Association between AKT1 polymorphisms and susceptibility to breast cancer in the Iranian population

BackgroundAkt1, a crucial component of the PI3K/Akt signaling pathway, mediates a plethora of cancer-related processes such as cell growth, proliferation, survival, apoptosis and invasion. So, the pathogenesis of various types of cancer may be attributed to single nucleotide polymorphisms (SNPs) in the AKT1 gene. Here, we aimed to investigate whether AKT1 rs1130214, rs1130233 and rs2494732 SNPs are associated with an increased risk of breast cancer (BC).Material and methodsA total of 100 women diagnosed with BC and 100 healthy controls were included. The AKT1 SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system PCR (ARMS-PCR) methods. Using logistic regression analysis, the genotypic and allelic associations between AKT1 SNPs and BC development were determined under co-dominant, dominant, and recessive inheritance models. Genotype combination and haplotype analysis were also performed to assess the combined effect of the AKT1 SNPs on the risk of BC. We used RNAsnp online server to predict the effect of rs1130233 SNP on local RNA secondary structure.ResultsThe rs1130233 SNP was observed to be significantly associated with predisposition to BC under recessive inheritance model (p < 0.05). The rs1130233 T allele confers risk of developing BC (OR: 1.877; 95% CI: 1.242-2.837; p = 0.003). For rs1130214/rs2494732 and rs1130233/rs2494732, AA/TC and CC/TC combined genotypes were found to be independently associated with reduced risk of BC, respectively. We also found that individuals with the CTC haplotype have an increased risk of BC (p < 0.05).ConclusionOur results highlight that AKT1 rs1130233 SNP is significantly associated with a higher risk of BC. Furthermore, the CTC haplotype can be utilized to identify individuals with a genetic susceptibility to BC.