Association of Genetic Variants of VEGF gene with Gastric Carcinoma Risk

Abstract

To date, few association analyses with regard to gene variants and expression of vascular endothelial growth factor (VEGF) in gastric carcinoma (GC) have been reported. We hypothesized the variants might also affect susceptibility to GC. To evaluate the correlation of VEGF variants with risk and clinicopathological characteristics of this disease in China, we detected fourteen single nucleotide polymorphisms (SNPs) of VEGF gene in 311 patients with gastric carcinoma and 425 age and gender-matched controls by using Sequenom iplex. We investigated expression of VEGF in combination with cyclooxygenase-2 (COX-2) in 238 tissues samples of the cases by tissue microarray (TMA) and immunohistochemistry (IHC). There were no significant differences in genotype, allele and haplotype distributions of the 14 VEGF SNPs between the cases and the controls. However, we found that there were significant clinicopathological correlations of the rs3024994C/T with gender, the rs3025021C/T with tumor size, the rs3025039C/T with tobacco smoking, the rs3025030G/C with tumor location, tobacco smoking and alcohol drinking (P<0.05, respectively). A/A genotype (P=0.050, OR=0.39, 95%CI=0.15-1.00) and A allele (P=0.024, OR=0.64, 95%CI=0.43-0.94) of the rs833052 significantly reduced the VEGF expression and T allele of the rs3025007 increased the VEGF expression (P=0.017, OR=1.70, 95%CI=1.10-2.61) when compared to the C allele of both the variants, respectively. The VEGF expression displayed a significant association with COX-2 (rs= 0.178, P=0.006). We concluded that none of the 14 SNPs of VEGF gene was significantly associated with the susceptibility to GC. Both VEGF and COX-2 showed close correlations with invasion and progression in advanced GC.