Patterns of Acid-Suppressive Therapy and Cancer Risk

Background: Whether proton pump inhibitors (PPIs) or H2 antagonists influence cancer risk remains uncertain, partly due to confounding by indication and reverse causation. We analyzed prescribing patterns in a large dataset to characterize lifetime and pre-diagnostic exposure to PPIs and H2 antagonists across cancer types, with emphasis on upper gastrointestinal (GI) malignancies. Methods: We examined 3,390,218 adults in the NHS with linked medication and cancer coding, identifying lifetime acid-suppressive use and, for cancer cases, exposure during the 5 years preceding diagnosis. Patients with oesophageal, stomach, pancreatic, or biliary tract cancers were specifically compared with cancer-free controls. Age-specific 10-year PPI and H2 antagonist prevalence was calculated, and odds ratios (ORs) for ever-use were derived using cancer-free individuals as comparators. Results: There were 1,078 oesophageal, 527 stomach, 696 pancreatic, and 130 biliary tract cancer patients. Lifetime PPI exposure differed markedly by cancer type: 93% of oesophageal cancer patients (OR=35.0), 89% of stomach cancer patients (OR=21.2), and 65-75% of other cancer types reported PPI use, compared with 3-55% among age-matched controls. H2 antagonist use showed weaker associations (OR 1.6-2.0). In the 5-year pre-diagnostic interval, PPI exposure was highest in oesophageal (93.0%), stomach (89.0%), pancreatic (88.6%), and biliary tract cancers (87.7%), with a median duration of 84 days. Duration of pre-diagnostic PPI use showed a strong gradient unique to upper-GI cancers; no similar gradient was seen for H2 antagonists. Several non-GI cancers, including laryngeal cancer, also demonstrated elevated PPI use, though to a slightly lesser extent. Conclusions: PPI exposure, both lifetime use and 5-year pre-diagnostic duration, was substantially higher among upper-GI cancer patients than among age-matched controls. While this may reflect symptom-driven escalation of therapy in the period preceding diagnosis, the consistently elevated exposure across multiple cancers raises the possibility that PPIs themselves may contribute to carcinogenic processes. The absence of comparable associations for H2 antagonists suggests that acid suppression alone does not explain the observed patterns. Pronounced PPI enrichment in upper-GI cancers, weaker signals for H2 antagonists, and detectable associations in selected non-GI cancers underscore the need for further work to determine whether PPIs act solely as markers of prodromal symptomatology or may exert independent effects relevant to cancer development. Citation Format: M Payling, Bea Bakshi, Marta Sakal. Patterns of acid-suppressive therapy prescriptions in cancer: Are we treating symptoms or fueling the disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5493.