Single nucleotide polymorphism typing of the human toll-like receptor 4 gene at the 2-kb upstream region of the 5' untranslated region: New enclosure strategy for the risk grouping of poorly-differentiated gastric adenocarcinoma patients

Ohara, Tadashi; Kanoh, Yuhsaku; Tani, Norio; Ohdaira, Hironori; Suzuki, Yutaka; Kameyama, J; Yoshino, Katsumi; Kitajima, Masaki

doi:10.3892/mmr_00000055

Cited by 1 publication

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References 16 publications

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“…Recent studies, conducted in several populations, have shown associations between the polymorphisms TLR1 rs5743618 (Ile602Ser) (154), TLR2 −196 to −174del (155–158), TLR2 rs3804099 (157), TLR4 rs4986790 (Asp299Gly) (155, 157, 159), TLR4 rs4986791 (Thr399Ile) (160), TLR4 rs10116253 (161), TLR4 rs10983755 (162), TLR4 rs11536889 (+3725G/C) (155), TLR4 rs1927911 (161), TLR5 rs5744174 (158), TLR9 rs187084 (−1486 T/C) (163), and CD14 rs2569190 (−260 C/T) (155, 164–167), and risk of GC development in an ethnic-specific manner (Table 1). In addition, three polymorphisms located in the TLR4 mRNA promoter region (sites −2081, −2026, and −1601) and TLR4 Thr135Ala at the leucine-rich repeat (LRR), have been associated with poorly differentiated GC (168, 169). …”

Section: Toll-like Receptors and Helicobacter Pylori-related Gastric mentioning

confidence: 99%

Pattern-Recognition Receptors and Gastric Cancer

2014

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Chronic inflammation has been associated with an increased risk of several human malignancies, a classic example being gastric adenocarcinoma (GC). Development of GC is known to result from infection of the gastric mucosa by Helicobacter pylori, which initially induces acute inflammation and, in a subset of patients, progresses over time to chronic inflammation, gastric atrophy, intestinal metaplasia, dysplasia, and finally intestinal-type GC. Germ-line encoded receptors known as pattern-recognition receptors (PRRs) are critical for generating mature pro-inflammatory cytokines that are crucial for both Th1 and Th2 responses. Given that H. pylori is initially targeted by PRRs, it is conceivable that dysfunction within genes of this arm of the immune system could modulate the host response against H. pylori infection, and subsequently influence the emergence of GC. Current evidence suggests that Toll-like receptors (TLRs) (TLR2, TLR3, TLR4, TLR5, and TLR9), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) (NOD1, NOD2, and NLRP3), a C-type lectin receptor (DC-SIGN), and retinoic acid-inducible gene (RIG)-I-like receptors (RIG-I and MDA-5), are involved in both the recognition of H. pylori and gastric carcinogenesis. In addition, polymorphisms in genes involved in the TLR (TLR1, TLR2, TLR4, TLR5, TLR9, and CD14) and NLR (NOD1, NOD2, NLRP3, NLRP12, NLRX1, CASP1, ASC, and CARD8) signaling pathways have been shown to modulate the risk of H. pylori infection, gastric precancerous lesions, and/or GC. Further, the modulation of PRRs has been suggested to suppress H. pylori-induced inflammation and enhance GC cell apoptosis, highlighting their potential relevance in GC therapeutics. In this review, we present current advances in our understanding of the role of the TLR and NLR signaling pathways in the pathogenesis of GC, address the involvement of other recently identified PRRs in GC, and discuss the potential implications of PRRs in GC immunotherapy.

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