title: Proton pump inhibitors on pancreatic cancer risk and survival.
abstract: Hypergastrinemia may promote the development and progression of pancreatic cancer. Proton pump inhibitor (PPI) therapy is known to cause hypergastrinemia. We sought to determine the association between PPI therapy and the risk of developing pancreatic cancer as well as survival following pancreatic cancer diagnosis.
  
  
  
  We conducted a nested case-control study and a retrospective cohort study in The Health Improvement Network (THIN), a medical records database representative of the UK population. In the case-control study, each patient with incident pancreatic cancer was matched with up to four controls based on age, sex, practice site and both duration and calendar time of follow-up using incidence density sampling. The odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer risk associated with PPI use were estimated using multivariable conditional logistic regression. The retrospective cohort study compared the survival of pancreatic cancer patients according to their PPI exposure at the time of diagnosis. The effect of PPI use on pancreatic cancer survival was assessed using a multivariable Cox regression analysis.
  
  
  
  The case-control study included 4113 cases and 16,072 matched controls. PPI use was more prevalent in cases than controls (53% vs. 26% active users). Adjusting for diabetes, smoking, alcohol use and BMI, PPI users including both former users and active users with longer cumulative PPI use had a higher risk of pancreatic cancer compared to non-users. When assessing survival following pancreatic cancer diagnosis, only short-term, active users had a modest decrease in survival.
  
  
  
  Long-term PPI therapy may be associated with pancreatic cancer risk. While PPI users recently started on treatment had a slightly worse survival, this result likely is from reverse causation.
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: malcolmdkearns@gmail.com.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Kearns
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Tel Aviv University, Tel Aviv, Israel. Electronic address: bben217@gmail.com.
authors.forename: Ben
authors.initials: B
authors.lastname: Boursi
authors.affiliation: Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: yangy@mail.med.upenn.edu.
authors.forename: Yu-Xiao
authors.initials: YX
authors.lastname: Yang
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D054328:Proton Pump Inhibitors
keywords: Pancreatic cancer; Proton pump inhibitors; Risk; Survival