title: Genetic variants in the tumor necrosis factor-related apoptosis-inducing ligand and death receptor genes contribute to susceptibility to bladder cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey .
authors.forename: Ozlem
authors.initials: O
authors.lastname: Timirci-Kahraman
authors.affiliation: 1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey .
authors.forename: Nazli Ezgi
authors.initials: NE
authors.lastname: Ozkan
authors.affiliation: 1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey .
authors.forename: Saime
authors.initials: S
authors.lastname: Turan
authors.affiliation: 2 Institute of Biomedical and Genetic Engineering (IBGE), KRL Hospital , Islamabad, Pakistan .
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
authors.affiliation: 3 Department of Urology, Haydarpasa Numune Training Hospital , Istanbul, Turkey .
authors.forename: Levent
authors.initials: L
authors.lastname: Verim
authors.affiliation: 4 Department of Pathology, Cerrahpasa Medical Faculty, Istanbul University , Istanbul, Turkey .
authors.forename: Tulin
authors.initials: T
authors.lastname: Ozturk
authors.affiliation: 1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey .
authors.forename: Guldal
authors.initials: G
authors.lastname: Inal-Gultekin
authors.affiliation: 5 Department of Medical Biology, Faculty of Medicine, Yeditepe University , Istanbul, Turkey .
authors.forename: Turgay
authors.initials: T
authors.lastname: Isbir
authors.affiliation: 1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey .
authors.forename: Oguz
authors.initials: O
authors.lastname: Ozturk
authors.affiliation: 1 Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey .
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
mesh_terms: D017209:Apoptosis / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000097:blood / Q000235:genetics*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human