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

Background: Gastric acid suppressing drugs (that is, histamine(2) 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 noncardia 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.