title: Genetic polymorphisms in the Toll-like receptor signalling pathway in Helicobacter pylori infection and related gastric cancer.
abstract: BACKGROUND
  Gastric cancer (GC) is a progressive process initiated by Helicobacter pylori-induced inflammation. Initial recognition of H. pylori involves Toll-like receptors (TLRs), central molecules in the host inflammatory response. Here, we investigated the association between novel polymorphisms in genes involved in the TLR signalling pathway, including TLR2, TLR4, LBP, MD-2, CD14 and TIRAP, and risk of H. pylori infection and related GC.
  
  
  METHODS
  A case-control study comprising 310 ethnic Chinese individuals (87 non-cardia GC cases and 223 controls with functional dyspepsia) was conducted. Twenty-five polymorphisms were detected by MALDI-TOF mass spectrometry, PCR, PCR-RFLP and real-time PCR.
  
  
  RESULTS
  Seven polymorphisms showed significant associations with GC (TLR4 rs11536889, TLR4 rs10759931, TLR4 rs1927911, TLR4 rs10116253, TLR4 rs10759932, TLR4 rs2149356 and CD14 -260 C/T). In multivariate analyses, TLR4 rs11536889 remained a risk factor for GC (OR: 3.58, 95% CI: 1.20-10.65). TLR4 rs10759932 decreased the risk of H. pylori infection (OR: 0.59, 95% CI: 0.41-0.86). Statistical analyses assessing the joint effect of H. pylori infection and the selected polymorphisms revealed strong associations with GC (TLR2, TLR4, MD-2, LBP and TIRAP polymorphisms).
  
  
  CONCLUSIONS
  Novel polymorphisms in TLR2, TLR4, MD-2, LBP, CD14 and TIRAP, genes encoding important molecules of the TLR signalling pathway, showed clear associations with H. pylori-related GC in Chinese.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Castaño-Rodríguez
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Nadeem O
authors.initials: NO
authors.lastname: Kaakoush
authors.affiliation: School of Statistics, National University of Colombia, Medellin, Colombia.
authors.forename: Aryce L
authors.initials: AL
authors.lastname: Pardo
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Khean-Lee
authors.initials: KL
authors.lastname: Goh
authors.affiliation: Division of Gastroenterology, Department of Medicine, Changi General Hospital, Singapore, Singapore.
authors.forename: Kwong Ming
authors.initials: KM
authors.lastname: Fock
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia. Electronic address: h.mitchell@unsw.edu.au.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Mitchell
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000276:immunology; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D002681:China; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000099231:Lipopolysaccharide-Binding Protein; C495377:LY96 protein, human; C434984:TIRAP protein, human; C495342:TLR2 protein, human; C495345:TLR4 protein, human
keywords: Helicobacter pylori; Polymorphism; Stomach neoplasms; Toll-like receptors