Article Text

Download PDFPDF
Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status
  1. Svein Hansen1,
  2. Stein Emil Vollset2,
  3. Mohammad H Derakhshan3,
  4. Valerie Fyfe3,
  5. Kjetil K Melby4,
  6. Steinar Aase5,
  7. Egil Jellum6,
  8. Kenneth E L McColl3
  1. 1The Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway
  2. 2Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
  3. 3Division of Medical Sciences, Western Infirmary, University of Glasgow, Glasgow, UK
  4. 4Department of Microbiology, Ullevaal University Hospital, Oslo, Norway
  5. 5Department of Pathology, Haukeland University Hospital, University of Bergen, Bergen, Norway
  6. 6Institute of Clinical Biochemistry, Rikshospitalet, University of Oslo, Oslo, Norway
  1. Correspondence to:
    Professor K E L McColl
    Division of Medical Sciences, Western Infirmary, University of Glasgow, Glasgow G11 6NT, UK; k.e.l.mccoll{at}


Background: Non-cardia gastric adenocarcinoma is positively associated with Helicobacter pylori infection and atrophic gastritis. The role of H pylori infection and atrophic gastritis in cardia cancer is unclear.

Aim: To compare cardia versus non-cardia cancer with respect to the premorbid state of the stomach.

Methods: Nested case–control study. To each of 129 non-cardia and 44 cardia cancers, three controls were matched. Serum collected a median of 11.9 years before the diagnosis of cancer was tested for anti-H pylori antibodies, pepsinogen I:II and gastrin.

Results: Non-cardia cancer was positively associated with H pylori (OR 4.75, 95% CI 2.56 to 8.81) and gastric atrophy (pepsinogen I:II <2.5; OR 4.47, 95% CI 2.71 to 7.37). The diffuse and intestinal histological subtypes of non-cardia cancer were of similar proportions and both showed a positive association with H pylori and atrophy. Cardia cancer was negatively associated with H pylori (OR 0.27, 95% CI 0.12 to 0.59), but H pylori-positive cardia cancer showed an association with gastric atrophy (OR 3.33, 95% CI 1.06 to 10.5). The predominant histological subtype of cardia cancer was intestinal and was not associated with gastric atrophy compared with the diffuse subtype ((OR 0.72, 95% CI 0.19 to 2.79) vs (OR 3.46, 95% CI 0.32 to 37.5)). Cardia cancer in patients with atrophy had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1), whereas cardia cancers in patients without atrophy were predominantly intestinal (7:1).

Conclusion: These findings indicate two aetiologies of cardia cancer, one associated with H pylori atrophic gastritis, resembling non-cardia cancer, and the other associated with non-atrophic gastric mucosa, resembling oesophageal adenocarcinoma. Serological markers of gastric atrophy may provide the key to determining gastric versus oesophageal origin of cardia cancer.

  • PGI:II, pepsinogen I to pepsinogen II ratio

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Published Online First 22 February 2007

  • Competing interests: None.

Linked Articles