Genetic variants of autophagy-related genes in the PI3K/Akt/mTOR pathway and risk of gastric cancer in the Chinese population.

Abstract

Autophagic dysfunction could lead to tumorigenesis and affect tumor progression and prognosis. The PI3K/Akt/mTOR signaling pathway plays an important role in autophagy. The aim of the studies was to explore the association between genetic variants of autophagy-related genes in the PI3K/Akt/mTOR pathway and gastric cancer risk. We selected candidate genes via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO), then used Ensemble, HaploView, and 1000 Genomes Project datasets to extract single nucleotide polymorphisms (SNPs) in the candidate genes. We screened the differently distributed SNPs in 96 gastric cancer patients and 96 healthy controls as candidate SNPs using SNP Array and verified the candidate SNPs in 622 patients and 622 healthy controls using time-of-flight mass spectrometry. Candidate SNPs located in, IRS1 (rs10205233 C>T), PIK3CD (rs3934934 A>G), PIK3R1 (rs706711 A>G), and AKT1 (rs35285446 ->T), were selected. IRS1 (rs10205233 C>T) was significantly associated with gastric cancer risk (adjusted OR=0.76, 95%CI=0.59-0.97, p=0.031 in co-dominant model; adjusted OR=0.76, 95%CI=0.60-0.97, p=0.029 in dominant model). There were no significant associations between the rest of candidate SNPs and gastric cancer risk. The IRS1 (rs10205233 C>T) could be a specific biomarker for gastric cancer patients in Xianyou County, a rural area with a high prevalence of gastric cancer in Fujian Province.