title: Association of death receptor 4, Caspase 3 and 5 gene polymorphism with increased risk to bladder cancer in North Indians.
abstract: OBJECTIVE
  Perturbed apoptosis due to missense alterations in candidate tumor suppressor gene Death receptor 4 (DR4) and in caspases (Casp) lead to deregulated cell proliferation and cancer predisposition. Some data indicate that normal variations within the sequence of apoptotic genes may lead to suboptimal apoptotic capacity and therefore increased cancer risk. To test our proposal we examined whether six single nucleotide polymorphisms (SNPs) of the DR4 and Casp3, 5 genes contrive the risk of bladder cancer (BC) in a North Indian population.
  
  
  METHODS
  Genotyping was performed in 200 BC patients and 225 controls by Allele-specific PCR and by polymerase chain reaction-restriction fragment length polymorphism.
  
  
  RESULTS
  In DR4 Arg141His, BC patients having AA genotype (p = 0.036; OR = 2.51. In Casp5Leu13Phe G > C, significant association was observed with GC (p = 0.025; OR = 1.78) and also in GC + CC (p = 0.026; OR = 1.68). C allele carriers in Casp5Ala90Thr T > C showed low risk of BC (p = 0.036; OR = 0.83). While in Casp3 G > A, AG (p = 0.003; OR = 2.11), GG (p = 0.050; OR = 2.18), G allele (p < 0.001; OR = 1.85) and its carrier AG + GG (p = 0.001; OR = 2.12) have shown significant BC risk. Significant association between DR4 Ala228Glu polymorphism and smoking was observed in BC risk. Haplotype analysis demonstrated that DR4 (Thr209Arg-Arg141His-Ala228Glu) C-G-C is associated with 1.8 folds (OR = 1.85; p = 0.033) risk. GG genotype of Casp3 G > A polymorphism showed increased risk of recurrence (p = 0.009; HR = 5.20).
  
  
  CONCLUSIONS
  This study provided new support for the association of DR4 and Casp3, 5 in BC development, the tumorigenic effect of which was observed to be more enhanced in case of smoking exposure.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. ramamittal@gmail.com
authors.forename: R D
authors.initials: RD
authors.lastname: Mittal
authors.forename: P
authors.initials: P
authors.lastname: Srivastava
authors.forename: T
authors.initials: T
authors.lastname: Mittal
authors.forename: A
authors.initials: A
authors.lastname: Verma
authors.forename: P K
authors.initials: PK
authors.lastname: Jaiswal
authors.forename: V
authors.initials: V
authors.lastname: Singh
authors.forename: R K
authors.initials: RK
authors.lastname: Mandal
authors.forename: A
authors.initials: A
authors.lastname: Mandhani
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D053148:Caspase 3 / Q000235:genetics*; D020169:Caspases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*; D012907:Smoking / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C099217:CASP5 protein, human; D053148:Caspase 3; D020169:Caspases