The TLR4 gene polymorphisms and susceptibility to cancer: A systematic review and meta-analysis

Growing studies revealed the association between polymorphisms in Toll-like receptor 4 (TLR4) and susceptibility to cancer, however, the results remained inconsistent. To assess the effect of six selected SNPs (rs1927914, rs4986790, rs4986791, rs11536889, rs1927911 and rs2149356) in TLR4 on cancer, we conducted a meta-analysis, up to February 2012, 22 case-control studies were available. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for polymorphisms in TLR4 and cancer risk were estimated. 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). Moreover, in terms of stratified analyses by cancer type for SNP rs4986790, significantly elevated risk was observed to be associated with G allele in gastric cancer and 'other cancers'. These findings indicate that polymorphisms in TLR4 may play a role, although modest, in cancer development.