Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences.

Abstract

Helicobacter pylori infection is associated with the development of a chronic inflammatory response, which may induce peptic ulcers, gastric cancer (GC), and mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic H. pylori infection promotes the genetic instability of gastric epithelial cells and interferes with the DNA repair systems in host cells. Colonization of the stomach with H. pylori is an important cause of non-cardia GC and gastric MALT lymphoma. The reduction of GC development in patients who underwent anti-H. pylori eradication schemes has also been well described. Individual susceptibility to GC development depends on the host's genetic predisposition, H. pylori virulence factors, environmental conditions, and geographical determinants. Biological determinants are urgently sought to predict the clinical course of infection in individuals with confirmed H. pylori infection. Possible candidates for such biomarkers include genetic aberrations such as single-nucleotide polymorphisms (SNPs) found in various cytokines/growth factors (e.g., IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-17A/B, IFN-γ, TNF, TGF-β) and their receptors (IL-RN, TGFR), innate immunity receptors (TLR2, TLR4, CD14, NOD1, NOD2), enzymes involved in signal transduction cascades (PLCE1, PKLR, PRKAA1) as well as glycoproteins (MUC1, PSCA), and DNA repair enzymes (ERCC2, XRCC1, XRCC3). Bacterial determinants related to GC development include infection with CagA-positive (particularly with a high number of EPIYA-C phosphorylation motifs) and VacA-positive isolates (in particular s1/m1 allele strains). The combined genotyping of bacterial and host determinants suggests that the accumulation of polymorphisms favoring host and bacterial features increases the risk for precancerous and cancerous lesions in patients.

• Authors: Karolina Rudnicka, Steffen Backert, Magdalena Chmiela
• Journal: Current topics in microbiology and immunology (Curr Top Microbiol Immunol) Vol. 421 Pg. 53-76 ( 2019) ISSN: 0070-217X [Print] Germany
• PMID: 31123885 (Publication Type: Journal Article, Review)

Chemical References

• Inflammation Mediators
• Virulence Factors

Topics

• Genetic Predisposition to Disease
• Helicobacter Infections (genetics, immunology, microbiology, pathology)
• Helicobacter pylori (genetics, immunology, pathogenicity)
• Humans
• Inflammation Mediators
• Polymorphism, Single Nucleotide
• Stomach Neoplasms (genetics, immunology, microbiology, pathology)
• Virulence Factors