Acid-suppressive medications and risk of colorectal cancer: results from three large prospective cohort studies

Ana Babic,Edward L Giovannucci,Vicente Morales-Oyarvide,Andrew T Chan,Shuji Ogino,Meir J Stampfer,Natalia Khalaf,Charles S Fuchs,Chen Yuan,Brian M Wolpin,Paul Lochhead,Hamed Khalili,Kana Wu,Xuehong Zhang,Kimmie Ng

doi:10.1038/s41416-020-0939-y

Abstract

BackgroundDespite several plausible biological mechanisms linking proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) with colorectal tumorigenesis, their association with risk of colorectal cancer (CRC) has not been adequately assessed in prospective epidemiological studies.MethodsWe evaluated the association of acid-suppressive medication use with CRC risk among 175,871 (PPI) and 208,831 (H2RA) participants from three large prospective cohort studies. Medication use was assessed at baseline and updated biennially. The association was evaluated using multivariate Cox proportional hazards regression models.ResultsThere was no significant association between baseline PPI use (hazard ratio (HR) = 0.89, 95% confidence interval (CI), 0.71–1.12) or PPI use after a lag of 8–10 years (HR = 1.12, 95% CI, 0.78–1.59) with CRC risk. We observed no significant association between H2RA use after a lag of 8–10 years and CRC risk (HR = 1.02, 95% CI, 0.81–1.28), while risk was lower for participants with baseline H2RA use (HR = 0.76, 95% CI, 0.60–0.95). Duration of PPI use or H2RA use was not associated with CRC risk (P-trend = 0.21 and 0.95, respectively).ConclusionsAmong participants from three large prospective cohorts, use of PPI or H2RA was not associated with higher risk of colorectal cancer.

Highlights

Despite several plausible biological mechanisms linking proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) with colorectal tumorigenesis, their association with risk of colorectal cancer (CRC) has not been adequately assessed in prospective epidemiological studies
There was no significant association between baseline use of PPI and risk of colorectal cancer (HR = 0.89, 95% CI, 0.71–1.12), while current PPI use was associated with decreased risk (HR = 0.82, 95% CI, 0.68–0.98) (Table 3)
In this pooled analysis of three large prospective US cohorts, we found no evidence of overall significant association between use of PPI or H2RA medications and risk of colorectal cancer

Summary

Introduction

Despite several plausible biological mechanisms linking proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) with colorectal tumorigenesis, their association with risk of colorectal cancer (CRC) has not been adequately assessed in prospective epidemiological studies. METHODS: We evaluated the association of acid-suppressive medication use with CRC risk among 175,871 (PPI) and 208,831 (H2RA) participants from three large prospective cohort studies. Acid-suppressive medications, including proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs), are among the most widely used medications in the United States.[1]. These are indicated for the treatment of upper gastrointestinal acid-related disorders, including gastrointestinal reflux disease and peptic ulcer disease,[2] but lack of adherence to prescription guidelines, as well as over-the-counter availability, have led to their increasing overuse.[3]. Several recent studies revealed large differences in microbiota composition between PPI users and non-users.[12,13,14] the relationship between colorectal cancer and the gut microbiota is not yet well understood, several studies strongly implicate specific bacterial species in the development of colorectal tumours.[15,16] Fusobacterium nucleatum, a Gram-negative anaerobic commensal associated with increased colorectal cancer risk,[17,18] shows in vitro sensitivity to lansoprazole and omeprazole, the two most commonly used PPIs.[19,20]

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Conclusion