title: Associations of PI3KR1 and mTOR polymorphisms with esophageal squamous cell carcinoma risk and gene-environment interactions in Eastern Chinese populations.
abstract: Single nucleotide polymorphisms (SNPs) in the PI3K/PTEN/AKT/mTOR signaling pathway may contribute to carcinogenesis. We genotyped five potentially functional PIK3R1 and mTOR SNPs in 1116 esophageal squamous cell cancer (ESCC) patients and 1117 cancer-free controls to assess their associations with ESCC risk. We observed no association with ESCC risk for any of the selected SNPs. However, the combined analysis of these SNPs revealed that subjects with one-to-three risk genotypes had an increased ESCC risk. Stratified analysis by body mass index (BMI) found that ESCC risk was significantly associated with each of three mTOR SNPs among subjects with BMI < 25.0. Specifically, we found that subjects carrying ≥ 1 risk genotypes had significantly increased ESCC risk, particularly for males, ever-smokers, ever-drinkers, and those with age > 60, or BMI < 25.0. Moreover, three mTOR haplotypes were associated with an increase in ESCC risk. Our meta-analysis of mTOR rs2295080 and cancer risk provided further evidence that mTOR SNPs might modulate cancer susceptibility. In this population, such risk effects might be modified by other risk factors, highlighting the importance of gene-environment interaction in esophageal carcinogenesis. Additional, larger studies are warranted to validate our findings.
authors: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China [3] Molecular Epidemiology Laboratory and Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China.
authors: Jinhong
authors: J
authors: Zhu
authors: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China [2] Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Mengyun
authors: M
authors: Wang
authors: Department of Oncology, Xinhua Hospital affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai, China.
authors: Meiling
authors: M
authors: Zhu
authors: State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Jin
authors: J
authors: He
authors: 1] Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China [2] Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors: Jiu-Cun
authors: JC
authors: Wang
authors: 1] Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China [2] Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors: Li
authors: L
authors: Jin
authors: 1] Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China [2] Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors: Xiao-Feng
authors: XF
authors: Wang
authors: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
authors: Jia-Qing
authors: JQ
authors: Xiang
authors: 1] Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China [2] Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors: Qingyi
authors: Q
authors: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000209:etiology; D016022:Case-Control Studies; D002681:China; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000235:genetics; D004843:Epistasis, Genetic; D004938:Esophageal Neoplasms / Q000209:etiology; D000077277:Esophageal Squamous Cell Carcinoma; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D058570:TOR Serine-Threonine Kinases / Q000235:genetics
chemical_list: D058543:Class Ia Phosphatidylinositol 3-Kinase; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
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