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Cancers (Basel). 2019 May 10;11(5). pii: E648. doi: 10.3390/cancers11050648.

Polymorphism in Toll-Like Receptors and Helicobacter Pylori Motility in Autoimmune Atrophic Gastritis and Gastric Cancer.

Author information

1
Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. vdere@cro.it.
2
Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. orepetto@cro.it.
3
Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. mdezorzi@cro.it.
4
Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. mtcasarotto@cro.it.
5
Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. massimo.tedeschi@cro.it.
6
First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy. paolo.giuffrida01@universitadipavia.it.
7
First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy. marco.lenti@unipv.it.
8
Gastroenterologia Oncologica Sperimentale, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. raffaella.magris@cro.it.
9
Preventive Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. gmiolo@cro.it.
10
SSD Endocrinologia e malattie del metabolismo, Azienda per l'Assistenza Sanitaria 5 Friuli Occidentale, 33170 Pordenone, Italy. cinzia.mazzon@aas5.sanita.fvg.it.
11
SSD Endocrinologia e malattie del metabolismo, Azienda per l'Assistenza Sanitaria 5 Friuli Occidentale, 33170 Pordenone, Italy. giorgio.zanette@aas5.sanita.fvg.it.
12
Pathology Dept CRO Aviano, IRCCS, National Cancer Institute, 33081 Aviano, Italy. lara.alessandrini@aopd.veneto.it.
13
Department of Medicine (DIMED), Pathology, Azienda Ospedaliera di Padova, 35121 Padova, Italy. lara.alessandrini@aopd.veneto.it.
14
Pathology Dept CRO Aviano, IRCCS, National Cancer Institute, 33081 Aviano, Italy. vcanzonieri@cro.it.
15
Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy. vcanzonieri@cro.it.
16
Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. lcaggiari@cro.it.
17
Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. szanussi@cro.it.
18
Immunopatologia e Biomarcatori Oncologici/Bio-proteomics facility, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. asteffan@cro.it.
19
First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, 27100 Pavia, Italy. a.disabatino@smatteo.pv.it.
20
Gastroenterologia Oncologica Sperimentale, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy. rcannizzaro@cro.it.

Abstract

Autoimmune atrophic gastritis (AAG) is associated with an increased risk of certain types of gastric cancer (GC). Helicobacter pylori (H. pylori) infection may have a role in the induction and/or maintenance of AAG and GC. Toll-like receptors (TLR) are essential for H. pylori recognition and subsequent innate and adaptive immunity responses. This study therefore aimed to characterize TLR polymorphisms, and features of bacterial flagellin A in samples from patients with AAG (n = 67), GC (n = 114) and healthy donors (HD; n = 97). TLR5 rs5744174 C/C genotype was associated with GC, lower IgG anti H. pylori response and a higher H. pylori flagellin A abundance and motility. In a subset of patients with AAG, H. pylori strains showed a reduction of the flagellin A abundance and a moderate motility compared with strains from GC patients, a prerequisite for active colonization of the deeper layers of the mucosa, host immune response and inflammation. TLR9 rs5743836 T allele showed an association with serum gastrin G17. In conclusion, our study suggests that alterations of flaA protein, moderate motility in H. pylori and two polymorphisms in TLR5 and TLR9 may favor the onset of AAG and GC, at least in a subset of patients. These findings corroborate the function of pathogen-host cell interactions and responses, likely influencing the pathogenetic process.

KEYWORDS:

Helicobacter pylori; autoimmune gastritis; flagellin A; toll-like receptor 5 (TLR5); toll-like receptor 9 (TLR9)

PMID:
31083432
DOI:
10.3390/cancers11050648
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