<i>Helicobacter pylori</i> vacuolating cytotoxin genotypes and preneoplastic lesions or gastric cancer risk: a meta‐analysis

Abdi, Esmat; Latifi‐Navid, Saeid; Latifi-Navid, Hamid; Safarnejad, Bahareh

doi:10.1111/jgh.13256

Cited by 20 publications

(16 citation statements)

References 45 publications

(64 reference statements)

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“…Fifteen studies in the meta-analysis (1) confirmed the association of the s1m1 genotype with an increased risk for gastric cancer, however studies from Belgian and India only confirmed an association with vacA s1 but not with m1 (8,9). In Thailand (10), s, m or s, m, combination showed no statistically significant association with clinical outcome.…”

Section: Consistencymentioning

confidence: 94%

“…Although there are no value that clearly separates “strong” from “moderate” or “weak” associations, RR values below three are considered moderate or weak (7). The Abdi et al meta-analysis (1) reported relatively weak associations (i.e., RR's below 1.5) for both s1 and m1 and for the combination of s1m1.…”

Section: Strengthmentioning

confidence: 99%

“…Based on the notion that polymorphisms in the H. pylori vacuolating cytotoxin gene might be a determinant of clinical outcome, Abdi et al used meta-analysis to examine the association between vacA gene subtypes and the risk of developing atrophic gastritis, intestinal metaplasia or gastric cancer (1). …”

mentioning

confidence: 99%

“…Abdi et al meta-analysis included 33 studies with 1,446 cases and 2,697 controls and included European, Asian and American populations (1). The authors report that the vacA s1 genotype was associated with the risk of atrophic gastritis, intestinal metaplasia and gastric cancer [i.e., relative risk (RR) =1.116, 95% CI, 1.019–1.222; RR =1.418, 95% CI, 1.035–1.942; and RR =1.333, 95% CI, 1.115–1.593, respectively].…”

mentioning

confidence: 99%

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Helicobacter pylori vacuolating cytotoxin and gastric cancer risk: reconsidered

2016

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Section: Consistencymentioning

confidence: 94%

Section: Strengthmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Helicobacter pylori vacuolating cytotoxin and gastric cancer risk: reconsidered

2016

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“…5,6 The production of vacuolating cytotoxin (VacA), encoded by the vacA gene, is another important virulence factor used by H. pylori to induce cytoplasmic vacuolization in gastric cells. 7,8 Once internalized, VacA induces cytochrome C release from mitochondria, promoting apoptosis. Moreover, VacA binds to the cellular epithelium by interacting with tyrosine phosphatase proteins and enhancing pore formation in cell membranes.…”

mentioning

confidence: 99%

Epigenetic Mechanisms of ATM Activation after Helicobacter pylori Infection

Santos

Gambeloni

Roque

et al. 2018

The American Journal of Pathology

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Gastric cancer (GC) is the second leading cause of cancer-related mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes. Among other risk factors, Helicobacter pylori infection is considered the main driving factor of GC development. H. pylori infection increases DNA damage levels and leads to epigenetic dysregulation, which may favor gastric carcinogenesis. An early step in double-strand break repair is the recruitment of ataxia-telangiectasia mutated serine/threonine kinase (ATM) to the damaged site, where it plays a key role in advancing the DNA damage checkpoint process. H. pylori infection has been associated with the introduction of double-strand breaks in epithelial cells, triggering damage signaling and repair response involving ATM. Thus, the current study analyzed the effect of H. pylori infection on the DNA damage response sensor, ATM, in gastric epithelial cells and in biopsy specimens from patients with GC. In this study, we identified that H. pylori infection stimulated DNA damage, and therefore induced ATM in a virulence factor-dependent manner. In addition, we found that H. pylori might activate ATM through histone H3 and H4 hyperacetylation and DNA promoter hypomethylation. Our findings show a mechanism associating ATM signaling induction with H. pylori infection.

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Helicobacter pylori‐related risk predictors of gastric cancer: The latest models, challenges, and future prospects

2020

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Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co‐evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori‐related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry‐specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high‐risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age‐sex‐matched controls from high‐risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry‐specific. In addition, potential study‐level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled.

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Helicobacter pylori vacuolating cytotoxin genotypes and preneoplastic lesions or gastric cancer risk: a meta‐analysis

Abstract: The H. pylori vacA-s1 and vacA-m1 allelic variants strongly increased susceptibility to IM and GC; however, only s1 showed an association with AG. These associations were largely influenced by geographic variations in the GC incidence rate.

Cited by 20 publications

References 45 publications

Helicobacter pylori vacuolating cytotoxin and gastric cancer risk: reconsidered

Helicobacter pylori vacuolating cytotoxin and gastric cancer risk: reconsidered

Epigenetic Mechanisms of ATM Activation after Helicobacter pylori Infection

Helicobacter pylori‐related risk predictors of gastric cancer: The latest models, challenges, and future prospects

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