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Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK
  1. L A García Rodríguez1,
  2. J Lagergren2,
  3. M Lindblad2
  1. 1Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain
  2. 2Unit of Oesophageal and Gastric Research, Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
  1. Correspondence to:
    MrM Lindblad
    Department of Surgery, P9: 03, Karolinska University Hospital, SE-171 76 Stockholm, Sweden; mats.lindblad{at}


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

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