Authors: Bizhani, Fatemeh
Hashemi, Mohammad
Danesh, Hiva
Nouralizadeh, Akbar
Narouie, Behzad
Bahari, Gholamreza
Ghavami, Saeid
Title: Association between single nucleotide polymorphisms in the PI3K/AKT/mTOR pathway and bladder cancer risk in a sample of Iranian population
Language (ISO): en
Abstract: In the past few years several investigations have focused on the role of PI3K/AKT/mTOR pathway and its deregulations in different cancers. This study aimed to examine genetic polymorphisms of this pathway in bladder cancer (BC). In this case-control study, 235 patients with pathologically confirmed bladder cancer and 254 control subjects were examined. PIK3CA, AKT1 and mTOR variants were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The findings proposed that the PIK3CA rs6443624 SNP significantly decreased the risk of BC (OR=0.44, 95 % CI=0.30-0.65, p<0.0001 CA vs CC; OR=0.35, 95 % CI=0.16-0.78, p=0.0107, AA vs CC; OR=0.60, 95 % CI=0.46-0.79, p=0.0002, A vs T). The AKT1 rs2498801 variant is associated with a decreased risk of BC (OR=0.57, 95 % CI=0.39-0.82, p=0.003, AG vs AA; OR=0.74, 95 % CI=0.56-0.97, p=0.032, G vs A) while, AKT1 rs1130233 polymorphism considerably increased the risk of BC (OR=3.70, 95 % CI=2.52-5.43, p<0.0001, GA vs GG; OR=5.81, 95 % CI=1.53-21.97, p=0.010, AA vs GG; OR=2.71, 95 % CI=1.98-3.70, p<0.0001, A vs G). Additionally, mTOR rs2295080 variant notably increased the risk of BC (OR=2.25, 95 % CI=1.50-3.38, p<0.0001, GT vs GG; OR=4.75, 95 % CI=2.80-8.06, p<0.0001, TT vs GG; OR=3.10, 95 % CI=2.34-4.10, p<0.0001, T vs G). None of the other examined polymorphisms (AKT1 rs1130214, AKT1 rs3730358, mTOR rs1883965) revealed significant association with BC. In conclusion, our findings suggest that PIK3CA rs6443624, AKT1 rs2498801, AKT1 rs1130233, as well mTOR rs2295080 polymorphism may be related to bladder cancer development in a sample of Iranian population. Validation of our findings in larger sample sizes of different ethnicities would provide evidence on the role of variants of PI3K/AKT/mTOR pathway in developing BC.
Subject Headings: PIK3CA
Bladder cancer
Issue Date: 2018-01-02
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