#GUT Blog: Proton pump inhibitors and risk of colorectal cancer: population-based cohort study

Professor El-Omar has chosen Dr Devin Abrahami and Dr Laurent Azoulay to do the next #GUTBlog. Dr Abrahami is a postdoctoral fellow in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School. She received her PhD in Pharmacoepidemiology at McGill University. Dr Azoulay is an Associate Professor in the Department of Epidemiology, Biostatistics, and Occupational Health and the Gerald Bronfman Department of Oncology at McGill University.

The #GUTBlog focusses on the latest paper “Proton pump inhibitors and risk of colorectal cancer: population-based cohort study” which was published in paper copy in GUT in January 2022.  Dr Abrahami is the first author on this paper, Dr Azoulay is the senior author.

Dr Devin Abrahami (L) & Dr Laurent Azoulay (R)


Dr Abrahami and Dr Azoulay write:

“Acid suppressant drugs, which include proton pump inhibitors, or PPIs, and histamine-2 receptor antagonists, or H2RAs, are among the most commonly prescribed drugs worldwide. These drugs are used by millions of adults in the United Kingdom (UK) to manage the symptoms of several common gastric conditions, including peptic ulcer disease and gastroesophageal reflux disease. In recent years, however, there has been concern that these drugs are being used inappropriately, in either patients without an underlying indication for use or for increasing durations. This overuse is particularly concerning given the emergence of safety issues potentially associated with the use of PPIs, including infections, kidney issues, and certain cancers, such as colorectal cancer. As colorectal cancer is becoming more common among younger adults, this is a particularly relevant safety question. Thus, we set out to answer the following: is the use of PPIs associated with an increased risk of colorectal cancer?

To answer this safety question, we used data from the UK Clinical Practice Research Datalink, a large, computerized data set with detailed records of patients from primary care physicians. Using this data, we identified a group of over 1.5 million adults who were newly treated with an acid suppressant drug. We followed these patients over time to assess their colorectal cancer risk, using advanced statistical techniques to adjust for differences between the two groups. We quantified the overall risk of colorectal cancer associated with the use of PPIs, compared to the use of H2RAs, and the risk among important subgroups.

Our study found that the overall use of PPIs was not associated with an increased risk of colorectal cancer. However, we found that prolonged PPI use may be associated with a modest increased risk of colorectal cancer when examining duration-response patterns. The risk was particularly high among patients using PPIs in the highest duration of use, corresponding to about four years of treatment.

Given the pervasiveness of PPIs, physicians should closely monitor their patients to regularly reassess their ongoing need for treatment. In addition, regular colorectal cancer screening among long-term PPI users may also be warranted. In light of the risk associated with long-term use, patients who do not have an indication for use should be weaned off their PPI medications.

Overall, this study adds to the growing body of literature on the risk-benefit profile of acid suppressant drugs. While these drugs effectively reduce stomach acid, this study highlights that their use may have some unintended effects, particularly associated with prolonged use.Future work in this area is necessary to confirm our findings and better elucidate the biological role of PPIs in the development of colorectal cancer.”

Dr Devin Abrahami @DevinAbrahami

Dr Laurent Azoulay @LaurentAzoulay0

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