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Association of TLR2 and TLR4 Polymorphisms with Risk of Cancer: A Meta-Analysis

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  • Longbiao Zhu
  • Hua Yuan
  • Tao Jiang
  • Ruixia Wang
  • Hongxia Ma
  • Shuangyue Zhang

Abstract

Backgrounds: The activation of Toll-like receptors (TLRs) may be an important event in the immune evasion of tumor cell. Recently, numerous studies have investigated the associations between TLR2 −196 to −174 del and two SNPs of TLR4 (rs4986790 and rs4986791) and the susceptibility to different types of cancer; however, the results remain conflicting. The aim of this study was to assess the association between TLR2 and TLR4 polymorphisms and cancer risk in a meta-analysis with eligible published studies. Methodology/Principle Findings: A dataset composed of 14627 cases and 17438 controls from 34 publications were included in a meta-analysis to evaluate the association between overall cancer risk or cancer-specific risk and three SNPs of TLRs (TLR2 −196 to −174 del, TLR4 rs4986790 and rs4986791). The results showed that all of these three polymorphisms were significantly associated with the increased cancer risk (dominant model: OR = 1.64, 95% CI: 1.04–2.60 for TLR2 −196 to −174 del; OR = 1.19, 95% CI: 1.01–1.41 for TLR4 rs4986790; and OR = 1.47, 95% CI: 1.120–1.80 for TLR4 rs4986791; respectively). In stratified analysis, we found the effect of TLR2 −196 to −174 del on cancer risk remained significant in the subgroup of Caucasians and South Asians, but not in East Asians. However, the association between rs4986791 and cancer risk was significant in both South Asians and East Asians, but not in Caucasians. Furthermore, the association between rs4986790 and cancer risk was statistically significant in digestive cancers (dominant model: OR = 1.76, 95% CI: 1.13–2.73) and female-specific cancers (dominant model: OR = 1.50, 95% CI: 1.16–1.94). However, no significant association with risk of digestive system cancers was observed for TLR2 −196 to −174 del and TLR4 rs4986791. Conclusions/Significance: This meta-analysis presented additional evidence for the association between TLR2 and TLR4 polymorphisms and cancer risk. Further well-designed investigations with large sample sizes are required to confirm this conclusion.

Suggested Citation

  • 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.
    • Handle: RePEc:plo:pone00:0082858
    DOI: 10.1371/journal.pone.0082858
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    References listed on IDEAS

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    1. Alan Aderem & Richard J. Ulevitch, 2000. "Toll-like receptors in the induction of the innate immune response," Nature, Nature, vol. 406(6797), pages 782-787, August.
    2. 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.
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    1. Pei-Hsuan Weng & Yi-Ling Huang & John H Page & Jen-Hau Chen & Jianfeng Xu & Stella Koutros & Sonja Berndt & Stephen Chanock & Meredith Yeager & John S Witte & Rosalind A Eeles & Douglas F Easton & Dav, 2014. "Polymorphisms of an Innate Immune Gene, Toll-Like Receptor 4, and Aggressive Prostate Cancer Risk: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(10), pages 1-12, October.

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