title: The role of TLR2, TLR4 and CD14 genetic polymorphisms in gastric carcinogenesis: a case-control study and meta-analysis.
abstract: BACKGROUND
  In addition to Helicobacter pylori infection, host genetic factors contribute to gastric cancer (GC). Recognition of H. pylori is known to involve Toll-like receptors (TLR), which subsequently leads to activation of NF-κB. Thus, the overall aim of this study was to estimate for the first time the pooled effect size of polymorphisms in TLR2, TLR4 and CD14 on GC development through a meta-analysis.
  
  
  METHODS
  A case-control study comprising 284 ethnic Chinese individuals (70 non-cardia GC cases and 214 functional dyspepsia controls) was conducted for the genotyping of TLR2 -196 to -174del, CD14 -260 C/T and TLR4 rs11536889 using PCR, RT-PCR and mass spectrometry. Case-control studies of TLR2, TLR4 and CD14 polymorphisms and GC were searched up to June 2012. Pooled odds ratios and 95% confidence intervals were obtained by means of the random effects model.
  
  
  RESULTS
  In our ethnic Chinese case-control study, the TLR4 rs11536889 C allele increased the risk of GC (OR: 1.89, 95%CI: 1.23-2.92) while the CD14 -260 T allele was protective (OR: 0.62, 95%CI: 0.42-0.91). TLR2 -196 to -174 increased the risk of GC only in H. pylori-infected individuals (OR: 3.10, 95%CI: 1.27-7.60). In the meta-analysis, TLR4 Asp299Gly showed borderline results in the general analysis (pooled OR: 1.58, 95%CI: 0.98-2.60), nevertheless, stratified analysis by ethnicity showed that the mutant allele was a definitive risk factor for GC in Western populations (pooled OR: 1.87, 95%CI: 1.31-2.65). There was a potential association between the TLR2 -196 to -174 deletion allele and GC in Japanese (pooled OR: 1.18, 95%CI: 0.96-1.45). TLR4 Thr399Ile did not provide significant results.
  
  
  CONCLUSIONS
  TLR4 rs11536889 and CD14 -260 C/T are associated with non-cardia GC in Chinese. Based on our meta-analysis, the TLR signalling pathway is involved in gastric carcinogenesis, TLR4 Asp299Gly and TLR2 -196 to -174del showing associations with GC in an ethnic-specific manner.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Castaño-Rodríguez
authors.forename: Nadeem O
authors.initials: NO
authors.lastname: Kaakoush
authors.forename: Khean-Lee
authors.initials: KL
authors.lastname: Goh
authors.forename: Kwong Ming
authors.initials: KM
authors.lastname: Fock
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D016481:Helicobacter Infections / Q000382:microbiology; D016480:Helicobacter pylori; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017594:Publication Bias; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
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