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Outcome in Prostate Cancer

Association with Endothelial Nitric Oxide Synthase Glu-Asp298 Polymorphism at Exon 7¹

Molecular Oncology Unit and Department of Urology, Instituto Português de Oncologia, Porto, 4200-072, Portugal

Purpose: 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.

Experimental Design: 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.

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