Endothelial nitric oxide synthase gene polymorphisms and prostate cancer risk in Serbian population

Abstract

Genome-wide association studies (GWAS) have identified over 46 SNPs associated with human prostate cancer (PCa). Some studies have shown correlation of the nitric oxide synthase (NOS) NOS3 gene polymorphisms with the risk and/or progression of PCa. This study aimed to evaluate the association of NOS3 gene polymorphisms (-786T>C, -764A>G, -714G>T, -690C>T, -649G>A and 894G>T) with PCa risk and progression. 150 patients with PCa, 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 PCa 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 NOS3 -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 T3 and T4 (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 NOS3 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 PCa and patient outcome.

Genetic Variants within Endothelial Nitric Oxide Synthase Gene and Prostate Cancer: A Meta-Analysis

“…These studies focused mainly on the effect of variants located in the coding region, introns, and the promoter of NOS3 on PCa susceptibility and the association of these variants with standard prognostic parameters of PCa progression. Two most commonly analyzed single nucleotide variants are rs1799983 located in the seventh exon and rs2070744 in the promoter of this gene . Furthermore, an the insertion–deletion variant 4a/b in an intron of this gene was evaluated as potential PCa‐associated genetic marker …”

The G894t, T‐786c and 4b/a polymorphisms in Enos gene and cancer risk: a meta‐analysis

“…The distribution of genotypes in the controls of all the included studies was in agreement with HWE, except two studies . In addition, a different case‐control set up of prostate cancer, prostate cancer versus benign prostate hyperplasia (BPH), was used for three included studies ( eNO S G894T) and for one study ( eNOS T‐786C) , respectively (Table ).…”

Nitric Oxide Synthase in Male Urological and Andrologic Functions

“…A plethora of metaanalyses has identified eNOS gene polymorphisms as strong susceptibility factors for the progression toward prostate carcinoma [120]. Another study also reported that NOS3 gene Nitric Oxide Synthase -Simple Enzyme-Complex Rolespolymorphisms were genetic susceptibility factors for the progression of prostate carcinoma and poor patient outcomes [121]. A meta-analysis conducted by Zhao et al suggested that eNOS gene 894G > T polymorphism contributed to aggravate the onset of prostate carcinoma in males [122].…”