Cytokine and chemokine modification by Toll‐like receptor polymorphisms is associated with nasopharyngeal carcinoma

Abstract

Toll-like receptors (TLR) play a pivotal role in sensing a wide range of pathogens, including bacteria, fungi and viruses. A dysregulation of TLR signaling may increase the risk of developing chronic inflammatory diseases and cancers. The aim of this study was to investigate the association of TLR2 R753Q, TLR4 D299G, and T399I polymorphisms with nasopharyngeal carcinoma (NPC) and to explore the effects of these polymorphisms on cytokine and chemokine expression in NPC biopsies. The genotypes of the three loci among 236 patients with NPC and 287 healthy controls were determined by PCR-RFLP. Cytokines and chemokines mRNA and protein in NPC biopsies were measured by real-time quantitative PCR and ELISA, respectively. Results showed that the combined CT/TT genotype of T399I was associated with increased NPC risk, with an odds ratio of 1.853 (95% confidence interval: 1.184-2.961). Also, individuals with the T allele of T399I showed a 1.842-fold increase in NPC risk compared to those with the T399I C allele (95% confidence interval: 1.213-3.015). Messenger RNA levels of interleukin (IL)-1a, tumor necrosis factor-a and IL-10 were significantly elevated in patients with T399I combined CT/ TT genotype; IL-1a and IL-10 protein concentration significantly increased in NPC patients with T399I combined CT/TT genotype compared to those with the T399I CC genotype. Our data suggest that TLR4 T399I modify cytokines and chemokines patterns and play a role in the development of NPC. (Cancer Sci 2012; 103: 653-658)

Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival

“…It has been reported that TLRs genes are expressed on endothelial, epithelial cells and tumour cells, including head and neck cancer cells (Huang et al, 2005;Szczepanski et al, 2009;Bergmann et al, 2011;Chuang et al, 2012;Theodoropoulos et al, 2012). Dysregulation in TLRs signalling has previously been associated with a higher risk of developing different types of cancers, including prostate, cervical and nasopharyngeal carcinoma (Pandey et al, 2009;Yang et al, 2012). TLR3 gene is expressed in different malignant cells, such as breast cancer and melanoma (Chuang et al, 2012).…”

Potential Association Between TLR4 and Chitinase 3-Like 1 (CHI3L1/YKL-40) Signaling on Colonic Epithelial Cells in Inflammatory Bowel Disease and Colitis-Associated Cancer

“…Recent reports have shown that the T399I mutation in TLR4 enhances the expression of TNFα message, which is associated with the risk of nasopharyngeal carcinoma development 112 . This represents a potentially more direct link between the T399I mutation in TLR4 and excessive CHI3L1 expression in nasopharyngeal epithelial cells via TNFα.…”

TLR2,TLR3,TLR4 and CD14 gene polymorphisms associated with oral lichen planus risk

“…Two missense (non‐synonymous) mutations have been identified in the TLR4 gene: replacement of aspartic acid with glycine at amino acid 299 (rs4986790) and replacement of threonine with isoleucine at amino acid 399 (rs4986791). Previous findings have reported that these polymorphisms affect the expression of inflammatory cytokines and chemokines and are associated with the progression of head and neck cancer . In the current study, no associations between these polymorphisms in the TLR4 gene and OLP occurrence were observed.…”