Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK
- 1Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain
- 2Unit of Oesophageal and Gastric Research, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
- Correspondence to:
Department of Surgery, P9: 03, Karolinska University Hospital, SE-171 76 Stockholm, Sweden;
- Accepted 7 June 2006
- Revised 12 April 2006
- Published Online First 19 June 2006
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.
- BMI, body mass index
- GORD, gastro-oesophageal reflux disease
- GP, general practitioner
- GPRD, general practitioners research database
- H2 blockers, histamine2 receptor antagonists
- OR, odds ratio
- PPI, proton pump inhibitor
- histamine H2 antagonists
- proton pump inhibitors
- gastric acid suppression
- oesophageal adenocarcinoma
- gastric cancer
Published online first 19 June 2006
Conflict of interest: None declared.