GASTRIC CANCER

Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and Helicobacter pylori status

Svein Hansen¹, Stein Emil Vollset², Mohammad H Derakhshan³, Valerie Fyfe³, Kjetil K Melby⁴, Steinar Aase⁵, Egil Jellum⁶, Kenneth E L McColl³

¹ The Cancer Registry of Norway, Institute of Population-based Cancer Research, Oslo, Norway
² Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
³ Division of Medical Sciences, Western Infirmary, University of Glasgow, Glasgow, UK
⁴ Department of Microbiology, Ullevaal University Hospital, Oslo, Norway
⁵ Department of Pathology, Haukeland University Hospital, University of Bergen, Bergen, Norway
⁶ Institute of Clinical Biochemistry, Rikshospitalet, University of Oslo, Oslo, Norway

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}clinmed.gla.ac.uk

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.

Abbreviations: PGI:II, pepsinogen I to pepsinogen II ratio

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