyzed the potential involvement of these genetic PO morphisms in prostate cancer (PCa).Genornic DNA was isolated fran peripheral blood arid genotyping was performed by allele-specificPCR.Cytochrcxne 2450 lAI (CYP lAl) catalyzes rrost carcinogenic polycyclic arcrnatic hydrocarbons.The CYPAl Val/Val genotype significantly increased the risk for PCa (QR=2.6 ; 95% CI=l .11-6.25).Glutathion S-transferase Ml (GSTM1) , a family of phase II enzynes, conjugates rretabolic interrrediates to water soluble forms and it is involved in detoxification of carcinogens. Individuals with the GS2N1 null genotype derronstratei a slightly increased risk (OR=l .3 ; 95% CI=0.82-2.04). The combination of the CYP1AI Val allele and GMSTM1 null genotype was associated with a higher risk (OR=2 .3 ; 95% CI=l.18-4 .48). The frequency of the GST Ml null genotype was alsohigher in patients with advanced St age disease. N-acetyLtransferase 1 (NAT1) catalyzes o-acetylation of PhIP, one of the carcinogenic heterocycic aminesr which was reported to induceprostate cancer in rats. The NAT1 *10 horrozygotes had a significantly higher risk for PCa (OR=2.4 ; 95% CI=l .0-5.6). CYP2E1 and GSTT2 were also analyzed and CYP2E1 cl allele and G5TT positive showed slightly increased risk (OR=l.3 ; 95%CI=0.36-4.53, OR=l.5 ; 95%CI=0.98-2.45, respectively). Furthermore, we found that the risk was elevated with increasing number of high risk genotypes. Individuals with more than four risk genotypes had 4.9 tines higher risk than with 0 or 1 riskgenotype (95% CI=l .39-17.31) . These results might indicate that analyses of genetic polyrrorphisms were helpful in identifying the high risk group.
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Report
(3 results)
Research Products
(23 results)
