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Epidemiology

Long-term use of antihypertensive medications, hypertension and colorectal cancer risk and mortality: a prospective cohort study

Abstract

Background

Hypertension and the use of antihypertensive medications have been intensively investigated in relation to colorectal cancer (CRC). Prior epidemiologic studies have not been able to examine this topic with adequate confounding control and follow-up time, or disentangle the effects of antihypertensive agents and hypertension.

Methods

Eligible participants in the Nurses’ Health Study and Health Professionals Follow-up Study were followed for up to 28 years, with repeat assessments of exposures. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals.

Results

In fully adjusted analyses based on both new-user and prevalent-user designs, there was no association between the use of beta-blockers, calcium-channel blockers, thiazide diuretics, angiotensin-converting enzyme inhibitors, furosemide, other antihypertensive drugs and CRC risk and mortality reached the statistically significant threshold after Bonferroni correction. The results remained similar in sensitivity analyses among participants with hypertension. Before Bonferroni correction, suggestive associations between beta-blocker use and CRC risk and between furosemide use and CRC-specific mortality were observed specifically in analyses using a new-user design. Hypertension was not associated with CRC risk in analyses based on both new-user and prevalent-user designs.

Conclusions

Hypertension and long-term use of major classes of antihypertensive medications are unlikely to be associated with CRC risk and mortality.

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Data availability

Data described in the manuscript may be made available upon application to and approval by the Channing Division of Network Medicine at Brigham and Women’s Hospital, and Harvard T.H. Chan School of Public Health. Further information, including the procedures to obtain and access data from the Nurses’ Health Study and Health Professionals Follow-up Study, is described at https://www.nurseshealthstudy.org/researchers (email: nhsaccess@channing.harvard.edu) and https://sites.sph.harvard.edu/hpfs/for-collaborators/.

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Acknowledgements

The authors thank all participants and staff of the Nurses’ Health Study and Health Professionals Follow-up Study for their contributions to this research. The authors thank the Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School for leading the Nurses’ Health Study. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centers. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, Wyoming. The authors assume full responsibility for the analyses and interpretation of these data.

Funding

Nurses’ Health Study and Health Professionals Follow-up Study was supported by grants UM1 CA186107, U01 CA176726, P01 CA87969, and U01 CA167552 from the National Institutes of Health (NIH). This work was additionally supported by the American Cancer Society Mentored Research Scholar Grant MRSG-17–220–01-NEC and the NIH grant R00 CA215314 (Dr. Song); NIH grants R01 CA137178, R35 CA253185 (Dr. Chan); and a grant from the World Cancer Research Fund (Dr. Giovannucci). Dr. Zhang is supported by Irene M. & Fredrick J. Stare Nutrition Education Fund Doctoral Scholarship and Mayer Fund Doctoral Scholarship. Dr. Chan is a Stuart and Suzanne Steele MGH Research Scholar. The funding sources played no role in the study design, data collection, data analysis and interpretation of the results, or the decisions made in the preparation and submission of the article.

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Authors and Affiliations

Authors

Contributions

Concept and design: YZ, WCW and ELG. Acquisition, analysis or interpretation of the data: YZ. Drafting of the manuscript: YZ. Critical revision of the manuscript for important intellectual content: ELG, WCW, JAM, ATC and MS. Statistical analysis: YZ. Obtained funding: YZ, MS, ATC and ELG. Administrative, technical or material support: ELG and WCW. Supervision: ELG. The authors assume full responsibility for the analyses and interpretation of these data.

Corresponding author

Correspondence to Edward L. Giovannucci.

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Competing interests

Dr. Meyerhardt declares institutional research funding from Boston Biomedical and consulting for Ignyta, Taiho Pharmaceutical, and Cota, outside the submitted work. Dr. Chan declares research funding from Bayer and consulting for Bayer, Pfizer Inc. and Boehringer Ingelheim, outside the submitted work. The remaining authors declare no competing interests.

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The Nurses’ Health Study and Health Professionals Follow-up Study were approved by the Institutional Review Boards of the Brigham and Women’s Hospital and the Harvard T.H. Chan School of Public Health (Boston, MA), and those of participating registries as required. Written informed consent was required to retrieve medical records.

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Zhang, Y., Song, M., Chan, A.T. et al. Long-term use of antihypertensive medications, hypertension and colorectal cancer risk and mortality: a prospective cohort study. Br J Cancer 127, 1974–1982 (2022). https://doi.org/10.1038/s41416-022-01975-4

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