P0217 Potentially functional polymorphisms in the mTOR gene and gastric adenocarcinoma susceptibility in an eastern Chinese population

Abstract

Background mTOR is an important intracellular mediator involved in the PI3K/AKT signalling pathway and a critical regulator of cell growth and proliferation in response to environmental and nutritional conditions. We evaluated potentially functional polymorphisms in the 5′ untranslated region (UTR) of the mTOR gene associated with the risk of gastric cancer. Methods In this case–control study with 1123 patients and 1113 healthy controls matched for age and gender, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) located in 5′ UTR of the mTOR gene and evaluated their association with risk of gastric cancer. Findings In individual polymorphism analysis, the rs1034528 G > C was associated with 1.21-times increased risk of gastric cancer under a dominant model (adjusted odds ratio 1.21, 95% confidence interval [CI] 1.01–1.46). When the four polymorphisms were combined, the risk of gastric cancer increased in a dose-dependent manner as the number of risk genotypes increased (ptrend = 0.001). Patients with three or four risk genotypes had a significantly higher risk of gastric cancer than those with 0–2 risk genotypes (adjusted odds ratio 1.41, 95% CI 1.15–1.73). Stratification analysis indicated that the combined effect of risk genotypes was more evident in subgroups of older age (>59 years), men, smokers, non-drinkers, patients with gastric cardia adenocarcinoma, and those with clinical stage III and IV disease. Further analysis using mRNA expression data from the HapMap project suggested that both CG and CC carriers of rs1034528 G > C were associated with non-significantly decreased expression of mTOR mRNA in normal cell lines from 45 Chinese patients (p = 0.97 for CG carriers, p = 0.38 for CC carriers). Interpretation Functional mTOR variants may contribute to the risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate these findings.