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

摘要

Background: 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. Methods: 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. Results: 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. Conclusions: Our meta-analysis suggests that the VEGF -460T/C, -634G/C, and -2578C/A gene polymorphisms are associated with a risk of CRC.