Departamento de Bioquímica III e Inmunología, Universidad de Granada, Spain.
Hum Immunol. 2013 Jan;74(1):98-103. doi: 10.1016/j.humimm.2012.10.014. Epub 2012 Oct 13.
Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in renal cell cancer (RCC). Published data on the association between polymorphisms of vascular endothelial growth factor (e.g., -2578C/A [rs699947], -460T/C [rs833061], +405C/G [rs2010963], and +936C/T [rs3025039]) and the risk of renal cell carcinoma are ambiguous and controversial. The aim of this investigation was to investigate this relationship in a series of Caucasian Spanish patients.
A case-control study was performed with 216 cases and 280 controls, genotyping subjects for VEGF polymorphisms using the predesigned TaqMan single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA, USA). The combined effect of the four gene polymorphisms on overall survival was studied by haplotype analysis.
The overall results suggest that polymorphisms or haplotypes in the VEGF gene do not modify the risk of RCC. We were unable to replicate the association of the -460T/C (rs833061) polymorphism with renal cancer risk. Data were also gathered on clinical-pathological results, tumor size, clinical stage, histological grade, and survival.
According to our analysis of their contribution to prognostic factors, VEGF polymorphisms do not appear to exert a significant influence on RCC progression or prognosis. This finding might be explained by the tumor biology and pathogenesis of clear cell RCC. Additional studies with larger sample sizes are needed in different ethnic groups to further assess this association.
血管内皮生长因子(VEGF)在促进血管生成中起着核心作用,并且在肾细胞癌(RCC)中过度表达。已发表的关于血管内皮生长因子(例如-2578C/A [rs699947],-460T/C [rs833061],+405C/G [rs2010963]和+936C/T [rs3025039])多态性与肾细胞癌风险之间关联的研究数据存在矛盾和争议。本研究旨在调查白种西班牙人群中的这种关系。
采用病例对照研究,共纳入 216 例病例和 280 例对照,使用预设计的 TaqMan 单核苷酸多态性(SNP)基因分型检测(Applied Biosystems,加利福尼亚州福斯特市)对 VEGF 多态性进行基因分型。通过单体型分析研究了四个基因多态性对总体生存率的综合影响。
总体结果表明,VEGF 基因的多态性或单体型不会改变 RCC 的风险。我们未能复制 -460T/C(rs833061)多态性与肾癌风险之间的关联。还收集了有关临床病理结果、肿瘤大小、临床分期、组织学分级和生存的数据。
根据我们对其对预后因素的贡献的分析,VEGF 多态性似乎不会对 RCC 的进展或预后产生重大影响。这一发现可能是由透明细胞 RCC 的肿瘤生物学和发病机制解释的。需要在不同种族群体中进行更大规模的研究来进一步评估这种关联。