Many epidemiological studies have shown the association between certain genetic variations in the Toll-like receptor 4 (TLR4) gene (for example, rs4986790 and rs4986791) and cancer risk.
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).
Our meta-analysis identified that two SNPs (rs4986790 and rs4986791) in TLR4 were associated with increased cancer risk (for rs4986790: OR=1.24, 95% CI=1.01-1.52 in dominant model; OR=1.24, 95% CI=1.02-1.52 in overdominant model; for rs4986791: OR=1.81, 95% CI=1.18-2.77 in allele comparison; OR=1.79, 95% CI=1.15-2.80 in dominant model; OR=1.70, 95% CI=1.09-2.67 in overdominant model) and one SNP (rs1927911) in TLR4 was associated with decreased cancer risk (for rs1927911: OR=0.63, 95% CI=0.41-0.99 in allele comparison; OR=0.57, 95% CI=0.35-0.95 in dominant model; OR=0.67, 95% CI=0.46-0.97 in codominant model).
Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms.
Human colon adenocarcinomas from patients with TLR4-D299G were more frequently of an advanced stage (International Union Against Cancer [UICC] ≥III, 70% vs 46%; P = .0142) with metastasis (UICC IV, 42% vs 19%; P = .0065) than those with wild-type TLR4.
In a prospective cohort study, we examined 62 patients undergoing major surgical cancer therapy for Toll-like receptor 4 (TLR4) gene polymorphisms (Asp299Gly and Thr399Ile) and their influence on cytokine levels pre- and postoperatively, as well as cytokine levels after whole blood lipopolysaccharide (LPS) stimulation.