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The Role of TLR2, TLR4 and CD14 Genetic Polymorphisms in Gastric Carcinogenesis: A Case-Control Study and Meta-Analysis

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  • Natalia Castaño-Rodríguez
  • Nadeem O Kaakoush
  • Khean-Lee Goh
  • Kwong Ming Fock
  • Hazel M Mitchell

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.

Suggested Citation

  • Natalia Castaño-Rodríguez & Nadeem O Kaakoush & Khean-Lee Goh & Kwong Ming Fock & Hazel M Mitchell, 2013. "The Role of TLR2, TLR4 and CD14 Genetic Polymorphisms in Gastric Carcinogenesis: A Case-Control Study and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(4), pages 1-12, April.
    • Handle: RePEc:plo:pone00:0060327
    DOI: 10.1371/journal.pone.0060327
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    Cited by:

    1. Longbiao Zhu & Hua Yuan & Tao Jiang & Ruixia Wang & Hongxia Ma & Shuangyue Zhang, 2013. "Association of TLR2 and TLR4 Polymorphisms with Risk of Cancer: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-9, December.
    2. Jun Wang & Xufeng Guo & Shijie Yu & Jia Song & Jixiang Zhang & Zhuo Cao & Jing Wang & Min Liu & Weiguo Dong, 2014. "Association between CD14 Gene Polymorphisms and Cancer Risk: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-9, June.

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