Abstract
ObjectiveGenetic polymorphisms of Toll-like receptors (TLRs) may influence the effects of H. pylori infection and play important roles in gastric carcinogenesis. The aim of this study was to determine whether the polymorphisms of TLR4 and TLR9 are associated with susceptibility to gastric carcinoma and its prognosis.MethodsThis study consisted of 314 patients with gastric cancer and 314 healthy controls. The polymorphisms were assessed using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis. Survival was analyzed by Kaplan–Meier survival curves.ResultsNo variant genotypes of TLR4+896A/G, TLR4+1196C/T, or TLR9 -1237T/C were detected. For TLR9 -1486 T/C, multiple logistic regression analyses revealed that compared with the TT homozygote, patients with both the TC variant (adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.04–2.10) and the CC variant (adjusted OR = 1.63, 95% CI = 1.01–2.64) had higher risks of gastric cancer. Further stratification analyses revealed that an increased risk of gastric cancer associated with C carriers was evident among females (adjusted OR = 1.84, 95%CI = 1.02–3.33), in younger subjects aged less than 60 years old (adjusted OR = 1.86, 95%CI = 1.15–3.00), and subjects with H. pylori infection (adjusted OR = 1.53, 95% CI = 1.03–2.27). We also observed a significant association between C carriers and noncardia gastric cancer (adjusted OR = 1.51, 95% CI = 1.03–2.20). In addition, we demonstrated that the C carrier genotype and H. pylori infection may have a synergistic effect and conferred an OR of 2.44 for developing gastric cancer. TLR9 -1486C was also identified as an independent marker of poor survival of carcinoma.ConclusionsOur results suggest that TLR9 -1486C carriers are associated with an increased risk and poor prognosis of gastric carcinoma in the Chinese population.
Highlights
Helicobacter pylori is a major cause of gastric cancer [1]
The host immune response has a strong role in defining the outcome of H. pylori infection, and polymorphisms in genes that control this immune response have been shown to influence the risk of gastric cancer[4,5,6]
TLR4 and TLR9 are known to be expressed by gastric epithelial cells in the human stomach[12,13], which play an important role in innate immune signaling to H. pylori[14,15,16]
Summary
Helicobacter pylori is a major cause of gastric cancer [1]. only a small percentage of H. pylori-infected patients develop gastric cancer. Toll-like receptors (TLRs) are important innate immunity regulators that can be activated upon recognition of bacterial and viral ligands, known as pathogenassociated molecular patterns (PAMPs)[7,8], and provide the first line of host defense against several conditions including H. pylori infection [9]. TLR4 and TLR9 are known to be expressed by gastric epithelial cells in the human stomach[12,13], which play an important role in innate immune signaling to H. pylori[14,15,16]. Some studies have reported controversial findings surrounding the role of TLR4 in activation of the innate immune response to H. pylori[17,18].
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