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

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 gene with prostate cancer risk and provide some justification using analysis. The 157 men with prostate cancer and 145 healthy controls were included in a case-control study. The studied polymorphisms were genotyped using PCR-RFLP method. An 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, = 0.012), c.-31C allele (OR= 1.62, 95 % CI= 1.17-2.26, = 0.004), c.454AG genotype (OR= 2.03, 95 % CI= 1.02-4.04, = 0.043), and c.*148C allele (OR= 1.49, 95 % CI= 1.04-2.15, = 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, = 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, = 0.027) and c.*148T>C (OR= 2.60, 95 % CI= 1.47-4.60, = 0.001) polymorphisms with prostate cancer risk. Finally, analysis revealed that c.-31G>C, which is located in a CpG island of the promoter may change transcriptional regulation of gene and c.454G>A and *148T>C could affect protein structure and possible miRNA interaction with 3'-UTR of 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.