The endothelial nitric oxide synthase Glu-298-Asp polymorphism and its mRNA expression in the peripheral blood of patients with prostate cancer and benign prostatic hyperplasia.
BACKGROUND
The endothelial nitric oxide synthase (ecNOS) has an important role in vascular development and in the carcinogenesis process of prostate cancer (PCa). The nitric oxide (NO) production may promote cancer progression by providing a selective growth advantage to tumor cells, by angiogenic stimulus and by direct DNA damage.


METHODS
The present study aimed at evaluating the ecNOS Glu-298-Asp polymorphism by the PCR-RFLP technique, associating genotypes with gene expression levels and the tumor biomarker, Prostate Cancer Antigen (DD3), through semi-quantitative RT-PCR. Pre-surgical peripheral blood samples from 160 patients were analyzed: 84 PCa, 11 prostate intraepithelial neoplasia (PIN) and 65 benign prostatic hyperplasia (BPH).


RESULTS
The GG and GT Glu-298-Asp genotypes were associated with positive DD3 expression in the peripheral blood, presenting a 3.32-fold higher risk of PCa occurrence. There was no association between genotypes and ecNOS mRNA expression levels; however, the presence of the G allele is closely related to the hematogenous dissemination event of tumoral cells, as evidenced by the DD3 positivity. The higher G allele frequency among pT3 and pT4 staged PCa patients suggests that this would be associated with advanced phenotypes of the disease and may also be contributing to higher NO levels, causing cancer progression.


CONCLUSIONS
The G allele may have a secondary influence on the prostate cancer predisposition, but an essential role on the event of tumor cells hematogenous dissemination, probably due to the angiogenic stimulus.
Marangoni
Karina
K
Federal University of Uberlândia, Institute of Genetics and Biochemistry, Molecular Genetics Laboratory, Campus Umuarama, Block 2E, Room 24, 38400-902 Uberlândia, MG, Brazil.
Neves
Adriana F
AF
Cardoso
Alexandra M
AM
Santos
Weruska Karyna
WK
Faria
Paula C
PC
Goulart
Luiz R
LR
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005838:Genotype; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011470:Prostatic Hyperplasia / Q000097:blood*; D019048:Prostatic Intraepithelial Neoplasia / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood*; D012333:RNA, Messenger / Q000097:blood*
D000951:Antigens, Neoplasm; D012333:RNA, Messenger; C479341:prostate cancer antigen 3, human; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III