Is there a relationship? Esophageal cancer and ulcer medication.

Cancers of the esophagus and adjacent stomach tissue are among the most rapidly rising malignancies in the United States and other developed countries, according to many reports appearing in medical journals in recent years. Although the causes of these cancers are not well understood, there is some evidence that gastroesophageal reflux disease--conditions that permit stomach acid to back up into the lower end of the esophagus--may be involved.

The use of drugs to treat such conditions as esophageal reflux "heartburn" , hiatus hernia, esophagitis and esophageal ulcer, and swallowing difficulties--as well as the enormous popularity of antiulcer medications--has led to the hypothesis that these drugs may be a causative factor.

One such group of drugs is the anticholinergic agents--containing atropine, scopolamine, and other belladonna alkaloids--used to treat painful spasms of smooth muscle in the gastrointestinal tract. The lower esophageal sphincter is one such smooth muscle mass, which relaxes to allow food to pass into the stomach but then tightens to prevent reflux of stomach acid into the esophagus. The use of anticholinergic agents to relax smooth muscle spasm may allow such reflux to occur.

The drugs commonly used to treat peptic ulcer (histamine H2 receptor antagonists) have also been linked hypothetically to the increase in these cancers. The cardia--the particular portion of the stomach that joins the esophagus--lacks the acid and pepsin cells found elsewhere throughout the stomach lining. For reasons not well understood, the [H.sub.2] receptor antagonists have been suspected to play a role in the development of cancers of the cardia. Two of these drugs, ranitidine hydrochloride (Zantac) and cimetidine (Tagamet), are among the most frequently prescribed drugs in the world.

Given the widespread use of such drugs, which are now available over the counter, the need for epidemiological studies to evaluate their potential risk is evident. One such study, funded by the National Cancer Institute, was reported in the Journal of the American Medical Association, August 9, 1995. The study was conducted by the Southern California Permanente Group of Los Angeles--the Kaiser Foundation Health Plan serving more than two million members.

The case records of 196 plan members diagnosed with adenocarcinomas of the esophagus and gastric cardia from 1986 to 1992 were compared with the case records of 196 other members matched for membership at time of diagnosis, sex, year of birth, and duration of membership. The records were examined for the use of [H.sub.2] antagonists and anticholinergics. The former included ranitidine hydrochloride, cimetidine, nizatidine (Axid), and famotidine (Pepcid); the latter comprised dicyclomine hydrochloride (Bentyl), propantheline bromide (ProBanthAne), Donnatal, and Librax.

The researchers found that the risk of cancer was linked to long-term gastroesophageal reflux--but there was no difference between the cancer group and the control group insofar as the use of these drugs was concerned. They did point out, however, that "because [H.sub.2] antagonists have been available in the United States only since 1977, sufficient time may not have elapsed for this study to examine fully the late effect of these drugs."

The findings of no association between the use of these drugs and these cancers are reassuring. However, given the current TV advertising campaigns promoting the over-the-counter availability of some of the [H.sub.2] antagonists, it is likely that they will be used even more widely.

This, we believe, is unfortunate. Even if they have not been implicated in the development of gastroesophageal cancers, there is no reason for the majority of ulcer victims to depend upon the continued use of these very expensive drugs for symptomatic relief when a cure for their ulcers is readily available.

The cure, of course, is Dr. Barry Marshall's revolutionary antibiotic treatment of peptic ulcer. Although specialists in the treatment of gastrointestinal disease are now widely using the Marshall treatment, family practitioners seem to have been much slower in recognizing its validity. We suggest, therefore, that ulcer patients whose doctors have not yet recommended a course of antibiotic therapy might do well to discuss the possibility with them. If they have doubts about the validity of the Marshall treatment, they can fax their questions to him at this number: 804-977-8760.

Alternatively, patients willing to invest $25 in the hope of curing their disease can obtain a physician's information packet from the International Research Foundation for Helicobacter and Intestinal Immunology. (The $25 is a donation to Dr. Marshall's foundation, which uses it for upkeep of its information service and for research scholarships. The packet contains exact details for using the treatment, as well as the latest research reports and a list of doctors throughout the United States who are experienced in its use. For instructions and information, phone [phone].