title: Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk.
abstract: OBJECTIVE
  Helicobacter pylori colonises the stomach in half of all humans, and is the principal cause of gastric cancer, the second leading cause of cancer death worldwide. While gastric cancer rates correlate with H pylori prevalence in some areas, there are regions where infection is nearly universal, but rates of gastric cancer are low. In the case of Colombia, there is a 25-fold increase in gastric cancer rate in the Andean mountain (high risk) region compared to the coastal (low risk) region, despite similarly high (∼90%) prevalence of H pylori in the two locations. Our aim was to investigate the ancestral origin of H pylori strains isolated from subjects in these high- and low-risk regions and to determine whether this is a predictive determinant of precancerous lesions.
  
  
  METHODS
  Multi-locus sequence typing was used to investigate phylogeographic origins of infecting H pylori strains isolated from subjects in the Pacific coast and Andes Mountains in the state of Nariño, Colombia. We analysed 64 subjects infected with cagA+ vacA s1m1 strains. Gastric biopsy slides from each individual were scored for histological lesions and evaluated for DNA damage by immunohistochemistry.
  
  
  RESULTS
  We show that strains from the high-risk region were all of European phylogeographic origin, whereas those from the low risk region were of either European (34%) or African origin (66%). European strain origin was strongly predictive of increased premalignant histological lesions and epithelial DNA damage, even in the low-risk region; African strain origin was associated with reduced severity of these parameters.
  
  
  CONCLUSIONS
  The phylogeographic origin of H pylori strains provides an explanation for geographic differences in cancer risk deriving from this infection.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, MRBIV, Room 1030C, 2215 Garland Avenue, Nashville, TN 37232, USA. keith.wilson@vanderbilt.edu
authors.forename: Thibaut
authors.initials: T
authors.lastname: de Sablet
authors.forename: M Blanca
authors.initials: MB
authors.lastname: Piazuelo
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Shaffer
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Schneider
authors.forename: Mohammad
authors.initials: M
authors.lastname: Asim
authors.forename: Rupesh
authors.initials: R
authors.lastname: Chaturvedi
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bravo
authors.forename: Liviu A
authors.initials: LA
authors.lastname: Sicinschi
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Delgado
authors.forename: Robertino M
authors.initials: RM
authors.lastname: Mera
authors.forename: Dawn A
authors.initials: DA
authors.lastname: Israel
authors.forename: Judith
authors.initials: J
authors.lastname: Romero-Gallo
authors.forename: Richard M
authors.initials: RM
authors.lastname: Peek
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Cover
authors.forename: Pelayo
authors.initials: P
authors.lastname: Correa
authors.forename: Keith T
authors.initials: KT
authors.lastname: Wilson
mesh_terms: D000328:Adult; D015373:Bacterial Typing Techniques; D001706:Biopsy; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004249:DNA Damage; D005753:Gastric Mucosa / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D011230:Precancerous Conditions / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology* / Q000473:pathology