Fukuda Hisami, Tsuchiya Norihiko, Narita Shintaro, Kumazawa Teruaki, Horikawa Yohei, Inoue Takamitsu, Saito Mitsuru, Yuasa Takeshi, Matsuura Shinobu, Satoh Shigeru, Ogawa Osamu, Habuchi Tomonori
Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Oncol Rep. 2007 Nov;18(5):1155-63.
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.
血管内皮生长因子(VEGF)是最有效的血管生成因子之一,被认为在肿瘤新生血管形成中起关键作用,且与前列腺癌的肿瘤进展和转移相关。本研究评估了VEGF T-460C多态性在前列腺癌风险和进展中的意义。在一项病例对照实验中,对270例前列腺癌患者和252名男性对照者进行调查,以评估VEGF T-460C多态性与前列腺癌风险的关联。分析了95例行根治性前列腺切除术患者的前列腺特异性抗原(PSA)复发情况以及99例诊断时已有转移患者的生存情况,以评估该多态性对癌症进展的影响。在多变量分析中,该多态性的CC和TC基因型与根治性前列腺切除术后PSA复发率显著高于TT基因型相关,并且是PSA复发的独立预测因素(P=0.011)。相比之下,TT基因型的转移性前列腺癌患者与CC和TC基因型相比,生存情况明显更差。在多变量分析中,TT基因型是癌症特异性生存的独立预测因素(P=0.006)。VEGF T-460C多态性可能对根治性前列腺切除术后的PSA复发以及晚期前列腺癌的生存都有重大影响。该多态性在前列腺癌不同状态下的分子机制应在进一步研究中阐明。