title: Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status.
abstract: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
authors.forename: Svein
authors.initials: S
authors.lastname: Hansen
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Derakhshan
authors.forename: Valerie
authors.initials: V
authors.lastname: Fyfe
authors.forename: Kjetil K
authors.initials: KK
authors.lastname: Melby
authors.forename: Steinar
authors.initials: S
authors.lastname: Aase
authors.forename: Egil
authors.initials: E
authors.lastname: Jellum
authors.forename: Kenneth E L
authors.initials: KE
authors.lastname: McColl
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000382:microbiology / Q000473:pathology; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002299:Cardia; D016022:Case-Control Studies; D005260:Female; D005755:Gastrins / Q000097:blood; D005757:Gastritis, Atrophic / Q000150:complications* / Q000175:diagnosis; D016481:Helicobacter Infections / Q000150:complications* / Q000175:diagnosis; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D020115:Pepsinogen C / Q000097:blood; D011230:Precancerous Conditions / Q000097:blood; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000209:etiology* / Q000382:microbiology / Q000473:pathology
chemical_list: D015415:Biomarkers; D005755:Gastrins; D020115:Pepsinogen C; D020116:Pepsinogen A