title: Analysis of cagA in Helicobacter pylori strains from Colombian populations with contrasting gastric cancer risk reveals a biomarker for disease severity.
abstract: BACKGROUND
  Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis.
  
  
  METHODS
  We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain.
  
  
  RESULTS
  A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathologic analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif.
  
  
  CONCLUSIONS
  CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk.
  
  
  CONCLUSIONS
  These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Loh
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Shaffer
authors.forename: M Blanca
authors.initials: MB
authors.lastname: Piazuelo
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bravo
authors.forename: Mark S
authors.initials: MS
authors.lastname: McClain
authors.forename: Pelayo
authors.initials: P
authors.lastname: Correa
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D015331:Cohort Studies; D003105:Colombia; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications* / Q000235:genetics / Q000382:microbiology; D016480:Helicobacter pylori / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D059372:Nucleotide Motifs; D011230:Precancerous Conditions / Q000209:etiology / Q000473:pathology; D011379:Prognosis; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology* / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014408:Biomarkers, Tumor; D004269:DNA, Bacterial; C080866:cagA protein, Helicobacter pylori