Helicobacter pylori infection and gastric carcinoma： Not allthe strains and patients are alike

• 作者: Natale Figura, Luigi Marano, Elena Moretti, Antonio Ponzetto
• 来源期刊: 世界胃肠肿瘤学杂志：英文版（电子版）
• 学科: 医学
• 关键词: HELICOBACTER PYLORI infection CAGA CagAgene polymorphism HAPLOTYPE Human gene mutation Genemethylation Gastriccarcinoma Inflammatorycytokine
• 年，卷（期）: 2016,（1）
• 页码范围: 40-54
• 页数: 15页
• 分类号: R

摘要

Gastric carcinoma （GC） develops in only 1%-3% ofHelicobacter pylori （H. pylori ） infected people. Therole in GC formation of the bacterial genotypes, genepolymorphisms and host＇s factors may therefore beimportant. The risk of GC is enhanced when individualsare infected by strains expressing the oncoprotein CagA,in particular if CagA has a high number of repeatscontaining the EPIYA sequence in its C＇-terminal variableregion or particular amino acid sequences flank theEPIYA motifs. H. pylori infection triggers an inflammatoryresponse characterised by an increased secretion ofsome chemokines by immunocytes and colonisedgastric epithelial cells; these molecules are especiallyconstituted by proteins composing the interleukin-1beta （IL-1β） group and tumour necrosis factor-alpha（TNF-α）. Polymorphisms in the promoter regions ofgenes encoding these molecules, could account for highconcentrations of IL-1β and TNF-α in the gastric mucosa,which may cause hypochlorhydria and eventually GC.Inconsistent results have been attained with otherhaplotypes of inflammatory and anti-inflammatorycytokines. Genomic mechanisms of GC development aremainly based on chromosomal or microsatellite instability（MSI） and deregulation of signalling transductionpathways. H. pylori infection may induce DNA instabilityand breaks of double-strand DNA in gastric mucocytes.Different H. pylori strains seem to differently increasethe risk of cancer development run by the host. CertainH. pylori genotypes （such as the cagA positive） inducehigh degrees of chronic inflammation and determinean increase of mutagenesis rate, oxidative-stress,mismatch repair mechanisms, down-regulation of baseexcision and genetic instability, as well as generationof reactive oxygen species that modulate apoptosis;these phenomena may end to trigger or concur to GCdevelopment.