VEGF-A基因多态性对接受氟尿嘧啶为基础辅助化疗的结直肠癌患者预后的影响

目的: 本研究旨在探讨血管内皮细胞生长因子A（vascular endothelial growth factor A,VEGF-A）基因多态性位点对结直肠癌患者长期预后的影响。方法: 本研究为回顾性分析，纳入149例接受手术且术后接受氟尿嘧啶为基础辅助化疗的结直肠癌患者。术前收集患者外周血提取基因组DNA，用限制性片段长度多态性聚合酶链反应（PCR-RFLP）对多态性位点进行基因分型。149例患者的基因分型结果进行进一步验证并纳入最终分析。基因型和预后的单变量分析用Kaplan-Meier生存分析方法，并通过Cox风险比例模型对其他变量进行校正。结果: VEGF-A基因-94C>G位点在中国人群当中的突变频率为：GG型62例（41.6%），CG型61例（40.9%）和CC型26例（17.4%），最小等位基因频率为0.38，三种基因型的分布符合哈迪温伯格平衡（P=0.113）。三种基因型在基线临床资料中分布均衡，差异无统计学意义。对三种不同基因型患者构建的生存分析发现，CC型患者5年总生存期（OS）率显著较低，相对于GG/CG型患者来说具有显著的统计学差异（P=0.022）。经过多变量的Cox风险比例模型校正之后CC基因型相对于GG/CG型患者的较差的预后影响仍然存在，并且具有显著的统计学差异（OR=3.76，P=0.015）。结论: 在结直肠癌患者当中，VEGF-A基因-94C>G位点的突变纯合子CC基因型对结直肠癌患者的预后具有独立的影响意义。

Effects of polymorphism of vascular endothelial growth factor A on the prognosis of colorectal cancer patients received fluorouracil based adjuvant chemotherapy

AIM: To investigate the association between VEGF-A gene polymorphism and prognosis in patients with colorectal cancer. METHODS: This study was a retrospective analysis involved 149 patients with colorectal cancer who were underwent surgical treatment and received fluorouracil based adjuvant chemotherapy. Peripheral blood of the CRC patients was collected before surgery used to extract genomic DNA and the genotyping of -94C>G was carried out with PCR-RFLP. The genotype results of 149 patients were further verified and included in the final analysis. The correlation of -94C>G genotype and other variables was analyzed by logistic regression model. The univariate analysis of genotype and prognosis was carried out by Kaplan-Meier survival analysis, and multivariates were adjusted by Cox regression analysis.RESULTS:The prevalence of -94C>G in VEGF-A among the Chinese population are as follows: the GG genotype 62 cases (41.6%), CG genotype 61 cases (40.9%) and CC genotype 26 cases (17.4%), minimum allele frequency was 0.38. The distribution of three genotypes in accordance with Hardy-Weinberg Equilibrium (P=0.113). There were no statistical differences in the distribution of the three genotypes in baseline clinical data. The survival analysis of patients with different genotypes found that the 5 years OS rates of patients with CC genotype was significantly lower, which was statistically significant compared with those of GG/CG genotypes (P=0.022). Adjusted in multivariate Cox regression analysis, CC genotype was an independent factor for OS (OR=3.76, P=0.015). CONCLUSION: Among patients with colorectal cancer, the mutant homozygous CC genotype of VEGF-A -94C>G has independent influence on the prognosis of CRC patients.