Survivin polymorphisms and susceptibility to prostate cancer
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Date
2018-05-18
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a genetic association study and an in silico analysis
Abstract
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.
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Keywords
Prostate cancer, Survivin gene, Genetic polymorphism, In silico analysis