An updated systematic review of the association between the TLR4 polymorphism rs4986790 and cancers risk

Toll-like receptor 4 (TLR4) is a lipopolysaccharide receptor that may influence tumor progression through inflammatory response and immune response. This complex process mainly occurs within cells. The correlation between TLR4 and neoplasms has been of great interest, but discrepancies remain.

We analyze the literature retrieved from five databases (Web of Science, PubMed, Embase, CNKI, and Wan Fang) to assess the intensity of association using odds ratio (ORs) and 95% confidence intervals (95% CI). Meta-regression and subgroup analysis were utilized to find sources of heterogeneity. Publication bias is estimated using contour-enhanced funnel plots, Begg's test, and Egger's test, and we implemented sensitivity analysis to clarify the reliability of the outcomes. We also conducted an evaluation of the sample size using trial sequential analysis (TSA) method.

We found a significant association between rs4986790 and tumors (dominant model: OR [95% CI] = 1.25 [1.11-1.42]; heterozygous model OR [95% CI] = 1.25 [1.11-1.41]; and additive model: OR [95% CI] = 1.25 [1.10-1.41]. Specifically, the rs4986790 minor allele G may increase the risk of gastric cancer (dominant model: OR [95% CI] = 1.62 [1.3-2.03]; heterozygous model: OR [95% CI] = 1.57 [1.24-1.97]; additive model: OR [95% CI] = 1.64 [1.31-2.05] and other tumors (dominant model: OR [95% CI] = 1.36 [1.17-1.57]; heterozygous model: OR [95% CI] = 1.43 [1.25-1.63]; additive model: OR [95% CI] = 1.35 [1.18-1.55]. Further subgroup analysis showed that this association are both present in Caucasian and Asian.

The outcomes of our systemic review proved that the TLR4 polymorphism rs4986790 is associated with cancer, especially with gastric cancer, and this strong correlation are evident in Caucasians and Asian.