Haplotype-based association of Vascular Endothelial Growth Factor gene polymorphisms with urothelial bladder cancer risk in Tunisian population.

Abstract

Accumulated data suggested that Vascular Endothelial Growth Factor is a major mediator in vasculogenesis, angiogenesis and recently in tumorigenesis. Therefore, we aimed to investigate for the first time the association between VEGF gene variants (-2549I/D (rs35569394), -2578C/A (rs699947), and +936C/T (rs3025039)) with urothelial bladder cancer (UBC) in Tunisian population. A total of 218 UBC patients and 204 controls were recruited and genotyped by Polymerase Chain Reaction technique. Odds ratios (OR) and 95% confidence intervals (CIs) were used to access the association between the VEGFA gene polymorphisms and UBC. We found a significant decreased risk association of -2578 C/A polymorphism with UBC (OR (95% CI), 0.62 (0.41-0.94), P=.026) for CA genotype and (OR (95% CI), 0.40 (0.21-0.76), P=.005) for double homozygous mutant genotype. No associations were found in case of both polymorphic sites of VEGF, vis. -2549I/D and +936C/T, respectively. Haplotype analysis revealed a strong linkage disequilibrium between -2578C/A and -2549I/D and CIC combination is the significant haplotype associated with increased risk of UBC (OR (95% CI), 3.63 (1.47-8.97), P=.005). Regarding tumor grade/stage and family history of cancer, no associations were found for -2578C/A polymorphism. CIC haplotype of VEGF gene may be important risk factor for UBC development in Tunisia.