title: Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: a long-term follow-up in a high-risk area in Spain.
abstract: OBJECTIVE
  There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions.
  
  
  METHODS
  This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression.
  
  
  RESULTS
  The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR)=2.28, 95% confidence interval (CI) 1.13-4.58; OR=2.90, 95% CI 1.38-6.13; and OR=3.38, 95% CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95% CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains.
  
  
  CONCLUSIONS
  H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.
authors.affiliation: Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (IDIBELL-ICO), Barcelona, Spain. cagonzalez@iconcologia.net
authors.forename: Carlos A
authors.initials: CA
authors.lastname: González
authors.forename: Ceu
authors.initials: C
authors.lastname: Figueiredo
authors.forename: C Bonet
authors.initials: CB
authors.lastname: Lic
authors.forename: R M
authors.initials: RM
authors.lastname: Ferreira
authors.forename: M L
authors.initials: ML
authors.lastname: Pardo
authors.forename: J M
authors.initials: JM
authors.lastname: Ruiz Liso
authors.forename: P
authors.initials: P
authors.lastname: Alonso
authors.forename: N
authors.initials: N
authors.lastname: Sala
authors.forename: G
authors.initials: G
authors.lastname: Capella
authors.forename: J M
authors.initials: JM
authors.lastname: Sanz-Anquela
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001707:Biopsy, Needle; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005757:Gastritis, Atrophic / Q000473:pathology; D005773:Gastroscopy; D005838:Genotype; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000382:microbiology / Q000473:pathology*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000382:microbiology / Q000473:pathology*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori