Zhong Weifeng, Wang Xiaohong, Pan Bin, Su Zexuan
Graduate School of Southern Medical University, 510515, Guangzhou, China,
Tumour Biol. 2014 Oct;35(10):9839-45. doi: 10.1007/s13277-014-2194-4. Epub 2014 Jul 3.
We investigated the association of three single nucleotide polymorphisms (SNPs) in VEGF gene with the prognosis of renal cell carcinoma (RCC) and its association with clinical characteristics of RCC, such as tumor stages, metastasis, and tumor size. Polymerase chain reaction (PCR) restriction fragment length polymorphism analysis was used to genotype specimens for three polymorphisms (-2578C/A, -1154G/A, and -634G/C) in the VEGF gene. Hazard ratios (HRs) and their confidence intervals (CIs) were used to analyze the association of three SNPs in the VEGF gene with survival time using a multivariate Cox proportional hazards model. Frequencies of VEGF-2578AA genotype and A allele were significantly higher in patients with III-IV tumor stage or larger tumor size when compared with CC genotype. Moreover, frequencies of VEGF-634CC genotype and C allele were significantly higher in patients with tumor size >4 cm when compared with -634GG genotype. By Cox proportional hazards model, patients carrying VEGF-2578AA genotype and A allele significantly increased the risk of death from RCC, with the adjusted HRs (95 % CI) of 2.23 (1.15-4.36) and 1.55 (1.11-2.17), respectively. Our study suggests that VEGF-2578C/A and VEGF-634G/C polymorphisms may have effects on the prognosis of RCC. This finding might help in clarifying the mechanisms of RCC development and progression.
我们研究了血管内皮生长因子(VEGF)基因中的三个单核苷酸多态性(SNP)与肾细胞癌(RCC)预后的关联,以及它们与RCC临床特征(如肿瘤分期、转移和肿瘤大小)的关联。采用聚合酶链反应(PCR)限制性片段长度多态性分析对VEGF基因中的三个多态性位点(-2578C/A、-1154G/A和-634G/C)进行标本基因分型。使用多变量Cox比例风险模型,采用风险比(HRs)及其置信区间(CIs)分析VEGF基因中的三个SNP与生存时间的关联。与CC基因型相比,III-IV期肿瘤或肿瘤较大的患者中VEGF-2578AA基因型和A等位基因的频率显著更高。此外,与-634GG基因型相比,肿瘤大小>4 cm的患者中VEGF-634CC基因型和C等位基因的频率显著更高。通过Cox比例风险模型,携带VEGF-2578AA基因型和A等位基因的患者死于RCC的风险显著增加,调整后的HRs(95%CI)分别为2.23(1.15-4.36)和1.55(1.11-2.17)。我们的研究表明,VEGF-2578C/A和VEGF-634G/C多态性可能对RCC的预后有影响。这一发现可能有助于阐明RCC发生和发展的机制。