title: Clinical implication of vascular endothelial growth factor T-460C polymorphism in the risk and progression of prostate cancer.
abstract: Vascular endothelial growth factor (VEGF), one of the most potent angiogenic factors, is suggested to play a crucial role in tumor neovascularization and is associated with tumor progression and metastasis in prostate cancer. This study evaluated the significance of the VEGF T-460C polymorphism in the risk and the progression of prostate cancer. In a case-control experiment, 270 patients with prostate cancer and 252 male controls were investigated to assess the association of the VEGF T-460C polymorphism with the risk of prostate cancer. Prostate-specific antigen (PSA) recurrence in 95 patients who underwent radical prostatectomy and survival in 99 patients with metastases at diagnosis were analyzed to evaluate the influence of the polymorphism in cancer progression. The CC and TC genotypes of the polymorphism were associated with significantly higher rates of PSA recurrence after radical prostatectomy than the TT genotype and were independent predictors of PSA recurrence (P=0.011) in a multivariate analysis. In contrast, metastatic prostate cancer patients with the TT genotype showed significantly worse survival as compared to the CC and TC genotypes. In a multivariate analysis, the TT genotype was an independent predictor of cancer-specific survival (P=0.006). The VEGF T-460C polymorphism may have a substantial impact on both PSA recurrence after radical prostatectomy and survival in advanced prostate cancer. The molecular mechanisms of the polymorphism on the differing status in prostate cancer should be elucidated in further studies.
authors.affiliation: Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
authors.forename: Hisami
authors.initials: H
authors.lastname: Fukuda
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tsuchiya
authors.forename: Shintaro
authors.initials: S
authors.lastname: Narita
authors.forename: Teruaki
authors.initials: T
authors.lastname: Kumazawa
authors.forename: Yohei
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Inoue
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Saito
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.forename: Shinobu
authors.initials: S
authors.lastname: Matsuura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Satoh
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.forename: Tomonori
authors.initials: T
authors.lastname: Habuchi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000556:secondary / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology; D011110:Polymorphism, Genetic; D011379:Prognosis; D011467:Prostate / Q000473:pathology; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000601:surgery; D012307:Risk Factors; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A