Association of KLK3 , VAMP8 and MDM4 Genetic Variants within microRNA Binding Sites with Prostate Cancer: Evidence from
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ORIGINAL ARTICLE
Association of KLK3, VAMP8 and MDM4 Genetic Variants within microRNA Binding Sites with Prostate Cancer: Evidence from Serbian Population Nevena Kotarac 1 & Zorana Dobrijevic 1 & Suzana Matijasevic 1 & Dusanka Savic-Pavicevic 1 & Goran Brajuskovic 1 Received: 22 January 2020 / Accepted: 10 June 2020 # Arányi Lajos Foundation 2020
Abstract A growing number of studies have suggested that genetic variants affecting the micro-RNA- binding mechanisms (miRSNPs) constitute a promising novel class of biomarkers for prostate cancer (PCa) biology. Among the most extensively studied miRSNPs in the context of cancer is the variation rs4245739 in the MDM4 gene, while a recent large-scale analysis revealed significant differences in genotype distributions between aggressive and non-aggressive disease for rs1058205 in KLK3 and rs1010 in VAMP8. In this study, we examined a total of 1083 subjects for these three variants using Taqman® SNP Genotyping Assays. Three hundred and fifty-five samples of peripheral blood were obtained from patients with PCa and 358 samples from patients with benign prostatic hyperplasia (BPH). The control group consisted of 370 healthy volunteers. Comparisons of genotype distributions among PCa and BPH patients, as well as between PCa patients and healthy controls, yielded no evidence of association between the analyzed genetic variants and the risk of developing PCa. However, all three tested genetic variants have shown the association with the parameters of PCa progression. For KLK3 variant rs1058205, minor allele C was found to associate with the lower serum PSA score in PCa patients (PSA > 20 ng/ml vs. PSA < 10 ng/ml comparison, Prec = 0.038; ORrec = 0.20, 95%CI 0.04–1.05). The obtained results point out the potential relevance of the tested genetic variants for the disease aggressiveness assessment. Keywords miRSNPs . rs1058205 . rs1010 . rs4245739 . Prostate cancer
Introduction Prostate cancer (PCa), the second most frequent malignancy in men worldwide, accounted 1.276.106 new cases and caused 358.989 deaths (6.7% of all deaths caused by cancer in men) in 2018 [1]. The well-established risk factor for PCa, apart from age and ethnicity, is family-history of the disease [2]. Rarely occurring but high-penetrant genetic variants, as well as commonly occurring low-risk variants, both contribute to genetic basis of PCa. Genome wide association studies (GWASs) have been invaluable in the discovery of these common variants associated with PCa susceptibility. In the largest PCa GWAS to date and the meta-analysis reported recently * Goran Brajuskovic [email protected] 1
Centre for Human Molecular Genetics, Faculty of Biology, University of Belgrade, Belgrade, Serbia
[3], 63 novel PCa susceptibility loci were identified, which raised the total number of known loci from GWAS to around 170 (GWAS Catalog) [4]. However, these commonly occurring low-risk variants can explain only about 28.4% of the familial relative risk for PCa, suggesting that additional SNPs remain to be identified [3
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