Genetic variations of mTORC1 genes and risk of gastric cancer in an eastern chinese population
- 19 February 2013
- journal article
- research article
- Published by Wiley in Molecular Carcinogenesis
- Vol. 52 (S1), 70-79
- https://doi.org/10.1002/mc.22013
Abstract
Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions, and genetic variations in this complex may affect cancer risk. In this study, we examined the associations between eight potential functional single nucleotide polymorphisms in the mTORC1 genes (rs2536T>C and rs1883965G>A for mTOR, rs3160T>C, and rs26865A>G for mLST8, rs3751934C>A, rs1062935T>C, rs3751932T>C, and rs12602885G>A for Raptor, not included in published gastric cancer genome‐wide association studies) and gastric cancer risk in 1125 gastric cancer cases and 1196 cancer‐free controls. We performed conditional logistic regression and multifactor dimensionality reduction (MDR) analyses to assess their associations with gastric cancer risk. We also used false‐positive report probabilities (FPRP) for assessing significant findings. We found that only the rs1883965A variant genotypes were associated with an increased risk of gastric cancer (AG vs. GG: adjusted odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.00–1.59; AA vs. GG: adjusted OR = 1.85, 95% CI = 0.67–5.16 and dominant model: adjusted OR = 1.28, 95% CI = 1.03–1.61). Patients with ≥1 risk genotypes of mTOR had significant increased risk (adjusted OR = 1.25, 95% CI = 1.04–1.49), compared with those having zero risk genotypes. In the stratified analysis, the risk effect of the rs1883965 AG/AA genotypes was evident in subgroups of ever‐smokers, non‐gastric cardia adenocarcinoma and clinical stage I + II, which were noteworthy findings as evaluated by FPRP. The MDR analysis identified smoking status and rs1883965 as the strongest two‐factors for gastric cancer risk. These data support the hypothesis that functional polymorphisms of mTOR may contribute to gastric cancer risk. Clearly, our results require validation in larger studies with different ethnic populations.Keywords
This publication has 38 references indexed in Scilit:
- Meat Intake and Risk of Stomach and Esophageal Adenocarcinoma Within the European Prospective Investigation Into Cancer and Nutrition (EPIC)JNCI Journal of the National Cancer Institute, 2006
- Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC–EURGAST)International Journal of Cancer, 2006
- TOR Signaling in Growth and MetabolismCell, 2006
- Cellular Mucosal Defense During Helicobacter pylori Infection: A Review of the Role of Glutathione and the Oxidative Pentose PathwayHelicobacter, 2005
- Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in ChinaInternational Journal of Cancer, 2004
- mTOR Is Essential for Growth and Proliferation in Early Mouse Embryos and Embryonic Stem CellsMolecular and Cellular Biology, 2004
- Helicobacter pylori Infection and Gastric Atrophy: Risk of Adenocarcinoma and Squamous-Cell Carcinoma of the Esophagus and Adenocarcinoma of the Gastric CardiaJNCI Journal of the National Cancer Institute, 2004
- Smoking and the risk of gastric cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC)International Journal of Cancer, 2003
- The phosphatidylinositol 3-Kinase–AKT pathway in human cancerNature Reviews Cancer, 2002
- Body Mass Index and Risk of Adenocarcinomas of the Esophagus and Gastric CardiaJNCI Journal of the National Cancer Institute, 1998