THE RELATION OF GASTROESOPHAGEAL REFLUX DISEASE AND ITS TREATMENT TO ADENOCARCINOMAS OF THE ESOPHAGUS AND GASTRIC CARDIA

Objective.-To examine the relationship of gastrointestinal disorders a nd their treatment to the risk of adenocarcinomas of the esophagus and gastric cardia (AEC). Design.-A medical record-based case-control stu dy, with data collected on a standardized form by a trained abstractor , blind to the case-control status. Setting.-A large prepaid health pl an. Subjects.-Case patients were plan members newly diagnosed with his tologically confirmed AEC from 1986 to 1992. For each of the 196 eligi ble case patients, one control was selected who matched for membership at time of diagnosis, sex, year of birth, and duration of membership. Main Outcome Measures.-Association between AEC and history of gastroe sophageal conditions and their treatment. Conditional logistic regress ion procedures were used for calculation of odds ratios (ORs) and corr esponding 95% confidence intervals (Cls), with adjustment for race, sm oking status, and body mass index. Medications were grouped into H-2 a ntagonists (cimetidine, ranitidine, famotidine, and nizatidine) and an ticholinergics (propantheline bromide, dicyclomine hydrochloride, Donn atal [combination of atropine sulfate, hyoscyamine sulfate, phenobarbi tal, and scopolamine hydrobromide], and Librax [combination of chlordi azepoxide hydrochloride and clidinium bromide]). Results.-Significant twofold or greater risks of AEC were associated with a history of esop hageal reflux, hiatal hernia, esophagitis/esophageal ulcer, and diffic ulty swallowing. The ORs increased with increasing number of these con ditions. Although a fourfold risk was linked to four or more prescript ions for H-2 antagonists, the risk was reduced to 1.5 (95% CI, 0.4 to 5.4) after adjusting for the predisposing conditions. Further analysis revealed that the excess risk was restricted to persons with a histor y of gastroesophageal reflux and related conditions. No association wa s observed for overall use of anticholinergics. However, after adjustm ent for predisposing conditions, ORs decreased with increasing number of prescriptions for anticholinergics (P for trend=.08). Conclusions.- This study provides reassuring findings that use of H-2 antagonists an d anticholinergics does not increase AEC risk. It also quantifies the elevated risk of AEC associated with gastroesophageal reflux disease. Further research into reflux disease and the production of premalignan t epithelial changes may help elucidate carcinogenic mechanisms and me asures aimed at early detection and prevention of AEC.