Purpose: Excessive activation of PI3K/AKT/mTOR signaling pathway is one of the most common changes in human cancers, and single nucleotide polymorphisms (SNPs) existing in its functional region can affect the occurrence process of a variety of cancers. This study aimed to screen out the SNPs associated with susceptibility to gastric cancer in the PI3K/AKT/mT0R signaling pathway.
Methods: In this case-control study, the tagging SNPs in the promoter region5'-UTR, exon region or 3'-UTR of PIK3CA, PIK3CB, PIK3R1, PIK3R2, PIK3R3, AKT1, AKT2, AKT3 and mTOR genes were screened out. The relationship between the genetic variation of PI3K/AKT/mT0R signaling pathway genes and the susceptibility to gastric cancer in Chinese Han population was investigated by this casecontrol study.
Results: The results showed that the polymorphisms of the two loci, PIK3R3 rs7536272 (Additive model: OR=1.16, 95% CI=1.01-1.35) and mTOR rs2295080 (GG vs TT: OR=0.75, 95% CI=0.60-0.94; Additive model: OR=0.78, 95% CI=0.66- 0.93), were associated with the risk of gastric cancer in the studied population and there was a combined effect between the two loci (ptrend=0.005).
Conclusions: In conclusion, the polymorphisms of the two loci, PIK3R3 rs7536272 and mTOR rs2295080, on the PI3K/AKT/mTOR signaling pathway genes are associated with genetic susceptibility to gastric cancer in Chinese population.