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Endothelial nitric oxide synthase gene polymorphisms and prostate cancer risk in S erbian population
Author(s) -
Branković Ana,
Brajušković Goran,
Nikolić Zorana,
Vukotić Vinka,
Cerović Snežana,
SavićPavićević Dušanka,
Romac Stanka
Publication year - 2013
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12045
Subject(s) - genotype , allele , genotyping , biology , prostate cancer , genetics , snp , medicine , single nucleotide polymorphism , genetic model , gastroenterology , oncology , cancer , gene
Summary Genome‐wide association studies ( GWAS ) have identified over 46 SNP s associated with human prostate cancer (PCa). Some studies have shown correlation of the nitric oxide synthase (NOS) NOS 3 gene polymorphisms with the risk and/or progression of PCa. This study aimed to evaluate the association of NOS 3 gene polymorphisms (−786T>C, −764A>G, −714G>T, −690C>T, −649G>A and 894G>T) with PC a risk and progression. 150 patients with PC a, 150 patients with BPH and 100 age‐matched healthy controls were recruited in this study. Genotyping of promoter polymorphisms was performed by bi‐directional DNA sequencing, and for 894G>T by RFLP analysis. There was no significant association between the alleles and genotypes of these genetic variants and PC a risk. For −786T>C polymorphism, we found that C allele is associated with absence of metastases, assuming dominant genetic model ( P = 0.049; OR , 0.50; 95% CI , 0.25–1.00). It was found that, compared with NOS 3 −690C>T variant CC genotype, CT and TT genotypes confer decreased risk of developing metastases (dominant model, P = 0.015, OR , 0.24; 95% CI , 0.07–0.88) and show association with low clinical tumour stage, compared with stages T 3 and T 4 (dominant model, P = 0.046, OR , 0.20; 95% CI , 0.04–1.02). Genetic variants −764A>G, −714G>T, −649G>A were not detected in our study group. There is evidence of an inverse correlation of the NOS 3 894G>T minor allele with high serum PSA (>20 ng/ml) (dominant model, P = 0.013, OR , 0.37; 95% CI , 0.17–0.82). Our results suggest that NOS3 gene polymorphisms are genetic susceptibility factors for the progression of PC a and patient outcome.