Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer.
The endothelial cell-specific form of nitric oxide synthases (ecNOS) is localized at 7q35-q36 and is involved in vascular development and tumour growth in human prostate cancer. We have conducted a case-control study to investigate the prevalence of two polymorphisms at intron 4 (ecNOS4a/b) and exon 7 (Glu-Asp298) of ecNOS gene in 125 prostate cancer (PCa) patients and in 153 controls. We observed that the a-allele (aa or ab genotypes from ecNOS4a/b) was over-presented in the group of PCa with Gleason histological grade >or=7 (P=0.041). With regard to the Glu-Asp298 polymorphism, patients with the T-allele were younger than patients with no T-allele (P=0.037), and a statistically significant difference was noted in the Glu-Asp298 genotype distribution between cases with advanced disease and cases with localized disease (P=0.0013). When comparing cases and controls with logistic regression analysis we observed that the presence of the a-allele is associated with prostate cancer risk (odds ratio (OR) 1.83; 95% confidence interval (CI) 1.06-3.17; P=0.029), to high histological grade (Gleason >or=7) of PCa (OR 2.18; 95% CI 0.95-4.98; P=0.062) and with the risk of progression of the cancer disease (OR 2.85; 95% CI 1.19-6.82; P=0.018). Furthermore, we found that carriers with the combination of the a-allele (aa and ab ecNOS4a/b genotypes) and T-allele (GT and TT from Glu-Asp298) have a threefold increase in prostate cancer risk (OR 3.13; 95% CI 1.41-6.91, P=0.004). In summary, we have identified an NO-related genetic risk factor for prostate cancer that may help in understanding the molecular mechanism involved in the individual susceptibility to prostate cancer.
Molecular Oncology Unit, Instituto Português de Oncologia, R. Dr. Ant. Bernardino Almeida, 4200-072, Porto, Portugal. mop06210@mail.telepac.pt
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004727:Endothelium / Q000201:enzymology; D005091:Exons; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*; D012307:Risk Factors
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III