Functional polymorphisms in the vascular endothelial growth factor (VEGF) alter the susceptibility toward different gastrointestinal tract (GIT) cancers. In this study, we explored the association of VEGF-2578C/A and VEGF-460T/C polymorphisms with esophageal cancer (EC) risk. In total, 330 patients with EC and 330 controls for VEGF-2578C/A polymorphism and 316 patients with EC and 316 controls for VEGF-460T/C polymorphism were genotyped. AA genotype (p = 0.01) and A allele (p = 0.02) of VEGF-2578C/A and CC genotype (p = 0.04) and C allele (p = 0.04) of VEGF-460T/C polymorphism were significantly associated with an increased risk of EC. VEGF-2578C/A and VEGF-460T/C polymorphisms have been studied in different GIT cancers, but results are inconclusive. Therefore, we performed a meta-analysis to assess the association of these polymorphisms with the risk of GIT cancers. The PubMed, ScienceDirect, and Google Scholar databases were used to search the articles. Twenty-one studies on VEGF-2578C/A and 20 studies on VEGF-460T/C polymorphism were included in this meta-analysis. VEGF-2578C/A polymorphism was associated with the decreased risk of GIT cancer in the overall population under the overdominant model (p = 0.009). A significant association of VEGF-2578C/A polymorphism with GIT cancer risk has been observed in the middle easterners, Caucasians, and Asians under different genetic models. VEGF-460T/C polymorphism was significantly associated with an increased risk of GIT cancers in Caucasians. Stratification of the data on the basis of cancer type showed a significant association of VEGF-2578C/A polymorphism with the risk of gallbladder cancer, whereas VEGF-460T/C polymorphism was associated with the risk of hepatocellular cancer, gastric cancer, and colorectal cancer. Our meta-analysis suggested that VEGF-2578C/A and VEGF-460T/C polymorphisms were associated with GIT cancer risk.
Keywords: GIT cancer; VEGF; esophageal cancer; meta-analysis; polymorphism.