Considerable attention has been focused on long-term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA-damaged cells. The aim of this study is to examine the dose-dependent effect of PPI on periampullary cancers in a national population-based cohort. A nested case-control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A "PPI user" was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow-up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16-1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose-dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long-term PPI use was associated with an increased risk of periampullary cancers in the current population-based study. Physicians must weigh potential risks of long-term maintenance against therapeutic benefit. What's new? Proton pump inhibitor (PPI) medications are a common treatment for gastroesophageal reflux disease and peptic ulcer disease. However, some evidence indicates that long-term use of PPIs might increase cancer risk. This large Taiwanese study found that PPI exposure was indeed slightly linked to an increased risk of periampullary cancers, in a dose-dependent manner. (This was not seen in patients undergoing H. pylori eradication therapy, however.) These results indicate that physicians must weigh the potential risks of long-term maintenance use of PPIs against their therapeutic benefit.

Original languageEnglish
Pages (from-to)1401-1409
Number of pages9
JournalInternational Journal of Cancer
Issue number6
Publication statusPublished - Mar 15 2016


  • H. pylori eradication therapy
  • nested case-control study
  • periampullary cancers
  • proton pump inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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