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Phylogeographic origin of Helicobacter pylori is a determinant of gastric cancer risk
  1. Thibaut de Sablet1,2,
  2. M Blanca Piazuelo1,
  3. Carrie L Shaffer3,
  4. Barbara G Schneider1,
  5. Mohammad Asim1,2,
  6. Rupesh Chaturvedi1,2,
  7. Luis E Bravo4,
  8. Liviu A Sicinschi1,
  9. Alberto G Delgado1,
  10. Robertino M Mera1,
  11. Dawn A Israel1,
  12. Judith Romero-Gallo1,
  13. Richard M Peek Jr1,2,5,
  14. Timothy L Cover2,3,6,
  15. Pelayo Correa1,
  16. Keith T Wilson1,2,5
  1. 1Division of Gastroenterology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, USA
  2. 2Veterans Affairs Tennessee Valley Healthcare System, Nashville, USA
  3. 3Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, USA
  4. 4Department of Pathology, Universidad del Valle School of Medicine, Cali, Colombia
  5. 5Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, USA
  6. 6Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, USA
  1. Correspondence to Professor Keith T Wilson, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, MRBIV, Room 1030C, 2215 Garland Avenue, Nashville, TN 37232, USA; keith.wilson{at}vanderbilt.edu

Abstract

Background and aims 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.

Conclusion The phylogeographic origin of H pylori strains provides an explanation for geographic differences in cancer risk deriving from this infection.

  • Gastric cancer
  • Helicobacter pylori
  • multi-locus sequence typing
  • DNA damage
  • gastritis
  • intestinal metaplasia
  • gastric atrophy
  • Helicobacter pylori infection
  • histopathology

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Footnotes

  • Funding This work was supported by the National Institute of Health grants P01CA028842 (PC, KTW), R01DK053620 (KTW), R01AT004821 (KTW), P01CA116087 (RMP, TLC, KTW), UL1RR024975 (Vanderbilt CTSA, KTW), R01AI039657 (TLC), R01AI068009 (TLC), R01DK58587 (RMP), R01CA77955 (RMP), and P30DK058404 (Vanderbilt Digestive Disease Research Center); Merit Review Grants from the Department of Veterans Affairs (KTW, TLC); and the Philippe Foundation (TS).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Universidad del Valle in Cali, Colombia; and Vanderbilt University, Nashville, Tennessee, USA.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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