Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in gastric cancer of intestinal and diffuse histotypes

Abstract

SummaryIn the present study we investigated the potential role of Toll-like receptor 4 (TLR-4) Asp299Gly and Thr399Ile polymorphisms as risk factors in the development of gastric cancer. TLR-4 Asp299Gly and Thr399Ile polymorphisms were investigated in 171 Italian patients with sporadic gastric cancer and in 151 controls. Unconditional regression (odds ratio and 95% confidence intervals) were used to investigate the association of the studied polymorphisms with gastric cancer. TLR-4 Thr399Ile polymorphism is linked with an increased susceptibility to gastric cancer (P = 0·023 and hazard ratio = 3·62). No significant association for TLR-4 Asp299Gly polymorphism was found. In the subgroup of patients with intestinal-type gastric cancer, a significant risk of gastric cancer was associated with TLR-4 Thr399Ile genotype (P = 0·006). Our results demonstrated that TLR-4 Thr399Ile polymorphism is linked with an increased susceptibility to gastric cancer. An increased risk for intestinal gastric cancer in carriers of the TLR4 Thr399Ile allele was observed. Future epidemiological studies should consider the possible interactions between proinflammatory genotypes (such as TLR and interleukin-1R polymorphisms) and other risk factors for cancer such as dietary habits and/or exposure to environmental carcinogens.

Flagellin promotes the proliferation of gastric cancer cells via the Toll-like receptor 5

“…Helicobacter pylori infection is the best-known risk factor for gastric adenocarcinoma, and etiological studies have revealed that the attributable risk for gastric cancers conferred by H. pylori is approximately 75% (19). There is evidence supporting the relation between TLR4 polymorphism and the risk of gastric cancers (20,21). It has also been reported that H. pylori augments the growth of gastric cancers via TLR2 or TLR4 pathways (22,23).…”

Characterization of gene polymorphisms related to immune system physiology in Mangalarga horses

“…In this respect, although the Mangalarga horse population studied is in equilibrium for the TLR4 locus, the fact that the population genetic parameters obtained were close to significance does not definitively rule out some potential application of this marker in association studies with important traits in this breed. Alterations in TLR signaling have been associated with the occurrence of different diseases in humans and SNPs identified in the TLR gene family are associated with these conditions (Santini et al, 2008). Moura et al (2008) reported an association between the A896G SNP of the human TLR4 gene and Helicobacter pylori infection, and Santini et al (2008) associated the T1196C polymorphism of the same gene with the development of gastric cancer.…”

“…Alterations in TLR signaling have been associated with the occurrence of different diseases in humans and SNPs identified in the TLR gene family are associated with these conditions (Santini et al, 2008). Moura et al (2008) reported an association between the A896G SNP of the human TLR4 gene and Helicobacter pylori infection, and Santini et al (2008) associated the T1196C polymorphism of the same gene with the development of gastric cancer. In horses, the AY_005808:c.1530A>G polymorphism of the TLR4 gene might play an important physiological role since it causes the substitution of methionine with valine in the protein sequence encoded by exon 3 of the gene (Vychodilova-Krenkova et al 2005).…”

Biomarkers ofHelicobacter pylori-associated gastric cancer

“…104 The risk for gastric mucosal atrophy is also increased substantially by the G796A mutation in NOD1, a cytosolic pattern recognition receptor that responds to peptidoglycan delivered by the H. pylori cag PAI. 105 Polymorphisms in cytokine genes that drive the inflammatory response to H. pylori infection may also influence susceptibility to gastric cancer.…”