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

摘要

Background/Aim 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. Methods 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 ( CI s) were used to access the association between the VEGFA gene polymorphisms and UBC . Results 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. Conclusion CIC haplotype of VEGF gene may be important risk factor for UBC development in Tunisia.