Abstract
Previous studies have explored the association between toll-like receptor 4 (TLR4) polymorphisms and risk of various cancers, but the results remained controversial. To obtain an assessment of the effect of TLR4 polymorphisms (rs4986790, rs4986791 and rs11536889) on cancer risk, fifty-five articles (containing 20107 cases and 28244 controls) were recruited for meta-analysis. Our result indicated that two Single Nucleotide Polymorphisms (SNP) in TLR4 were associated with decreased cancer risk for rs4986791: OR = 0.764, 95% CI: 0.652-0.894, P = 0.001 in allele model; OR = 0.769, 95%CI: 0.650-0.909, P = 0.002 in recessive model; OR = 0.505, 95% CI: 0.352-0.726, P = 0.000 in dominant model; for 11536889: OR = 0.927, 95% CI: 0.872–0.984, P = 0.013 in allele model; OR = 0.926, 95% CI: 0.862–0.944,P = 0.034 in recessive model. In terms of subgroup analyses sorted by ethnicity, only polymorphism of rs4986791 had a significant influence on decrease of cancer risk among both Caucasian and Asian populations. The findings suggested that TLR4 polymorphisms may serve as a genetic risk factor for cancers.
Highlights
Toll-like receptors (TLRs) were important innate immune molecules which were used for specific recognition to adjust the adaptive immune response by identifying the pathogen-associated molecular patterns (PAMPs)
Our result indicated that two Single Nucleotide Polymorphisms (SNP) in toll-like receptor 4 (TLR4) were associated with decreased cancer risk for rs4986791: Odd ratio (OR) = 0.764, 95% confidence interval (95% confidence intervals (CI)): 0.652-0.894, P = 0.001 in allele model; OR = 0.769, 95% confidence interval (95%CI): 0.650-0.909, P = 0.002 in recessive model; OR = 0.505, 95% CI: 0.352-0.726, P = 0.000 in dominant model; for 11536889: OR = 0.927, 95% CI: 0.872–0.984, P = 0.013 in allele model; OR = 0.926, 95% CI: 0.862–0.944,P = 0.034 in recessive model
There were 13 kinds of TLRs found in the mammal body, among them, only TLR2 and TLR4 can bond with glycosyl ligand and their intracellular adapters were mainly consist of Toll/IL-1 homologous receptor(TIR), myeloid differentiation factor 88 (My88), TIR domain containing adapter-inducing interferon-β (TRIF), TRIF-related adaptor molecule (TRAM) and MyD88 adaptor-like (MAL)
Summary
Toll-like receptors (TLRs) were important innate immune molecules which were used for specific recognition to adjust the adaptive immune response by identifying the pathogen-associated molecular patterns (PAMPs). TLR4 transmitted the stimulation signals into cell nucleus which was activated by a series of protein cascade reactions [7] Such behavior led to the activation of important immune gene transcription factors such as NF-κB, activator protein-1 and interferon regulatory factor (IRF) that induced the synthesis and release of relevant cell factors like IL-l, IL-2,TNF-α and IFN and enabled the acquired immune action by promoting the maturity of dendritic cells (DC), stimulating a series of immune reactions with different pathogenic microorganism in the end [8]. The MyD88 dependent way mainly mediated the combination of interleukin-1 receptor-associated kinase-1 (IRAK-1), IRAK4 and TLR4, and dissociated www.impactjournals.com/oncotarget
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