Ozlem Timirci-Kahraman1, Nazli Ezgi Ozkan1, Saime Turan1, Ammad Ahmad Farooqi2, Levent Verim3, Tulin Ozturk4, Guldal Inal-Gultekin1, Turgay Isbir5, Oguz Ozturk1, Ilhan Yaylim1. 1. 1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey . 2. 2 Institute of Biomedical and Genetic Engineering (IBGE), KRL Hospital , Islamabad, Pakistan . 3. 3 Department of Urology, Haydarpasa Numune Training Hospital , Istanbul, Turkey . 4. 4 Department of Pathology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey . 5. 5 Department of Medical Biology, Faculty of Medicine, Yeditepe University , Istanbul, Turkey .
Abstract
AIM: The aim of this study was to evaluate the role of polymorphisms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR4) genes in bladder cancer susceptibility in a Turkish population. MATERIALS AND METHODS: The study group included 91 bladder cancer patients, while the control group comprised 139 individuals with no evidence of malignancy. Gene polymorphisms of TRAIL C1595T (rs1131580) and DR4 C626G (rs4871857) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The frequency of the TRAIL 1595 TT genotype was significantly lower in patients with bladder cancer compared to controls (p<0.001; odds ratios [OR]=0.143; 95% confidence interval [CI]=0.045-0.454). A significantly increased risk for developing bladder cancer was found for the group bearing a C allele for TRAIL C1595T polymorphism (p<0.001; OR=1.256; 95% CI=1.138-1.386). The observed genotype and allele frequencies of DR4 626 C/G in all groups were in agreement with the Hardy-Weinberg equilibrium (p=0.540). However, the frequency of DR4 GG genotype was found to be 2.1-fold increased in the bladder cancer patients with high-grade tumor, when compared to those having low-grade tumor (p=0.036). Additionally, combined genotype analysis showed that the frequency of TRAILCT-DR4GG was significantly higher in patients with bladder cancer in comparison with those of controls (p=0.037; OR=2.240; 95% CI=1.138-1.386). CONCLUSIONS: Our study provides new evidence that TRAIL 1595 C allele may be used as a low-penetrant risk factor for bladder cancer development in a Turkish population. Otherwise, gene-gene interaction analysis revealed that the DR4GG genotype may have a predominant effect on the increased risk of bladder cancer over the TRAIL CT genotype.
AIM: The aim of this study was to evaluate the role of polymorphisms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and death receptor (DR4) genes in bladder cancer susceptibility in a Turkish population. MATERIALS AND METHODS: The study group included 91 bladder cancerpatients, while the control group comprised 139 individuals with no evidence of malignancy. Gene polymorphisms of TRAILC1595T (rs1131580) and DR4C626G (rs4871857) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The frequency of the TRAIL 1595 TT genotype was significantly lower in patients with bladder cancer compared to controls (p<0.001; odds ratios [OR]=0.143; 95% confidence interval [CI]=0.045-0.454). A significantly increased risk for developing bladder cancer was found for the group bearing a C allele for TRAILC1595T polymorphism (p<0.001; OR=1.256; 95% CI=1.138-1.386). The observed genotype and allele frequencies of DR4626 C/G in all groups were in agreement with the Hardy-Weinberg equilibrium (p=0.540). However, the frequency of DR4 GG genotype was found to be 2.1-fold increased in the bladder cancerpatients with high-grade tumor, when compared to those having low-grade tumor (p=0.036). Additionally, combined genotype analysis showed that the frequency of TRAILCT-DR4GG was significantly higher in patients with bladder cancer in comparison with those of controls (p=0.037; OR=2.240; 95% CI=1.138-1.386). CONCLUSIONS: Our study provides new evidence that TRAIL 1595 C allele may be used as a low-penetrant risk factor for bladder cancer development in a Turkish population. Otherwise, gene-gene interaction analysis revealed that the DR4GG genotype may have a predominant effect on the increased risk of bladder cancer over the TRAIL CT genotype.
Authors: Nadezda Lipunova; Anke Wesselius; Kar K Cheng; Frederik J van Schooten; Jean-Baptiste Cazier; Richard T Bryan; Maurice P Zeegers Journal: Biomark Cancer Date: 2019-12-30