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

Urology Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Scandinavian Journal of Urology and Nephrology (Impact Factor: 1.24). 05/2011; 45(5):319-25. DOI: 10.3109/00365599.2011.584901
Source: PubMed


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.
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.
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.
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.

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    ABSTRACT: Nitrinergic control is important in meal-induced satiety. The aim of this study was to assess functional polymorphisms in nitric oxide synthase (NOS) genes in the susceptibility to functional dyspepsia (FD). Genomic DNA from 89 patients with FD and 180 healthy subjects matched for age and gender were typed for the gene of neuronal NOS (nNOS, rs2682826), inducible NOS (iNOS, rs2297518) and a variable number tandem repeat in intron 4 of endothelial NOS (eNOS). Patients ingested 500 mL of Ensure(®) during a 20 min period and dyspeptic symptoms were scored. Genotype frequencies of eNOS and iNOS were not significantly different between FD patients and controls. The frequency of the T allele in nNOS was significantly higher in FD patients compared to the controls (49 vs. 16 %; odds ratio 5.01; 95 % confidence interval 2.83-9.01; p < 0.05). Patients with the T allele in the nNOS polymorphism reported a higher satiation score than those with the CC genotype during the nutrition drink test (median 179 vs. 117; p < 0.05). The nNOS gene polymorphism is associated with susceptibility to FD and influences satiation in FD patients. Our data support the importance of NOS gene polymorphisms in the pathogenesis of FD.
    Digestive Diseases and Sciences 10/2013; 59(1). DOI:10.1007/s10620-013-2886-4 · 2.61 Impact Factor

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