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Recent studies have suggested that gastroesophageal reflux disease (GERD) increases the risk of developing adenocarcinoma of the distal esophagus and cardia. In order to further define this risk, we studied the relationship of GERD in patients with or without gastroesophageal junction adenocarcinomas.The records of all patients with adenocarcinoma of the distal esophagus and cardia treated between 1991 and 1999 were reviewed for the following data: gender, age of diagnosis, presence of GERD, presence of GERD for >4 years, and GERD treatment. A control group of patients without gastroesophageal junction adenocarcinoma were matched for age and gender. Data obtained from the control group included presence of GERD and treatment for GERD.60 patients with adenocarcinoma of the distal esophagus and cardia were identified. 40% of cancer patients had GERD at the time of diagnosis, (odds ratio 39, p < 0.0001). 27% of cancer patients had GERD for >4 years (odds ratio 21, p < 0.0001). 50% of cancer patients with GERD were being treated with either H2-blockers or proton pump inhibitors at the time of cancer diagnosis, with an average duration of treatment of 17 months, compared to none of the patients without GERD (p = 0.006).Patients with gastroesophageal junction adenocarcinoma had a higher prevalence of GERD-like symptoms compared to age- and gender-matched controls. This supports an association between GERD and gastroesophageal junction cancers. In addition, cancer patients with GERD may be treated for prolonged periods of time with acid-suppression medication prior to the diagnosis of cancer, masking the symptoms of cancer. Patients with long-standing GERD or older patients with new onset GERD may need endoscopy or imaging studies to evaluate for cancer of the distal esophagus or cardia.