Institute of Stomatology, Nanjing Medical University, Nanjing, China ; Section of Clinical Epidemiology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China.
Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China.
PLoS One. 2013 Dec 20;8(12):e82858. doi: 10.1371/journal.pone.0082858. eCollection 2013.
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.
Toll 样受体（TLRs）的激活可能是肿瘤细胞免疫逃避的一个重要事件。最近，许多研究已经调查了 TLR2-196 到-174del 及 TLR4 的两个单核苷酸多态性（rs4986790 和 rs4986791）与不同类型癌症易感性之间的关系；然而，结果仍然存在争议。本研究的目的是通过纳入已发表的研究进行荟萃分析，评估 TLR2 和 TLR4 多态性与癌症风险之间的关系。
方法/主要发现：从 34 篇文献中纳入了一个由 14627 例病例和 17438 例对照组成的数据集，用于评估总体癌症风险或癌症特异性风险与 TLRs 三个单核苷酸多态性（TLR2-196 到-174del、TLR4 rs4986790 和 rs4986791）之间的关系。结果表明，这三种多态性均与癌症风险增加显著相关（显性模型：TLR2-196 到-174del 的 OR=1.64，95%CI：1.04-2.60；TLR4 rs4986790 的 OR=1.19，95%CI：1.01-1.41；TLR4 rs4986791 的 OR=1.47，95%CI：1.120-1.80）。分层分析发现，TLR2-196 到-174del 对癌症风险的影响在白种人和南亚人群亚组中仍然显著，但在东亚人群中不显著。然而，rs4986791 与癌症风险的关联在南亚人和东亚人群中均显著，但在白种人群中不显著。此外，rs4986790 与消化系统癌症（显性模型：OR=1.76，95%CI：1.13-2.73）和女性特有的癌症（显性模型：OR=1.50，95%CI：1.16-1.94）的风险之间存在统计学关联。然而，TLR2-196 到-174del 和 TLR4 rs4986791 与消化系统癌症风险之间没有显著关联。
结论/意义：本荟萃分析提供了 TLR2 和 TLR4 多态性与癌症风险之间关联的额外证据。需要进一步进行设计良好、样本量大的研究来证实这一结论。
