2004 Fiscal Year Final Research Report Summary
Analysis of IGF-I related gene polymorphisms and their impact on prostate cancer in Japanese population
| Project/Area Number |
15591667
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | Akita University |
|---|
Principal Investigator |
HORIKAWA Yohei Akita University, School of Medicine, Lecturer, 医学部, 助手 (40361232)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HABUCHI Tomonori Akita University, School of Medicine, Professor, 医学部, 教授 (00293861)
TSUCHIYA Norihiko Akita University, School of Medicine, Associate Professor, 医学部, 助教授 (70282176)
TOGASHI Hisafumi Akita University, School of Medicine, Lecturer, 医学部, 助手 (30361231)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Prostate cancer / gene polymorphism / IGF-I / IGFBP3 / PSA |
|---|
| Research Abstract |
Insulin-like growth factor-I (IGF-I) plays an important role in prostate growth, hyperplasia, and carcinogenesis. We studied the association between IGF-I related gene polymorphism and Prostate cancer (PCa).
1.The circulating level of insulin-like growth factor-binding protein-3 (IGFBP-3) is inversely associated with the risk of PCa and its progression and may be modulated by the A/C polymorphism at position -202 in the promoter region of IGFBP-3. The polymorphism was analyzed by a PCR RFLP in 307 PCa patients and 227 male controls. No significant difference in the genotype frequency was found between the PCa and controls IGFBP3 gene. The-202 A/C polymorphism is correlated with Advanced disease status in PCa. The IGFBP-3 -202 A/C polymorphism was not associated with susceptibility to PCa in Japanese men, but the presence of the C allele may cumulatively increase the risk for tumor metastasis and for having tumors with a biologically more aggressive phenotype
2.PSA is an IGFBP-3 protease, which greatly lowers the affinity of IGFBP-3 to IGF-1 and decreases the serum IGFBP-3 levels in PCa patients. We examined the PSA polymorphisms at positions -158 and -252 in 300 PCa cases and 266 controls by the PCR-RFLP. However, the PSA polymorphisms may not be associated with the risk of PCa development and its disease progression, and may also be not related to the serum PSA level.
3.CA repeat polymorphism in the promoter region of the human IGF-I may be associated with circulating IGF-I level. The association of the polymorphism with the risk of PCa was explored in 303 patients with PCa and 262 controls. The 19-CA repeat allele was more frequently observed in the PCa compared with the controls. The 19 allele of IGF-I appears to increase the risk of PCa with a gene dosage effect in the Japanese population.
|
