STOMACH

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

L A García Rodríguez¹, J Lagergren², M Lindblad²

¹ Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain
² Unit of Oesophageal and Gastric Research, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden

Correspondence to:
MrM Lindblad
Department of Surgery, P9: 03, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; mats.lindblad{at}karolinska.se

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.

Abbreviations: 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

Keywords: histamine H2 antagonists; proton pump inhibitors; gastric acid suppression; oesophageal adenocarcinoma; gastric cancer

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