Methods We performed a nationwide, population-based, case-control study in Sweden. Case ascertainment was rapid, and all cases were classified uniformly. information on the subjects' history of gastroesophageal reflux was collected in personal interviews. The odds ratios were calculated by logistic regression, with multivariate adjustment for potentially confounding variables.

Results Of the patients interviewed, the 189 with esophageal adenocarcinoma and the 262 with adenocarcinoma of the cardia constituted 85 percent of the 529 patients in Sweden who were eligible for the study during the period from 1995 through 1997. For comparison, we interviewed 820 control subjects from the general population and 167 patients with esophageal squamous-cell carcinoma. Among persons with recurrent symptoms of reflux, as compared with persons without such symptoms, the odds ratios were 7.7 (95 percent confidence interval, 5.3 to 11.4) for esophageal adenocarcinoma and 2.0 (95 percent confidence interval, 1.4 to 2.9) for adenocarcinoma of the cardia. The more frequent, more severe, and longer-lasting the symptoms of reflux, the greater the risk. Among persons with long-standing and severe symptoms of reflux, the odds ratios were 43.5 (95 percent confidence interval, 18.3 to 103.5) for esophageal adenocarcinoma and 4.4 (95 percent confidence interval, 1.7 to 11.0) for adenocarcinoma of the cardia. The risk of esophageal squamous-cell carcinoma was not associated with reflux (odds ratio, 1.1; 95 percent confidence interval, 0.7 to 1.9).

Conclusions There is a strong and probably causal relation between gastroesophageal reflux and esophageal adenocarcinoma. The relation between reflux and adenocarcinoma of the gastric cardia is relatively weak. (N Engl J Med 1999; 340:825-31.) (C) 1999, Massachusetts Medical Society.