Exposure to proton pump inhibitors and risk of pancreatic cancer: a meta-analysis

ABSTRACT

Objectives: To estimate the pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors.

Methods: The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses.

Results: One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. PPI exposure was associated with pancreatic cancer risk (OR = 1.75, 95%CI = 1.12–2.72, I² = 99%); confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose of PPI exposure. Rabeprazole had a singular significant association with pancreatic cancer (OR = 5.40, 95%CI = 1.98–14.703, I² = 87.9%).

Conclusion: The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses.

KEYWORDS:

• Risk
• pancreatic cancer
• proton pump inhibitors
• meta-analysis

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Author contributions

Concept: I Abraham, N Alkhushaym, A McBride and M Oh. Design: I Abraham, N Alkhushaym, AR Almutairi and M Oh. Data retrieval: N Alkhushaym, A Althagafi, SB Fallatah and JR Martin. Analysis: N Alkhushaym, AR Almutairi and M Oh. Interpretation of data: I Abraham, N Alkhushaym, AR Almutairi, HM Babiker, JR Martin, A McBride and M Oh. Drafting of manuscript: I Abraham and N Alkhushaym. Revising of manuscript for intellectual content: AR Almutairi, A Althagafi, HM Babiker, SB Fallatah, JR Martin, A McBride and M Oh. Final approval of manuscript: I Abraham, N Alkhushaym, AR Almutairi, A Althagafi, HM Babiker, SB Fallatah, JR Martin, A McBride and M Oh. All authors agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was not funded.