title: Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4, and -9 in a case-control study with bladder cancer susceptibility in a North Indian population.
abstract: OBJECTIVE
  Impairment of the immune system may contribute to the risk for having cancer as Toll-like receptors are important for innate immunity. We examined the association between candidate disease-susceptibility polymorphisms in the single nucleotide polymorphism (SNPs) like TLR2 (-196 to-174del), TLR3 (C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes in patients with bladder cancer in a North Indian population.
  
  
  METHODS
  SNPs were comprised of TLR2 (-196 to -174 Del), TLR3(C1377T), TLR4 (Thr399Ile) and TLR9 (G2848A) genes. Allelic and genotypic frequencies of these TLRs SNP from histopathologically confirmed patients of bladder cancer (n = 200) and unrelated healthy controls of similar ethnicity (n = 200) were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis.
  
  
  RESULTS
  In TLR2 I/D gene polymorphism, the combination of ID+DD showed a significant 3-fold increased risk (p = 0.001). TLR2 with heterozygous genotype ID showed a 3-fold risk and combination of heterozygous and variant genotype (ID+DD) also showed a 5-fold risk with tumor stage/grade of patients with bladder cancer. The other genotypes of TLR3, 4 and 9 did not exhibit any significant association with bladder cancer risk.
  
  
  CONCLUSIONS
  Our results suggested the involvement of TLR2 (-196 to-174 del) in bladder cancer susceptibility; however, TLR3, 4 and 9 genes were not associated with risk of bladder cancer, implicating that polymorphisms in these tested TLRs genes are not likely to be associated with increased risk for developing bladder cancer. Functional studies in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in identifying the disease-associated variants for the etiology of bladder cancer.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Science, Lucknow, Uttar Pradesh, India.
authors.forename: Vibha
authors.initials: V
authors.lastname: Singh
authors.forename: Neena
authors.initials: N
authors.lastname: Srivastava
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051193:Toll-Like Receptors / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D051193:Toll-Like Receptors