Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK

• Published in: Gut Vol. 55; no. 11; pp. 1538 - 1544
• Main Authors: Rodríguez, L A García, Lagergren, J, Lindblad, M
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Society of Gastroenterology 01-11-2006; BMJ Publishing Group LTD; BMJ Group
• Subjects: Acids; Adenocarcinoma - chemically induced; Adenocarcinoma - epidemiology; Adult; Aged; Aged, 80 and over; Antacids - administration & dosage; Antacids - adverse effects; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - adverse effects; BMI; body mass index; Cancer therapies; Cardia; Confounding (Statistics); Drug Administration Schedule; Epidemiologic Methods; Esophageal Neoplasms - chemically induced; Esophageal Neoplasms - epidemiology; gastric acid suppression; Gastric cancer; gastro-oesophageal reflux disease; general practitioner; general practitioners research database; GORD; GPRD; H2 blockers; histamine H2 antagonists; Histamine H2 Antagonists - administration & dosage; Histamine H2 Antagonists - adverse effects; histamine2 receptor antagonists; Humans; Medicin och hälsovetenskap; Middle Aged; odds ratio; oesophageal adenocarcinoma; Patients; PPI; Prescriptions; proton pump inhibitor; Proton Pump Inhibitors; Stomach; Stomach Neoplasms - chemically induced; Stomach Neoplasms - epidemiology; Ulcers; United Kingdom - epidemiology; United Kingdom > UK
• ISSN: 0017-5749; 1468-3288
• DOI: 10.1136/gut.2005.086579

Background: Gastric acid suppressing drugs (that is, histamine2 receptor antagonists and proton pump inhibitors) could affect the risk of oesophageal or gastric adenocarcinoma but few studies are available. Aims: To study the association between long term treatment with acid suppressing drugs and the risk of oesophageal or gastric adenocarcinoma. Patients: Persons registered in the general practitioners research database in the UK and aged 40–84 years during the period 1994–2001. Methods: Population based nested case control study. Multivariable unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CI). Results: In 4 340 207 person years of follow up, 287 patients with oesophageal adenocarcinoma, 195 with gastric cardia adenocarcinoma, and 327 with gastric non-cardia adenocarcinoma were identified, and 10 000 control persons were randomly sampled. “Oesophageal” indication for long term acid suppression (that is, reflux symptoms, oesophagitis, Barrett’s oesophagus, or hiatal hernia) rendered a fivefold increased risk of oesophageal adenocarcinoma (odds ratio (OR) 5.42 (95% confidence interval (CI) 3.13–9.39)) while no association was observed among users with a group of other indications, including peptic ulcer and “gastroduodenal symptoms” (that is, gastritis, dyspepsia, indigestion, and epigastric pain) (OR 1.74 (95% CI 0.90–3.34)). “Peptic ulcer” indication (that is, gastric ulcer, duodenal ulcer, or unspecified peptic ulcer) was associated with a greater than fourfold increased risk of gastric non-cardia adenocarcinoma among long term users (OR 4.66 (95% CI 2.42–8.97)) but no such association was found in those treated for a group of other indications (that is, “oesophageal” or “gastroduodenal symptoms”) (OR 1.18 (95% CI 0.60–2.32)). Conclusions: Long term pharmacological gastric acid suppression is a marker of increased risk of oesophageal and gastric adenocarcinoma. However, these associations are most likely explained by the underlying treatment indication being a risk factor for the cancer rather than an independent harmful effect of these agents per se.