title: Relevance of Helicobacter pylori vacA 3'-end Region Polymorphism to Gastric Cancer.
abstract: BACKGROUND
  Helicobacter pylori vacA genotypes play an important role in the pathogenesis of severe gastrointestinal disease.
  
  
  METHODS
  We identified a novel polymorphic site in the 3'-end region of H. pylori vacA gene, denoted by c1/-c2 (c1: with deletion of 15 bp), and examined associations of this and the previous four sites as well as cagA status with gastroduodenal diseases, in a total of 217 Iranian H. pylori isolates. Histopathologic evaluations were performed and patients with gastric cancer (GC) were further classified based on the anatomic site of tumor, including cardia and noncardia GC, and the histopathologic type of tumor, including intestinal- and diffuse-type GC.
  
  
  RESULTS
  The vacA m1, i1, d1, c1, and cagA genotypes were significantly associated with an increased risk of GC, the odds ratio (95% confidence interval) was 4.29 (2.03-9.08), 6.11 (2.63-14.19), 3.18 (1.49-6.76), 15.13 (5.86-39.01), and 2.59 (1.09-6.12), respectively. The vacA c1 genotype had an increased age- and sex-adjusted risk for GC by the multiple logistic regression analysis; the OR was 38.32 (95% CI, 6.60-222.29). This association was independent of and larger than the associations of the m-, i-, and d-type of vacA or cagA status with GC. No significant correlation was found between s1, whether independently or in combination, and the risk of GC or peptic ulcer disease (PUD). The vacA i1 and cagA genotypes were linked to an increased risk of PUD; the OR (95% CI) was 2.80 (1.45-5.40) and 2.62 (1.23-5.61), respectively. The presence of both the vacA i1 and cagA genotypes further increased the risk of PUD; the OR was 5.20 (95% CI, 1.92-14.03).
  
  
  CONCLUSIONS
  The H. pylori vacA c1 genotype might therefore be one of the strongest risk predictors of GC in male patients aged ≥55 in Iran.
authors.affiliation: Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
authors.forename: Seyedeh Zahra
authors.initials: SZ
authors.lastname: Bakhti
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: Shiva
authors.initials: S
authors.lastname: Mohammadi
authors.affiliation: Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran.
authors.forename: Saber
authors.initials: S
authors.lastname: Zahri
authors.affiliation: Department of Biostatistics, Faculty of Public Health, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Fatemeh Sadat
authors.initials: FS
authors.lastname: Bakhti
authors.affiliation: Aras Clinics, Imam Khomeini Hospital, Ardabil University of Medical Sciences, Ardabil, Iran.
authors.forename: Farideh
authors.initials: F
authors.lastname: Feizi
authors.affiliation: Gastrointestinal Cancer Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Yazdanbod
authors.affiliation: Department of Microbiology, School of Biology, University College of Sciences, University of Tehran, Tehran, Iran.
authors.forename: Farideh
authors.initials: F
authors.lastname: Siavoshi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications* / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori
keywords: H. pylori; cagA; gastric cancer; genotyping; vacA 3ʹ-end region