title: Ser608Leu polymorphisms in the nitric oxide synthase-2 gene may influence urinary bladder cancer pathogenesis.
abstract: OBJECTIVE
  The aim of this study was to analyse whether the exonic Ser608Leu (rs2297518) polymorphism in nitric oxide synthase-2 (NOS2) influences urinarybladder cancer risk and pathogenesis.
  
  
  METHODS
  Genotyping of 359 bladder cancer patients from a population-based cohort and 164 population controls was carried out by allelic discrimination and sequencing. Genotypes were combined with information on tumour stage, grade, stage progression and cancer-specific death, from a 5-year clinical follow-up.
  
  
  RESULTS
  For the Ser608Leu polymorphism, TT homozygotes had three-fold higher odds for bladder cancer (p = 0.081), but once ill, a lower risk for stage progression (p = 0.031) and a better prognosis.
  
  
  CONCLUSIONS
  The data indicate that the Tallele of the NOS2 Ser608Leu polymorphism is an initial risk factor for developing urinary bladder cancer. Among bladder cancer patients, however, individuals who are TT homozygous have a lower risk of developing muscle-invasive disease and a higher cancer-specific survival. Depending on the cellular context, nitric oxide can induce proliferation as well as apoptosis. The results from this and previous studies suggest that NOS2 polymorphisms may influence both the risk of contracting bladder cancer and the aggressiveness of the disease.
authors: Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors: Charlotta
authors: C
authors: Ryk
authors: N Peter
authors: NP
authors: Wiklund
authors: Tommy
authors: T
authors: Nyberg
authors: Petra J
authors: PJ
authors: De Verdier