VEGF基因多态性与非小细胞肺癌发病风险的相关性研究

Polymorphisms of VEGF gene and risk of lung cancer

目的血管内皮生长因子（vascular endothelial growth factor,VEGF）与肿瘤血管生成、生长和转移密切相关,该基因的多态位点可能影响基因的表达从而影响肿瘤的发生和发展,本研究采用病例-对照的方法,探讨VEGF基因多态性与肺癌发病风险的关系。方法采用聚合酶链反应-限制性片段长度多态性技术检测300例肺癌患者和300例对照人群VEGF基因-2578C/A多态性位点基因型和等位基因频率分布情况。结果 VEGF-2578C/A位点,C/C、C/A、A/A三个基因型在肺癌组和对照组中的分布频率分别为58.3%、34.7%、7.0%和69.7%、25.0%、5.3%,两组相比差异有显著性（χ2=8.384,P=0.015）,肺癌组中A等位基因型的频率为25.3%显著高于对照组17.8%（P=0.006）,与C/C基因型相比,携带A（C/A＋A/A）等位基因型能明显增加肺癌的发病风险（OR=1.644,95%CI=1.168-2.314）;以吸烟状况分层分析,携带A等位基因型能明显增加吸烟人群中肺癌的发病风险（OR=2.017,95%CI=1.218-3.342）;以病理类型分层分析发现,C/C、C/A、A/A基因型在鳞癌患者组中的频率为50.5%、40.7%和8.8%,与对照组相比差异有显著性（P=0.006）,携带A等位基因型能明显增加鳞癌的发病风险（OR=2.172,95%CI=1.344-3.508）。结论本研究结果提示VEGF-2578A等位基因型能明显增加肺癌的发病风险,并且与肺癌的病理类型有关。

[ Objective ] Angiogenesis is an essential process in the development, growth, and metastasis of malig- nant tumors. Polymorphisms in the vascular endothelial growth faetor（VEGF） gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. This study was designed to investigate the correlation of -2578C/A SNPs with the risk of Lung Cancer. [ Methods ] Genotypes were analyzed by polymerase chain reaction restriction fragment length polymorphism （PCR-RFLP） assay method in 377 patients with lung cancer and 416 matched healthy controls. [Results] The 2578C/A SNP, C/C C/A A/A genotpye frequencies in patients and controls group were 58.3%,34.7%, 7.0%and 69.7%,25.0%,5.3% respectively. There was a significant difference between the two group （X2=8.384, P = 0.015）. The frequency of allele A（25.3%） was significantly higher than the healthy controls 17.8% （P =0.006）. Compared with the C/C genotype, the allele A（C/A＋A/A） could significantly increase the risk of lung cancer, （OR=1.644, 95%CI=1.168-2.314）. Stratified analysis on smoking condition and A type alleles caMerscan significantly increase the risk of lung cancer in smokers （OR=2.017, 95%CI=l.218-3.342）.Stratification analysis showed that the C/C C/A A/A genotpye frequencies in squamouscell carcinoma were 50.5%,40.7%,8.8%with significant differencecompared with the control groups. A significant increase in lung cancer risk was seen among squamouscell carcinoma groups if they carried at least one A allele （OR=2.172, 95%CI=1.344-3.508） compared to control individuals without carrying these genotype. [ Conclusion] Our results indicated that VEGF-2578A allele could significantly increase the risk of lung cancer, played different roles in different pathological type.