Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms and Colorectal Cancer: A Meta-Analysis of Epidemiologic Studies

Abstract

Studies investigating the association between vascular endothelial growth factor (VEGF) polymorphisms and colorectal cancer (CRC) risk report conflicting results. To clarify the effect of four VEGF (-460T/C, -634G/C, +936C/T, and -2578C/A) gene polymorphisms on the risk of developing CRC, we carried out a meta-analysis using published data to obtain more precise estimates of risk. Electronic searches of PubMed and EMBASE were conducted to select studies for this meta-analysis. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of CRC associated with four VEGF (-460T/C, -634G/C, +936C/T, and -2578C/A) gene polymorphisms. We identified 12 epidemiologic studies, which included 2770 CRC cases and 2568 controls. The combined results based on all studies showed that CRC cases had a significantly higher frequency of VEGF -634GG (OR=1.24, 95% CI=1.06, 1.44) and -2578AA (OR=1.37, 95% CI=1.12, 1.66) genotype and a lower frequency of -634CG (OR=0.82, 95% CI=0.71, 0.95) than controls. When stratifying for race, we found that patients with CRC had a significantly higher frequency of -460TC (OR=1.54, 95% CI=1.22, 1.94), -460CC (OR=2.00, 95% CI=1.50, 2.67), and -2578AA (OR=1.38, 95% CI=1.12, 1.69) and a lower frequency of -2578AA (OR=0.78, 95% CI=0.65, 0.93) genotypes of VEGF than controls, among Caucasians. We also found that patients with CRC had a significantly higher frequency of -634GG (OR=1.61, 95% CI=1.20, 2.15) and a lower frequency of -634CG (OR=0.60, 95% CI=0.46, 0.79) genotypes of VEGF than controls, among Asians. Our meta-analysis suggests that the VEGF -460T/C, -634G/C, and -2578C/A gene polymorphisms are associated with a risk of CRC.