Drugs that cause stomach acid to flow back into the esophagus may be to blame for about 10% of cases of a type of esophageal cancer that is on the rise, according to new study findings. But researchers suggest that the benefits of the drugs may outweigh any cancer risk.

For unknown reasons, a type of esophageal cancer called esophageal adenocarcinoma, which affects mostly men, has been on the rise in recent years. One potential cause for the increase, according to researchers at the Karolinska Institute in Stockholm, Sweden, is a condition called gastroesophageal reflux. This occurs when the contents of the stomach flow back into the esophagus, which can cause severe heartburn. While reflux can occur naturally, several medications can trigger it as well.

To test the link between cancer of the esophagus and drugs that cause reflux, Dr. Jesper Lagergren and colleagues compared 618 people with three types of esophageal cancer to 820 who did not have cancer. The investigators tracked the participants' use of five classes of drugs that can cause gastroesophageal reflux, including some used to treat heart disease and anxiety.

People who used at least one of several types of medications known to cause reflux were more likely to have esophageal adenocarcinoma. The increased risk was not statistically significant for people who had taken such drugs for 5 years or less, but the risk of this type of cancer was more than doubled compared to nonusers of the drugs in those who took at least one of the drugs for longer than 5 years.

Just 6.6% of people who did not have cancer had taken one of the drugs for more than 5 years, compared with 17.5% of people with esophageal adenocarcinoma.

There was no apparent link between use of the drugs and other types of esophageal cancer, according to the report.

One class of drugs called anticholinergics was linked most strongly to esophageal cancer, the report indicates. The good news, the researchers note, is that these drugs, which are used to treat a variety of gastrointestinal symptoms, are not prescribed as often as in the past.

Despite the apparent connection between cancer and drugs that trigger gastroesophageal reflux, Lagergren told Reuters Health that although esophageal adenocarcinoma is on the rise, it is still rare, even in people who use the drugs in the study. "There is certainly no need to stop using these drugs, particularly since the benefits of the use are often substantial," Lagergren said.

Drugs that cause gastroesophageal reflux probably explain just part of the increase in cases of esophageal cancer, according to Dr. Glenn M. Eisen, of Vanderbilt University Medical Center in Nashville, Tennessee. Ever-growing waistlines may be part of the problem, since obesity increases the risk of gastroesophageal reflux, he points out in an accompanying editorial. He also notes that ulcer rates have been dropping as rates of gastroesophageal reflux have been climbing, suggesting that efforts to eradicate an ulcer-causing bacterium called Helicobacter pylori may lead to increased esophageal troubles.

Eisen serves as a consultant to several pharmaceutical companies, including Searle Pharmaceuticals, Merck and Co., and Novartis. He also serves as a speaker for AstraZeneca.

Annals of Internal Medicine August 1, 2000;133:165-175, 227-229