J. Lagergren and Others
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001
Reviewers: Kenneth Blank, MD
Source: The New England Journal of Medicine Volume 340, Number 11: March 18, 1999
Symptoms of gastroesophageal reflux (heartburn) may be related to the onsetof esophageal cancer. Heartburn is known to play an important role in thedevelopment of Barrett?s esophagus (a pre-cancerous condition of theesophagus), but little evidence exists linking reflux symptoms directly toesophageal cancer. A March 18th report in the New England Journal ofMedicine examines the relationship between heartburn and the risk ofesophageal cancer and cancer of the gastric cardia.
Tumors were carefully examined endoscopically and pathologically toclassify them properly as either gastric cardia cancers or esophagealcancers. Tumors that had their epicenters within two centimeters proximalor three centimeters distal to the gastroesophageal junction wereconsidered gastric cardia. The gastroesophageal junction was defined as thepoint where the proximal longitudinal mucosal folds begin in the stomach.
Professional interviewers using a computer assisted program obtained dataon reflux symptoms including heartburn and regurgitation. The interviewerswere not blinded to the patients diagnosis (case or control) but had noknowledge of the study hypothesis. To prevent collecting data on symptomscaused by the cancer, only symptoms that were present for at least fiveyears prior to study entry were included.
Reflux symptoms were associated with adenocarcinoma of the gastric cardia,but not as strongly as with esophageal adenocarcinoma. Symptoms were gradedby severity and frequency on a scale from 0-6.5, with higher scoresindicating worse and more frequent symptoms. Persons with high scores had anearly three fold increase in the risk of adenocarcinoma of the gastriccardia. Duration of symptoms also increased risk; persons with eitherheartburn or regurgitation greater than twenty years had a four foldincrease in the risk of gastric cardia adenocarcinoma.
Esophageal squamous cell carcinoma was not associated with heartburn orregurgitation regardless of the frequency, severity or duration ofsymptoms. Several confounding factors for esophageal cancer (adenocarcinomaand/or squamous carcinoma) were identified including Barrett?s esophagus,age, sex, body-mass index, smoking and alcohol use. However, none of theserisk factors significantly changed the risk estimates.
The clinical implications of this study are unclear. Should everyone withreflux symptoms be endoscoped to rule-out carcinoma? Since twenty percentof the adult population in the United States complains of heartburn weekly,such a policy would have a remarkably low yield and place a great burden ona medical system already strained financially. Instead, further studies arenecessary to define a group of patients with heartburn who are atsufficiently high risk of cancer that screening endoscopy is warranted.
Further studies are also necessary to determine the best treatment ofheartburn. Presently, many medications are effective at alleviating reflux symptoms including antacids, H2 blockers (cimetidine, ranitidine, famotidine, and nizatidine) andproton-pump inhibitors (such as lansoprazole and omeprazole).
However whether or not these medications will decrease the risk of canceris unknown. Clearly, heartburn is not a benign symptom and places patientsat risk for esophageal adenocarcinoma and gastric cardia adenocarcinoma.Patients with heartburn, and especially those with severe or long-standingsymptoms, should consult a physician for a complete evaluation.