Survivin polymorphisms and susceptibility to prostate cancer: A genetic association study and an in Silico analysis

Karimian, M. and Aftabi, Y. and Mazoochi, T. and Babaei, F. and Khamechian, T. and Boojari, H. and Nikzad, H. (2018) Survivin polymorphisms and susceptibility to prostate cancer: A genetic association study and an in Silico analysis. EXCLI Journal, 17. pp. 479-491.

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Survivin is a member of the apoptosis inhibitor protein family and its polymorphisms may lead to susceptibility to cancer. The aim of this study was to investigate the possible association of c.-31G>C (rs9904341), c.454G>A (rs2071214), c.*148T>C (rs2239680) and c.*571T>C (rs1042489) polymorphisms of survivin gene with prostate cancer risk and provide some justification using in silico analysis. The 157 men with prostate cancer and 145 healthy controls were included in a case-control study. The studied polymorphisms were genotyped using PCRRFLP method. An in silico approach was employed to show the possible effects of the polymorphisms on the survivin gene function. The study revealed that there are significant associations between c.-31CC genotype (OR= 2.29, 95 CI= 1.20-4.37, p= 0.012), c.-31C allele (OR= 1.62, 95 CI= 1.17-2.26, p= 0.004), c.454AG genotype (OR= 2.03, 95 CI= 1.02-4.04, p= 0.043), and c.*148C allele (OR= 1.49, 95 CI= 1.04-2.15, p= 0.031) with prostate cancer. Using stratified analysis, we found also significant effects of age distribution on the association of c.-31G>C with prostate cancer risk (OR= 2.10, 95 CI= 1.08-4.10, p= 0.030). Also as a preliminary study, it was shown that smoking status has significant effects on the association of c.-31G>C (OR= 1.94, 95 CI= 1.08- 3.49, p= 0.027) and c.*148T>C (OR= 2.60, 95 CI= 1.47-4.60, p= 0.001) polymorphisms with prostate cancer risk. Finally, in silico analysis revealed that c.-31G>C, which is located in a CpG island of the promoter may change transcriptional regulation of survivin gene and c.454G>A and *148T>C could affect protein structure and possible miRNA interaction with 3'-UTR of survivin transcript respectively. According to the results, c.-31G>C, c.454G>A, and c.*148T>C polymorphisms could be genetic risk factors for prostate cancer in an Iranian population. However, further studies with larger sample size and different ethnicities are required to obtain more comprehensive results. © 2018, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.

Item Type: Article
Additional Information: cited By 5
Uncontrolled Keywords: genomic DNA; microRNA; survivin, 3' untranslated region; adult; aged; allele; Article; cancer risk; case control study; computer model; controlled study; CpG island; DNA extraction; gene function; gene interaction; genetic association study; genetic susceptibility; genotype; human; major clinical study; male; polymerase chain reaction; promoter region; prostate cancer; protein structure; restriction fragment length polymorphism; single nucleotide polymorphism; smoking; survivin gene; very elderly
Subjects: Pathology
Divisions: Faculty of Medicine > Basic Sciences > Department of Pathology& Histology
Depositing User: ART . editor
Date Deposited: 16 Apr 2019 09:07
Last Modified: 16 Apr 2019 09:07

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