Outcome in prostate cancer: association with endothelial nitric oxide synthase Glu-Asp298 polymorphism at exon 7.
OBJECTIVE
The endothelial cell-specific form of nitric oxide synthases (ecNOS) was mapped at 7q35-q36 and plays an important role in vascular development and tumor growth in human prostate cancer. Bone metastasis, clinical T-stage, tumor grade, and serum prostate-specific antigen (PSA) have been shown to have prognostic importance in the outcome of prostate cancer. The purpose of this study was to evaluate ecNOS polymorphism as a genetic indicator of the outcome of the disease.


METHODS
In this study, we characterized the Glu-Asp298 ecNOS polymorphism in a series of 161 prostate cancer cases. Logistic regression models were used to assess the contribution of these genotypes to prostate cancer progression.


RESULTS
For Glu-Asp298 polymorphism, we found that GG genotype was associated to advanced disease [P = 0.020; odds ratio (OR), 2.12; 95% confidence interval (CI), 1.12-4.03] and bone metastasis (P = 0.038; OR, 2.23; 95% CI, 1.03-4.84). Furthermore, after logistic regression analysis with step-wise routine to identify predictive parameters of metastasis, which included age at diagnosis, advanced stage, GG genotype, high grade, and high serum PSA, we observed that Glu-Asp298-GG genotype (P = 0.004; OR, 7.4; 95% CI, 1.87-29.26), high grade tumor (P = 0.009; OR, 6.15; 95% CI, 1.56-24.17), and high serum PSA (P < 0.001; OR, 245.12; 95% CI, 19.93-3013.90) were significantly associated with bone metastasis.


CONCLUSIONS
This study demonstrates a strong association between Glu-Asp298-GG genotype as a nitric oxide-related genetic factor and advanced disease and bone metastasization. The establishment of a genetic profile for each patient may be useful in the prediction of the outcome of prostate cancer patients.
Medeiros
Rui M
RM
Molecular Oncology Unit and Department of Urology, Instituto Português de Oncologia, Porto, 4200-072, Portugal. mop06210@mail.telepac.pt
Morais
Antonio
A
Vasconcelos
André
A
Costa
Sandra
S
Pinto
Daniela
D
Oliveira
Jorge
J
Ferreira
Paula
P
Lopes
Carlos
C
D000368:Aged; D001224:Aspartic Acid / Q000737:chemistry; D001859:Bone Neoplasms / Q000556:secondary; D018450:Disease Progression; D005091:Exons; D005838:Genotype; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D016896:Treatment Outcome
D001224:Aspartic Acid; D018698:Glutamic Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III