Association of TLR2 and TLR4 polymorphisms with risk of cancer: a meta-analysis

PLoS One. 2013 Dec 20;8(12):e82858. doi: 10.1371/journal.pone.0082858. eCollection 2013.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Digestive System Neoplasms / ethnology
  • Digestive System Neoplasms / genetics*
  • Digestive System Neoplasms / immunology
  • Digestive System Neoplasms / pathology
  • Female
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / ethnology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology
  • Risk
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 4 / immunology
  • White People

Substances

  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4

Grants and funding

This work was supported in part by National Natural Science Foundation of China (81270044 and 81302361), Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Natural Science Foundation (BK2011764) and Jiangsu Province Clinical Science and Technology Projects (BL2012008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.