Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status.
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.
Hansen
Svein
S
The Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway.
Vollset
Stein Emil
SE
Derakhshan
Mohammad H
MH
Fyfe
Valerie
V
Melby
Kjetil K
KK
Aase
Steinar
S
Jellum
Egil
E
McColl
Kenneth E L
KE
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
D015415:Biomarkers; D005755:Gastrins; D020115:Pepsinogen C; D020116:Pepsinogen A