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Cancer Lett. 2003 Jan 10;189(1):85-90.

Endothelial nitric oxide synthase gene polymorphisms and the shedding of circulating tumour cells in the blood of prostate cancer patients.

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Molecular Oncology Unit, Laboratórios-PISO 4, Instituto Português de Oncologia, Porto, Rua Dr. António Bernardino Almeida, 4200-072 Porto, Portugal.


The involvement of endothelial nitric oxide synthase (ecNOS) gene polymorphisms (ecNOS4a/b and Glu-Asp298) on the shedding of tumor cells in the blood of 61 patients with prostate cancer (PCa), was analyzed. Hematogenous micrometastasis with blood circulating tumor cells (CTCs) may be an early event in the natural history of PCa metastization. CTCs can be detected by the presence of messenger RNA prostate specific membrane antigen by reverse transcription-polymerase chain reaction. We found an association between ecNOS4a/b genotypes presenting the a allele (ab/aa) with the presence of CTCs in the blood of PCa under the age of 67 years (P=0.003) and with localized disease (P=0.012). This association was not found for Glu-Asp298 genotypes. In summary, we have identified a nitric oxide related genetic factor associated with micrometastization of prostate cancer. We hypothesize that genotypes with the a allele of the ecNOS4a/b polymorphism may facilitate the survival of CTCs in the blood of cancer patients.

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