The Association between Ranitidine Use and Gastrointestinal Cancers

SIMPLE SUMMARY: N-nitrosodimethylamine (NDMA) is a carcinogen in experimental animals and has been classified a probable human carcinogen. NDMA has been identified in samples of ranitidine. Observational studies have demonstrated a relationship between dietary and occupational exposure to NDMA and specific cancers, principally to the gastrointestinal system. Studies focused on ranitidine exposure are lacking. This study evaluated the association between ranitidine exposure and gastrointestinal cancer using a comparison group that minimizes confounding by indication. ABSTRACT: N-nitrosodimethylamine (NDMA) is a carcinogen in experimental animals. It has been classified a probable human carcinogen and has been found in ranitidine. This study sought to evaluate the association between ranitidine use and cancer of the gastrointestinal system. Events reported to the FDA Adverse Events Reporting System that were associated with the use of proton pump inhibitors (PPIs) and H(2) antagonists were selected. Proportionate reporting ratios (PRRs) and associated 95% confidence intervals (CIs) were calculated to compare the proportion of all reported adverse events that were for gastrointestinal system cancers among adverse event reports for ranitidine to adverse event reports for other H(2) antagonists. The proportion of adverse events for any gastrointestinal system cancer relative to all other events was elevated for ranitidine compared to PPIs and other H(2) antagonists (PRR 3.66, 95% CI 3.19–4.20). Elevated and significant PRRs were observed for pharyngeal (PRR 9.24), esophageal (PRR 3.56), stomach (PRR 1.48), colorectal (PRR 16.31), liver (PRR 2.64), and pancreatic (PRR 2.18) cancers. The PRRs for anal (PRR 4.62) and gallbladder (PRR 4.62) cancer were also elevated though not statistically significant. In conjunction with a large body of epidemiologic and human and animal basic science research, the study results support the hypothesis that NDMA-contaminated ranitidine increases the risk of cancer and supports the withdrawal of these medications from the market.