A review of epidemiological studies on cancer in relation to the use of anti-ulcer drugs

H2-receptor antagonists have been widely used since the late 1970s for the treatment of gastrointestinal ulcers and other benign conditions of the stomach, oesophagus and duodenum. Several case reports suggested that long-term therapy with H2-receptor antagonists, mainly cimetidine and ranitidine, might increase the risk of gastric cancer. After early case reports, at least six analytical epidemiological studies (two cohort and four case-control) were published, including a total of about 1000 cases of gastric cancer. The relative risks (RR) were systematically and substantially elevated in the first year since starting H2-receptor antagonist use, and levelled off in the following years. Some excess risk was still apparent during the first 5 years of drug use, probably due to incorrect diagnosis and treatment of pre-existing neoplastic gastric lesions, but the estimated RR was not above unity for ≥10 years since starting drug treatment in the two studies including information on long-term use. The findings of analytical epidemiological studies are thus consistent with the absence of a causal association between H2-receptor antagonist use and gastric cancer risk. Data on oesophageal and colorectal cancer do not support a relevant relation between cimetidine use and the risk of these neoplasms. With reference to total cancer mortality, in a Danish cohort study, for males the RR was 1.9 in the first year, and 1.4 in the first 5 years; corresponding values for females were 1.7 and 1.5. In a British cohort study, the RR was 3.4 in the first year, and 1.3 in the years 2-10. The excess risk in the first year was essentially due to gastric cancer. Post-marketing surveillance data for omeprazole and other proton pump inhibitors are much scantier than for H2-receptor antagonists, particularly on long-term use.