Open AccessHaplotype‐based association of Vascular Endothelial Growth Factor gene polymorphisms with urothelial bladder cancer risk in Tunisian population
Author(s) -
Ben Wafi Safa,
Kallel Amani,
Ben Fradj Mohamed Kacem,
Sallemi Ahmed,
Ben Rhouma Sami,
Ben Halima Meriam,
Sanhaji Haifa,
Nouira Yassine,
Jemaa Riadh,
Feki Moncef
Publication year - 2018
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.22610
Subject(s) - haplotype , genotype , bladder cancer , odds ratio , linkage disequilibrium , vascular endothelial growth factor , biology , allele , angiogenesis , population , medicine , oncology , genetics , immunology , cancer , vegf receptors , gene , cancer research , environmental health
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.