title: Genetic variations of mTORC1 genes and risk of gastric cancer in an Eastern Chinese population.
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.
authors: Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Jing
authors: J
authors: He
authors: Meng-Yun
authors: MY
authors: Wang
authors: Li-Xin
authors: LX
authors: Qiu
authors: Mei-Ling
authors: ML
authors: Zhu
authors: Ting-Yan
authors: TY
authors: Shi
authors: Xiao-Yan
authors: XY
authors: Zhou
authors: Meng-Hong
authors: MH
authors: Sun
authors: Ya-Jun
authors: YJ
authors: Yang
authors: Jiu-Cun
authors: JC
authors: Wang
authors: Li
authors: L
authors: Jin
authors: Ya-Nong
authors: YN
authors: Wang
authors: Jin
authors: J
authors: Li
authors: Hong-Ping
authors: HP
authors: Yu
authors: Qing-Yi
authors: QY
authors: Wei
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000230:Adenocarcinoma / Q000453:epidemiology / Q000209:etiology*; D044466:Asian People / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008875:Middle Aged; D046912:Multiprotein Complexes / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D000076223:Regulatory-Associated Protein of mTOR; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000209:etiology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D000076242:mTOR Associated Protein, LST8 Homolog
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C555285:MLST8 protein, human; D046912:Multiprotein Complexes; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; D000076242:mTOR Associated Protein, LST8 Homolog; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: gastric adenocarcinoma; genetic susceptibility; mTORC1; polymorphism