title: Functional promoter rs2295080 T>G variant in MTOR gene is associated with risk of colorectal cancer in a Chinese population.
abstract: BACKGROUND
  The mammalian target of rapamycin (mTOR) plays an important role in the development and progression of colorectal cancer (CRC). Recently, a functional polymorphism (rs2295080 T>G) in the promoter of MTOR has been shown to influence its expression and confer susceptibility to cancer. Therefore, in the present study, we sought to investigate the influence of this polymorphism on the risk of CRC.
  
  
  METHODS
  We genotyped this polymorphism by using the TaqMan method in a case-control study comprising of 737 CRC patients and 777 controls. The logistic regression was used to assess the genetic association with occurrence of CRC. The functionality of the polymorphism was examined by luciferase reporter assay.
  
  
  RESULTS
  We found the variant genotypes of MTOR rs2295080 (TG/GG) were significantly associated with decreased CRC risk, compared with the wild genotype [TG/GG vs. TT: adjusted odds ratio (OR)=0.76, 95% confidence interval (CI)=0.62-0.94, P=0.011], and the protective effect of this polymorphism was more predominant among the subgroups of elder (OR=0.66, 95% CI=0.49-0.89) and male (OR=0.63, 95% CI=0.48-0.84) subjects. Furthermore, the luciferase reporter assay showed that the rs2295080G allele significantly decreased the luciferase activity in both sw480 and sw620 cell lines (P=0.002 and P<0.001, respectively).
  
  
  CONCLUSIONS
  Our results suggest that the functional rs2295080 T>G in the promoter of MTOR may influence the susceptibility of CRC in the Chinese population through regulating the transcription activity of MTOR promoter. Large population-based prospective studies are required to validate our findings.
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Suzhou Center for Disease Prevention and Control, Suzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Developmental Genetics, Nanjing Medical University, Nanjing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Jirong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Pharmaceutics, College of Pharmaceutical Science, Soochow University, Suzhou, China. Electronic address: chendawei@syphu.edu.cn.
authors.forename: Dawei
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, China. Electronic address: zhubl@jscdc.cn.
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000368:Aged; D044466:Asian People; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Colorectal cancer; Polymorphism; mTOR promoter region