title: Helicobacter pylori vacuolating cytotoxin genotypes and preneoplastic lesions or gastric cancer risk: a meta-analysis.
abstract: OBJECTIVE
  Disease progression to gastric cancer (GC) occurs in only a small proportion of Helicobacter pylori (H.  pylori) infected patients. The bacterium vacuolating cytotoxin A (vacA) gene polymorphisms may determine the clinical consequences. We examined the strength of this association in adult-infected populations and modeled the impact of mean age-standardized incidence rates (ASRs) of GC as a hypothesized moderator variable.
  
  
  METHODS
  Pooled relative risk (RR) estimates were calculated. Subgroup, sensitivity, and meta-regression analyses were conducted.
  
  
  RESULTS
  Totally, 33 studies (1446 cases/2697 controls) were analyzed. The vacA-s1 genotype was significantly associated with an increased risk of atrophic gastritis(AG), intestinal metaplasia(IM), and GC (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); however, the vacA m1 genotype strongly increased the risk of IM and GC, but not AG (RR = 1.571, 95% CI, 1.247-1.980 and RR = 1.431, 95% CI, 1.180-1.735, respectively). The vacA s1m1 allelic combination was linked to an increased risk of GC. The m1-type of vacA was more potent than s1 for predicting the risk of GC within the subgroups with the mean ASRs of 11/100,000-19/100,000 and less than 10/100,000. The meta-regression analysis indicated that the ASR of GC modified the association between H.  pylori genotypes and GC risk, where the estimated risk was significantly decreased with increasing the mean ASRs of GC (P-values = 0.025, 0.00009, and 0.0005 for s1, m1, and s1m1, respectively).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
authors.forename: Esmat
authors.initials: E
authors.lastname: Abdi
authors.affiliation: Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Latifi-Navid
authors.affiliation: Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Latifi-Navid
authors.affiliation: Department of Neurology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
authors.forename: Bahareh
authors.initials: B
authors.lastname: Safarnejad
mesh_terms: D000483:Alleles; D001426:Bacterial Proteins / Q000235:genetics*; D005757:Gastritis, Atrophic / Q000209:etiology; D014644:Genetic Variation; D005838:Genotype; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007422:Intestines / Q000473:pathology; D008679:Metaplasia / Q000209:etiology; D012044:Regression Analysis; D012306:Risk; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori
keywords: H. pylori genotypes; age-standardized incidence rate; gastric cancer; meta-analysis; meta-regression analysis