Epidemiology

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

Abstract

Background

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. Medication use was assessed at baseline and updated biennially. The association was evaluated using multivariate Cox proportional hazards regression models.

Results

There 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).

Conclusions

Among participants from three large prospective cohorts, use of PPI or H2RA was not associated with higher risk of colorectal cancer.

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Acknowledgements

We would like to thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA and WY. The authors assume full responsibility for analyses and interpretation of these data.

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Authors

Contributions

Designed the study: A.B., K.N. Analysed the data: A.B., X.Z., K.N. Interpreted results: A.B., X.Z., V.M.-O., C.Y., N.K., H.K., P.L., A.T.C., S.O., B.M.W., K.W., C.S.F., E.L.G., M.J.S., K.N. Approved the final manuscript version: A.B., X.Z., V.M.-O., C.Y., N.K., H.K., P.L., A.T.C., S.O., B.M.W., K.W., C.S.F., E.L.G., M.J.S., K.N.

Corresponding author

Correspondence to Ana Babic.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Institutional Review Boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and those of participating registries as required. Completion of the baseline questionnaire was considered to imply informed consent.

Data availability

Information on obtaining access to NHS, NHSII and HPFS data is available at https://www.nurseshealthstudy.org/researchers (email: nhsaccess@channing.harvard.edu) and https://sites.sph.harvard.edu/hpfs/for-collaborators.

Competing interests

The authors declare no competing interests.

Funding information

This work was supported by following research grants from the National Institutes of Health (NIH): UM1 CA167552, UO1 CA176726, UO1 CA186107, P01 CA55075 and P01 CA87969. Additional support from NIH K07 CA222159 to A.B.; NIH K07 CA188126 and American Cancer Society Research Scholar Grant (RSG130476) to X.Z.; NIH R01 CA151993 and R35 CA197735 to S.O.; NIH R01 CA118553 to C.S.F.; Cancer Research UK Grand Challenge OPTIMISTICC Project award to S.O. and K.N.; Crohn’s and Colitis Foundation to P.L., NIH R01 CA205406, DOD CA160344 and Project P Fund to K.N. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funding sources played no role in study design, data collection, data analysis, interpretations of results or manuscript preparation.

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Babic, A., Zhang, X., Morales-Oyarvide, V. et al. Acid-suppressive medications and risk of colorectal cancer: results from three large prospective cohort studies. Br J Cancer 123, 844–851 (2020). https://doi.org/10.1038/s41416-020-0939-y

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