Genetic variations in the mTOR gene contribute toward gastric adenocarcinoma susceptibility in an Eastern Chinese population.
OBJECTIVE
Genetic variants in the mammalian target of rapamycin (mTOR) gene have become an interesting topic for the study of genetic susceptibility to cancer, but their associations with the risk of gastric cancer have not been fully investigated.


METHODS
In a hospital-based case-control study of 1002 gastric cancer patients and 1003 cancer-free controls, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) (rs1034528G>C, rs17036508T>C, rs3806317A>G, and rs2295080T>G) of mTOR and assessed their associations with the risk of gastric cancer using univariate and multivariate logistic regression analyses. We also used the multifactorial dimension reduction analysis to explore possible interactions and the false-positive report probabilities to assess significant findings.


RESULTS
We found that rs1034528 CG/CC and rs3806317 GA/GG variant genotypes were associated with an increased risk of gastric cancer under a dominant model (adjusted odds ratio=1.27 and 1.22, respectively). In the combined analysis of all four SNPs under investigation, patients with 3-4 risk genotypes of mTOR had a significantly increased risk of gastric cancer (adjusted odds ratio=1.46, 95% confidence interval=1.19-1.79) compared with those with 0-2 risk genotypes. Stratified analysis indicated that this risk was more pronounced in subgroups of men, never-smokers, never-drinkers, and clinical stages III+IV. The multifactorial dimension reduction analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer.


CONCLUSIONS
These findings suggest that potentially functional SNPs of mTOR may individually or collectively contribute to the risk of gastric cancer. Larger studies with diverse ethnic populations are warranted to validate our findings.
aCancer Institute, Collaborative Innovation Center for Cancer Medicine bDepartment of Medical Oncology cDepartment of Abdominal Surgery dDepartment of Pathology, Fudan University Shanghai Cancer Center eDepartment of Oncology, Shanghai Medical College fMinistry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai gState Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangdong hFudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China iDuke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA.
Meng-Yun
MY
Wang
Qiao-Xin
QX
Li
Jing
J
He
Li-Xin
LX
Qiu
Ya-Nong
YN
Wang
Jin
J
Li
Meng-Hong
MH
Sun
Xiao-Feng
XF
Wang
Ya-Jun
YJ
Yang
Jiu-Cun
JC
Wang
Li
L
Jin
Qing-Yi
QY
Wei
D000230:Adenocarcinoma / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002460:Cell Line; D002681:China; D005260:Female; D015870:Gene Expression; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
D012333:RNA, Messenger; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases