Combination of gastric atrophy, reflux symptoms and histological subtype indicates two distinct aetiologies of gastric cardia cancer

Introduction: Atrophic gastritis is a risk factor for non-cardia gastric cancer, and gastro-oesophageal reflux disease (GORD) for oesophageal adenocarcinoma. The role of atrophic gastritis and GORD in the aetiology of adenocarcinoma of the cardia remains unclear. We have investigated the association between adenocarcinoma of the different regions of the upper gastrointestinal tract and atrophic gastritis and GORD symptoms. Methods: 138 patients with upper GI adenocarcinoma and age- and sex-matched controls were studied. Serum pepsinogen I/II was used as a marker of atrophic gastritis and categorised to five quintiles. History of GORD symptoms, smoking and H pylori infection were incorporated in logistic regression analysis. Lauren classification of gastric cancer was used to subtype gastric and oesophageal adenocarcinoma. Results: Non-cardia cancer was associated with atrophic gastritis but not with GORD symptoms; 55% of these cancers were intestinal subtype. Oesophageal adenocarcinoma was associated with GORD symptoms, but not with atrophic gastritis; 84% were intestinal subtype. Cardia cancer was positively associated with both severe gastric atrophy [OR, 95% CI: 3.92 (1.77 to 8.67)] and with frequent GORD symptoms [OR, 95% CI: 10.08 (2.29 to 44.36)] although the latter was only apparent in the non-atrophic subgroup and in the intestinal subtype. The association of cardia cancer with atrophy was stronger for the diffuse versus intestinal subtype and this was the converse of the association observed with non-cardia cancer. Conclusion: These findings indicate two distinct aetiologies of cardia cancer, one arising from severe atrophic gastritis and being of intestinal or diffuse subtype similar to non-cardia cancer, and one related to GORD and intestinal in subtype, similar to oesophageal adenocarcinoma. Gastric atrophy, GORD symptoms and histological subtype may distinguish between gastric versus oesophageal origin of cardia cancer.