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.
Medeiros
R
R
Molecular Oncology Unit, Instituto Português de Oncologia, R. Dr. Ant. Bernardino Almeida, 4200-072, Porto, Portugal. mop06210@mail.telepac.pt
Morais
A
A
Vasconcelos
A
A
Costa
S
S
Pinto
D
D
Oliveira
J
J
Lopes
C
C
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