Ser608Leu polymorphisms in the nitric oxide synthase-2 gene may influence urinary bladder cancer pathogenesis

Charlotta Ryk, N. Peter Wiklund, Tommy Nyberg, Petra J. De Verdier

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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. Material and 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.

Original languageEnglish
Pages (from-to)319-325
Number of pages7
JournalScandinavian Journal of Urology and Nephrology
Issue number5
StatePublished - Nov 2011
Externally publishedYes


  • genetic polymorphisms
  • nitric oxide
  • nitric oxide synthase-2
  • urinary bladder cancer


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