Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer

Cancer Causes Control. 2000 Mar;11(3):231-8. doi: 10.1023/a:1008913828105.


Objective: The incidence of esophageal adenocarcinoma has risen rapidly in the past two decades, for unknown reasons. The goal of this analysis was to determine whether gastroesophageal reflux disease (GERD) or the medications used to treat it are associated with an increased risk of esophageal or gastric cancer, using data from a large population-based case-control study.

Methods: Cases were aged 30-79 years, newly diagnosed with esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261), or non-cardia gastric adenocarcinoma (n = 368) in three areas with population-based tumor registries. Controls (n = 695) were chosen by random digit dialing and from Health Care Financing Administration rosters. Data were collected using an in-person structured interview.

Results: History of gastric ulcer was associated with an increased risk of non-cardia gastric adenocarcinoma (OR 2.1, 95% CI 1.4-3.2). Risk of esophageal adenocarcinoma increased with frequency of GERD symptoms; the odds ratio in those reporting daily symptoms was 5.5 (95% CI 3.2-9.3). Ever having used H2 blockers was unassociated with esophageal adenocarcinoma risk (OR 0.9, 95% CI 0.5-1.5). The odds ratio was 1.3 (95% CI 0.6-2.8) in long-term (4 or more years) users, but increased to 2.1 (95% CI 0.8-5.6) when use in the 5 years prior to the interview was disregarded. Risk was also modestly increased among users of antacids. Neither GERD symptoms nor use of H2 blockers or antacids was associated with risk of the other three tumor types.

Conclusions: Individuals with long-standing GERD are at increased risk of esophageal adenocarcinoma, whether or not the symptoms are treated with H2 blockers or antacids.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / epidemiology*
  • Adenocarcinoma / etiology
  • Adult
  • Aged
  • Antacids / therapeutic use
  • Carcinoma, Squamous Cell / epidemiology*
  • Carcinoma, Squamous Cell / etiology
  • Case-Control Studies
  • Esophageal Neoplasms / epidemiology*
  • Esophageal Neoplasms / etiology
  • Female
  • Gastroesophageal Reflux / complications
  • Gastroesophageal Reflux / drug therapy
  • Gastroesophageal Reflux / epidemiology*
  • Histamine H2 Antagonists / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Stomach Neoplasms / epidemiology*
  • Stomach Neoplasms / etiology
  • Stomach Ulcer / complications
  • Washington / epidemiology


  • Antacids
  • Histamine H2 Antagonists