title: A polymorphism (rs2295080) in mTOR promoter region and its association with gastric cancer in a Chinese population.
abstract: BACKGROUND
  As an imperative part of PI3K/Akt/mTOR pathway, mammalian target of rapamycin (mTOR) has been demonstrated to increase in gastric cancer cells and tumors. Our research explored the relationship between single nucleotide polymorphism (SNP) rs2295080 in mTOR promoter region and the risk of gastric cancer (GC).
  
  
  METHODS
  Seven hundred and fifty-three (753) gastric adenocarcinoma patients and 854 matched healthy subjects were recruited in the cancer association study and 60 tissues were used to test the expression of mTOR. Unconditional logistic regression was selected to evaluate the association between the rs2295080 T>G polymorphism and GC risk. We then examined the functionality of this promoter genetic variant by luciferase assay and EMSA.
  
  
  RESULTS
  Individuals with G allele had a 23% decreased risk of GC, comparing with those carrying T allele (adjusted OR = 0.77, 95% CI = 0.65-0.92). This protective effect of G allele stood out better in male group. Meanwhile, GC patients carrying TG/GG genotype also displayed a decreased mRNA level of mTOR (P = 0.004). In luciferase assay, T allele tended to enhance the transcriptional activity of mTOR with an approximate 0.5-fold over G allele. Furthermore, EMSA tests explained that different alleles of rs2295080 displayed different affinities to some transcriptional factor.
  
  
  CONCLUSIONS
  The mTOR promoter polymorphism rs2295080 was significantly associated with GC risk. This SNP, which effectively influenced the expression of mTOR, may be a new biomarker of early diagnosis of gastric cancer and a suitable indicator of utilizing mTOR inhibitor for treatment of GC.
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Guoquan
authors.initials: G
authors.lastname: Tao
authors.forename: Meiyun
authors.initials: M
authors.lastname: Kang
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhu
authors.forename: Weida
authors.initials: W
authors.lastname: Gong
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wu
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
references.citation: Mol Cell Biol. 2004 Jan;24(1):200-16
references.pmid: 14673156
references.citation: J Biol Chem. 2012 Jan 13;287(3):2090-8
references.pmid: 22139837
references.citation: Cancer. 2009 May 15;115(10 Suppl):2313-20
references.pmid: 19402072
references.citation: Int J Cancer. 2012 Feb 1;130(3):491-6
references.pmid: 21898386
references.citation: Lancet. 2009 Aug 8;374(9688):477-90
references.pmid: 19625077
references.citation: Int J Cancer. 2011 Sep 1;129(5):1207-13
references.pmid: 21064099
references.citation: Expert Opin Investig Drugs. 2009 Sep;18(9):1333-49
references.pmid: 19678801
references.citation: Clin Cancer Res. 2006 Dec 15;12(24):7215-20
references.pmid: 17189392
references.citation: Mol Biol Cell. 2002 Jul;13(7):2276-88
references.pmid: 12134068
references.citation: Am J Physiol Cell Physiol. 2011 Jul;301(1):C213-26
references.pmid: 21508335
references.citation: PLoS One. 2011;6(7):e21415
references.pmid: 21750711
references.citation: Cancer Biol Ther. 2006 Sep;5(9):1065-73
references.pmid: 16969122
references.citation: Crit Rev Oncol Hematol. 2007 Aug;63(2):172-82
references.pmid: 17540577
references.citation: Lung Cancer. 2011 Jan;71(1):82-8
references.pmid: 20447721
references.citation: Leuk Lymphoma. 2012 May;53(5):947-51
references.pmid: 21973240
references.citation: J Cancer Res Clin Oncol. 2009 Jan;135(1):29-38
references.pmid: 18523800
references.citation: Carcinogenesis. 2010 Sep;31(9):1604-11
references.pmid: 20622004
references.citation: Dig Dis. 2011;29(3):310-5
references.pmid: 21829022
references.citation: Mol Cell Neurosci. 2011 Jun;47(2):145-53
references.pmid: 21463685
references.citation: Carcinogenesis. 2009 Dec;30(12):2047-52
references.pmid: 19875696
references.citation: PLoS One. 2012;7(11):e50302
references.pmid: 23209702
references.citation: J Clin Oncol. 2009 Feb 20;27(6):857-71
references.pmid: 19164214
references.citation: Curr Oncol Rep. 2011 Oct;13(5):398-406
references.pmid: 21755275
references.citation: Cell Res. 2007 Aug;17(8):666-81
references.pmid: 17680028
references.citation: Curr Opin Cell Biol. 2005 Dec;17(6):596-603
references.pmid: 16226444
references.citation: Endocr Relat Cancer. 2012 Jan 09;19(1):1-12
references.pmid: 21903859
references.citation: Blood. 2011 Dec 22;118(26):6803-13
references.pmid: 22053105
references.citation: Tumour Biol. 2011 Aug;32(4):745-51
references.pmid: 21494810
references.citation: Expert Rev Mol Diagn. 2009 Apr;9(3):231-41
references.pmid: 19379082
references.citation: PLoS One. 2012;7(7):e40817
references.pmid: 22815832
references.citation: Neuroendocrinology. 2007;85(1):54-60
references.pmid: 17310129
references.citation: Br J Cancer. 2008 Oct 21;99(8):1197-203
references.pmid: 18797463