[Show abstract][Hide abstract] 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)-1α, tumor necrosis factor-α and IL-10 were significantly elevated in patients with T399I combined CT/TT genotype; IL-1α 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 Science 02/2012; 103(4):653-8. DOI:10.1111/j.1349-7006.2012.02210.x · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The normal function of excision repair cross complementing group 1 (ERCC1) is essential for maintaining genomic integrity and preventing cellular neoplastic transformation, and multiple studies have reported an association between ERCC1 polymorphisms and increased risk of cancers. To test whether the genetic variants of ERCC1 gene modify the risk of nasopharyngeal carcinoma (NPC), we compared the 8092 C > A and 19007 C > T single nucleotide polymorphisms (SNPs) and the haplotypes of ERCC1 between 267 patients with NPC and 304 healthy controls. Linkage disequilibrium was observed between the two SNPs loci (D' = 0.861). Significant differences of allele frequencies were found for ERCC1 8092C > A between the cases and controls. Individuals with 8092 C allele showed 1.411-fold (OR = 1.411, 95% CI, 1.076-1.850, P = 0.014) increased risk of developing NPC, and the CC haplotype was associated with a significantly increased risk of NPC (OR = 1.712; 95% CI, 1.211-2.421; P = 0.013). No interactions were found between 8092C > A polymorphism and genders, smoking status and alcohol consumption. These results suggested that the polymorphism of ERCC1 8092 C > A might be a contributing factor in the development of NPC in Chinese population.