Genetic variations of TLR5 gene interacted with Helicobacter pylori infection among carcinogenesis of gastric cancer

Abstract

Gastric cancer (GC) ranks the second prevalent cancer type and the second cancer-related death in China. However, the precise mechanisms of GC development remain poorly understood. Chronic infection with Helicobacter pylori is the strongest identified risk factor for GC. Toll-like receptor (TLR) genes, which play critical roles in Helicobacter pylori induced chronic inflammation, may also be implicated in GC susceptibility. TLR5 signaling deficiency could deregulate a cascade of inflammatory events. In current study, we systematically evaluated genetic variations of TLR5, and their interaction with Helicobacter pylori infection among carcinogenesis of gastric cancer, using a large case-controls study among Chinese population. Minor alleles of three SNPS, including rs5744174 (P = 0.001), rs1640827 (P = 0.005), and rs17163737 (P = 0.004), were significantly associated with increased GC risk (OR ranged from 1.20–1.24). Significant interactions with Helicobacter pylori infection were also identified for rs1640827 (P for interaction = 0.009) and rs17163737 (P for interaction = 0.006). These findings suggest that genetic variants in TLR5 may modify the role of Helicobacter pylori infection in the process of causing GC.

TLR5 is a new reporter for triple‐negative breast cancer indicated by radioimmunoimaging and fluorescent staining

“…For breast cancer molecular imaging, there were some reports about target molecules with labelled radioisotope, for example 18 F-labelled aptamers of human epidermal growth factor receptor 2 (Her2/ErbB2), 21 125 I/ 131 I-labelled anti ICAM-1 22 ( intercellular cell adhesion molecule-1) and 89 Zr-Transferrin. 23 However, these target molecules still exist some deficiency, such as low selection and low molecular expression on tumour.…”

“…Nuclear medicine molecular imaging is a kind of non-invasive whole-body scanning modality based on metabolism and function abnormal, more suitable for the detection and quantification of tumour target molecular, compared with traditional imaging CT (computed tomography) and MRI (magnetic resonance imaging) in diagnosis and tumour staging. 6 Nowadays, 18 F-FDG (F-18-deoxyglucose) PET/CT (positron emission tomography/computed tomography) was widely used in clinic for evaluation tumour metabolisms. 7 However, 18 F-FDG is a non-specific agent, which made diagnosis sometimes not accurate.…”

“…6 Nowadays, 18 F-FDG (F-18-deoxyglucose) PET/CT (positron emission tomography/computed tomography) was widely used in clinic for evaluation tumour metabolisms. 7 However, 18 F-FDG is a non-specific agent, which made diagnosis sometimes not accurate. Searching the better molecular target for tumour diagnosis and therapy is critical for clinic.…”

“…[12][13][14][15] As a member of TLRs, TLR5 is known to specifically recognize flagellin, which is the only protein ligand in TLR family. 16 Recently, TLR5 was found highly expressed on a variety of cancer, such as ovarian cancer, 17 gastric cancer 18 and colon cancer, 19 and tumours' growth was significantly inhibited by bacterial flagellin activation through TLR5 pathway. 21 More importantly, TLR5 was found highly expressed in both TNBC and non-TNBC, 20 tightly related to cancer progression, while TLR5 expressed on immunocytes or tumour cells within breast cancer existed controversies.…”

Dysbiosis Promotes Gastric Diseases and Impede Therapies by Hijacking Gut Immune Homeostasis

“…Besides altering regulatory pathways, numerous studies proposed that host genetic makeup can influence the interaction of various microbiota with host cells. For instance, genetic variants rs1640827 and rs17163737 of TLR5 lead to enhanced interactions with H.pylori therefore increasing gastric cancer susceptibility[30]. A similar mechanism during dysbiosis is anticipated to lead to the similar response in various diseases.…”