Polymorphisms in nitric-oxide synthase 3 may influence the risk of urinary-bladder cancer

Charlotta Ryk1, N Peter Wiklund, Tommy Nyberg

  • 1Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden.

Insights

The NOS3 gene

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Nitric oxide (NO) plays a role in human cancers.
  • Nitric oxide synthase (NOS) enzymes catalyze NO formation.
  • The NOS3 gene encodes endothelial NOS.

Purpose of the Study:

  • To investigate the association between NOS3 gene polymorphisms and urinary-bladder cancer risk and pathogenesis.
  • To analyze the NOS3 promoter -786T>C (rs2070744) and Glu298Asp (rs1799983) polymorphisms.

Main Methods:

  • Genotyping using allelic discrimination and DNA sequencing.
  • Analysis of 359 bladder cancer patients and 164 controls.
  • Correlation of genotypes with tumor stage, grade, progression, and survival.

Main Results:

  • A threefold increased odds ratio for bladder cancer in homozygous carriers of the NOS3 -786T>C promoter polymorphism C allele (p=0.017).
  • No significant association between the NOS3 Glu298Asp polymorphism and bladder cancer risk.
  • An association found between the NOS3 Glu298Asp polymorphism and tumor grade (p=0.040).

Conclusions:

  • The NOS3 promoter polymorphism -786T>C may be a risk factor for bladder cancer.
  • The NOS3 Glu298Asp polymorphism might be associated with bladder cancer progression.

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