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Two distinct aetiologies of cardia cancer; evidence from premorbid serological markers of gastric atrophy and H. pylori status
  1. Svein Hansen (svein.hansen{at}
  1. The Cancer Registry of Norway, Norway
    1. Stein Emil Vollset
    1. University of Bergen, Norway
      1. Mohammad H. Derakhshan
      1. University of Glasgow, United Kingdom
        1. Valerie Fyfe
        1. University of Glasgow, United Kingdom
          1. Kjetil K. Melby
          1. Ullevaal University Hospital, Norway
            1. Steinar Aase
            1. University of Bergen, Norway
              1. Egil Jellum
              1. University of Oslo, Norway
                1. Kenneth E.L. McColl (k.e.l.mccoll{at}
                1. University of Glasgow, United Kingdom


                  Background: Non-cardia gastric adenocarcinoma is positively associated with H. 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, 3 controls were matched. Serum collected a median of 11.9 years before cancer diagnosis 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 2.56-8.81) and gastric atrophy (pepsinogen I/II <2.5) (OR 4.47, 2.71- 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, 0.12-0.59), but H.pylori positive cardia cancer showed a positive association with gastric atrophy (OR 3.33, 1.06-10.5). The predominant histological subtype of cardia cancer was intestinal and it was not associated with gastric atrophy compared to the diffuse subtype [(0.72, 0.19-2.79) vs. (3.46, 0.32- 37.5)]. Cardia cancer in atrophic patients had an intestinal: diffuse ratio (1:1) similar to non-cardia cancer (1.9:1) whereas cardia cancers in persons 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.

                  • atrophic gastritis
                  • gastric cardia cancer
                  • H. pylori
                  • pepsinogen ratio

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