(AA) Proton Pump Inhibitors and Colorectal Cancer Mortality: A Population-Based Nationwide Cohort Study

Friday, August 26, 2022

8:00 AM – 6:00 PM CEST

Location: Hall E South

Publication Number: 317

Presenting Author(s)

Jannik Wheler
– Department of clinical epidemiology, Aarhus University & Aarhus University Hospital, Aarhus N, Midtjylland, Denmark

Co-Author(s)

Deirdre Cronin-Fenton
– Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark, Denmark
Anders Kjærsgaard
– Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark, Denmark
Timothy Lash
– Department of Epidemiology, Emory University, Atlanta, GA, United States
Rune Erichsen
– Department of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, Aarhus, Denmark, Denmark
Veronika Fedirko
– Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA, United States

Background: Proton pump inhibitors (PPIs) are widely prescribed to treat gastroesophageal reflux. However, PPIs may impede the effectiveness of cytotoxic drugs due to alkalinization of the gastric environment. Recent studies suggest that PPI use is associated with decreased overall and disease-free survival among colorectal cancer (CRC) patients treated with chemotherapy.

Objectives: To determine the association of PPI use (pre- and post-diagnostic) with mortality overall and according to the receipt of chemotherapy among CRC patients.

Methods: We used Danish nationwide population-based and medical registries to conduct a cohort study of individuals diagnosed with stage I-III CRC (2001–2011). We ascertained information on PPI use from the Danish National Prescription Registry. We defined PPI use as the redemption of >=1 PPI prescription up to 90 days before the date of CRC diagnosis (pre-diagnostic use) starting follow-up at the date of CRC diagnosis. We defined post-diagnostic PPI use as a time-varying exposure to >=1 PPI prescription lagged by one year, starting follow-up from 6 months after CRC diagnosis (to approximate the end of chemotherapy). We followed patients to date of death, emigration, or 31st December 2012. We used Cox regression to compute all-cause and cancer-specific hazards ratios (HR) and associated 95% confidence intervals (95%CIs) of mortality adjusting for potential confounders and stratifying by the receipt of chemotherapy.

Results: Among 21,152 CRC patients, 3,104 and 3,469 were pre- and post-diagnostic PPI users, respectively. Overall, 53% of the study population were men, 65% had colon cancer and 35% had rectal cancer. Pre-diagnostic and post-diagnostic PPI use were associated with elevated all-cause (HR=1.09, 95% CI=1.02–1.16 and HR=1.38, 95% CI=1.31-1.46) and cancer-specific mortality (HR=1.05, 95% CI=0.95–1.15 and 1.38, 95% CI=1.28–1.49), respectively. We observed similar findings when stratifying by the receipt of chemotherapy.

Conclusions: Pre- and post-diagnostic use of PPIs was associated with increased overall and cancer-specific mortality after CRC diagnosis, irrespective of the receipt of chemotherapy. Our findings emphasize the need for future studies on the safety of using PPI when diagnosed with CRC.