title: Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma.
abstract: BACKGROUND
  Both Helicobacter pylori genotype and host genetic polymorphisms play a role in determining the clinical consequences of H. pylori infection. We investigated whether there are any combinations of bacterial and host genotypes that are particularly associated with the occurrence of gastric carcinoma.
  
  
  METHODS
  Genotypic variations in virulence-associated genes of H. pylori vacA (s and m regions) and cagA were determined in 221 subjects with chronic gastritis and 222 patients with gastric carcinoma by polymerase chain reaction (PCR)-line probe assay. Polymorphisms in the human interleukin 1 beta (IL-1B) gene (IL-1B-511*C or IL-1B-511*T) and in the IL-1 receptor antagonist gene (IL-1RN intron 2 variable number of tandem repeats) were evaluated by PCR and single-strand conformation polymorphism analysis. All statistical tests were two-sided.
  
  
  RESULTS
  Infection with vacAs1-, vacAm1-, and cagA-positive strains of H. pylori was associated with an increased risk for gastric carcinoma, with odds ratios (ORs) of 17 (95% confidence interval [CI] = 7.8 to 38), 6.7 (95% CI = 3.6 to 12), and 15 (95% CI = 7.4 to 29), respectively. IL-1B-511*T carriers (IL-1B-511*T/*T or IL-1B-511*T/*C) homozygous for the short allele of IL-1RN (IL-1RN*2/*2) had an increased gastric carcinoma risk (OR = 3.3, 95% CI = 1.3 to 8.2). For each combination of bacterial/host genotype, the odds of having gastric carcinoma were greatest in those with both bacterial and host high-risk genotypes: vacAs1/IL-1B-511*T carrier (OR = 87, 95% CI = 11 to 679), vacAm1/IL-1B-511*T carrier (OR = 7.4, 95% CI = 3.2 to 17), cagA-positive/IL-1B-511*T carrier (OR = 25, 95% CI = 8.2 to 77), vacAs1/IL-1RN*2/*2 (OR = 32, 95% CI = 7.8 to 134), vacAm1/IL-1RN*2/*2 (OR = 8.8, 95% CI = 2.2 to 35), and cagA-positive/IL-1RN*2/*2 (OR = 23, 95% CI = 7.0 to 72).
  
  
  CONCLUSIONS
  Combined bacterial/host genotyping may provide an important tool in defining disease risk and targeting H. pylori eradication to high-risk individuals.
authors.affiliation: C. Figueiredo, Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal. cfigueiredo@ipatimup.pt
authors.forename: Céu
authors.initials: C
authors.lastname: Figueiredo
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Machado
authors.forename: Paul
authors.initials: P
authors.lastname: Pharoah
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Sónia
authors.initials: S
authors.lastname: Sousa
authors.forename: Ralph
authors.initials: R
authors.lastname: Carvalho
authors.forename: Ana Filipa
authors.initials: AF
authors.lastname: Capelinha
authors.forename: Wim
authors.initials: W
authors.lastname: Quint
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
authors.forename: Leen-Jan
authors.initials: LJ
authors.lastname: van Doorn
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000382:microbiology; D002908:Chronic Disease; D016001:Confidence Intervals; D005260:Female; D005756:Gastritis / Q000235:genetics / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000472:pathogenicity*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D008297:Male; D008679:Metaplasia / Q000382:microbiology; D008875:Middle Aged; D018598:Minisatellite Repeats; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007375:Interleukin-1; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori