Impact of Toll-like receptor 4 polymorphisms on risk of cancer

Abstract

Toll-like receptor 4 (TLR4) is one of the key immune system effectors playing the main role in recognition of viruses and bacteria. Dysregulation of the TLR4 signaling owing to single nucleotide polymorphisms (SNPs) may alter the ligand binding and balance between pro- and anti-inflammatory cytokines, thereby modulating the risk of chronic inflammation and cancer. TLR4 polymorphisms may be associated with at least nine types of cancer. The most intensively investigating TLR4 polymorphisms are Asp299Gly (rs4986790) and Thr399Ile (rs4986791). It seems to be that Asp299Gly and Thr399Ile are related to increased risk of precancerous gastric lesions, and, possibly, gastric cancer. Thr399Ile also may be connected with gallbladder cancer, and both of these polymorphisms apparently have no impact on risk of prostate cancer. However, the data about many SNPs and their associations with different types of cancer are conflicting, and further large, well-designed, comprehensive studies in various populations are necessary for solution of this problem. The short list of TLR4 SNPs for further investigation may include TLR4_896A/G (Asp299Gly, rs4986790), TLR4_1196C/T (Thr399Ile, rs4986791), Thr135Ala, TLR4_1859 G/A (rs11536858), TLR4_2032T/C (rs10116253), TLR4_2437A/G (rs1927914), TLR4_2856T/C (rs10759932), TLR4_3725 G/C (rs11536889), TLR4_7764 G/A (rs1927911), TLR4_11350G/C, TLR4_11912 G/T (rs2149356), TLR4_16649G/C (rs7873784), and TLR4_17050T/C (rs11536891).