Abstract
BackgroundToll-like receptor 4 (TLR4) is a receptor of lipopolysaccharide in the signaling transduction of gastric epithelial cell. It plays a pivotal role in activation of innate immunity and pathogen recognition and thus acts as a modulator in the development and progression of gastric cancer. Growing studies explored the association of polymorphisms in TLR4 with susceptibility to gastric cancer, but the results have remained controversial and conflicting. To investigate the effect of two selected TLR4 (+896A/G and +1196C/T) polymorphisms on gastric cancer, we performed a meta-analysis.MethodsA comprehensive search was conducted to identify all eligible case-control publications investigating the association between TLR4 polymorphisms and gastric cancer risk. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were used to assess such association.ResultsUp to March 26 2014, 10 published case-control studies from PubMed and EMBase were available, involving a total of 1888 gastric cancer patients and 3433 control subjects. In the overall meta-analyses, a significantly increased gastric cancer risk was detected in TLR4 +896A/G polymorphism (heterozygous model, AG vs. AA: OR = 1.67, 95% CI, 1.39–2.01; additive model, G vs. A: OR = 1.64, 95% CI, 1.37–1.95) and TLR4 +1196C/T polymorphism (heterozygous model, CT vs. CC: OR = 1.42, 95% CI, 1.11–1.81; additive model, T vs. C: OR = 1.36, 95% CI, 1.08–1.72), similar results were obtained in the subgroup analyses of Caucasian, whereas no associations were detected in any genetic models of non-Caucasian.ConclusionsThe overall results suggest that TLR4 polymorphisms (+896A/G and +1196C/T) may be associated with a significantly increased gastric cancer risk in Caucasian.
Highlights
Gastric cancer is one of the most common malignancy and the third leading cause of cancer death worldwide, with an estimated 952,000 new cases and 723,000 deaths occurred in 2012 [1]
The identified studies in our meta-analysis met the following criteria: (1) studies investigating the association of Toll-like receptor 4 (TLR4) polymorphisms (+896A/G or +1196C/T) with gastric cancer risk; (2) case-control studies and studies included available genotype frequencies; (3) inclusion of comprehensive data to calculate odds ratio (OR) and 95% confidence interval (CI); (4) publications with full-text article
According to the inclusion and exclusion criteria, 10 case-control studies that consisted of a total of 1888 gastric cancer patients and 3433 control subjects were included in this meta-analysis [11,16,23,24,25,26,27,28,29,30]
Summary
Gastric cancer is one of the most common malignancy and the third leading cause of cancer death worldwide, with an estimated 952,000 new cases and 723,000 deaths occurred in 2012 [1]. Chronic inflammation is well known to play a critical role in initiating and promoting several human cancers including gastric cancer. TLRs activation contributes significantly to the initiation and maintenance of inflammatory response, dysregulation of TLRs signaling may lead to an imbalance state between proinflammatory and anti-inflammatory cytokines, and to an increased susceptibility to chronic inflammatory diseases and cancer [4]. Human TLR4 gene is located on chromosome 9q32-q33 and contains four exons. Toll-like receptor 4 (TLR4) is a receptor of lipopolysaccharide in the signaling transduction of gastric epithelial cell. It plays a pivotal role in activation of innate immunity and pathogen recognition and acts as a modulator in the development and progression of gastric cancer. To investigate the effect of two selected TLR4 (+896A/G and +1196C/T) polymorphisms on gastric cancer, we performed a meta-analysis
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