Calcium Intake and Risk of Colorectal Cancer in the NIH-AARP Diet and Health Study

Importance  Calcium intake is associated with a reduced risk of colorectal cancer (CRC), although it remains unclear whether this association varies by calcium source or tumor site. Moreover, there are disparities in calcium intake by race and ethnicity, but the impact of low calcium consumption on CRC risk in specific racial and ethnic populations is unclear.

Objective  To investigate the association between calcium intake and CRC risk, considering the source of calcium and tumor site and across racial and ethnic groups.

Design, Setting, and Participants  This cohort study analyzed data from the National Institutes of Health–AARP Diet and Health Study. Participants were aged 50 to 71 years at baseline (October 1995 to May 1996), had self-reported good health and neither extremely high nor low caloric or calcium intake, and were followed up until the date of their first primary cancer diagnosis, death, loss to follow-up, or end of follow-up (December 31, 2018). Data were analyzed from April 2022 to April 2024.

Exposure  Calcium intake was estimated from dietary sources (dairy and nondairy), supplements, and total intake.

Main Outcomes and Measures  The primary outcome was CRC incidence. Multivariable-adjusted Cox proportional hazards regression models estimated hazard ratios (HRs) and 95% CIs using the lowest sex-specific quintile of calcium intake as the reference.

Results  Among 471 396 participants who were cancer-free at baseline, mean (SD) baseline age was 62.0 (5.4) years and 59.5% were male. During 7 339 055 person-years of follow-up (median, 18.4 years [IQR, 9.2-22.5 years]), 10 618 first primary CRC cases were identified. Mean (SD) total calcium intake for the lowest quintile (Q1) was 401 mg/d (104 mg/d) for females and 407 mg/d (95 mg/d) for males and for the highest quintile (Q5) was 2056 mg/d (412 mg/d) for females and 1773 mg/d (444 mg/d) for males. Dairy, nondairy, and supplemental sources contributed a mean (SD) of 42.1% (43.5%), 34.2% (24.5%), and 23.7% (38.3%) of total calcium intake, respectively. Higher total calcium intake (Q5 vs Q1) was associated with a lower risk of CRC (hazard ratio , 0.71; 95% CI, 0.65-0.78; P < .001 for trend), with consistent results across calcium sources and tumor sites. Among non-Hispanic Black participants, the mean (SD) calcium intake was 382 mg/d (108 mg/d) for Q1 and 1916 mg/d (466 mg/d) for Q5, with no association of total calcium intake with CRC risk (Q5 vs Q1: HR, 0.60; 95% CI, 0.32-1.13; P = .12 for trend); there was no evidence of effect measure differences by race and ethnicity.

Conclusions and RelevanceIn this cohort study, higher calcium intake was consistently associated with reduced CRC risk across tumor sites and sources of calcium. Increasing calcium intake, especially among groups with lower consumption, may be associated with reductions in avoidable differences in CRC risk.

Accepted for Publication: December 17, 2024.

Published: February 17, 2025. doi:10.1001/jamanetworkopen.2024.60283

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2025 Zouiouich S et al. JAMA Network Open.

Corresponding Author: Erikka Loftfield, PhD, MPH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Rockville, MD 20850 (erikka.loftfield@nih.gov).

Author Contributions: Drs Zouiouich and Loftfield had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Sinha and Loftfield were co–senior authors and contributed equally to the work.

Concept and design: Zouiouich, Sinha, Loftfield.

Acquisition, analysis, or interpretation of data: Zouiouich, Wahl, Liao, Hong, Loftfield.

Drafting of the manuscript: Zouiouich, Sinha, Loftfield.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Zouiouich, Wahl, Hong, Sinha.

Obtained funding: Sinha.

Administrative, technical, or material support: Liao.

Supervision: Zouiouich, Sinha, Loftfield.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by the Intramural Research Program of the National Cancer Institute (NCI) at the National Institutes of Health (NIH).

Role of the Funder/Sponsor: The NCI and NIH had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed herein are solely those of the authors and do not necessarily reflect those of the Florida Cancer Data System or Florida Department of Health. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions.

Data Sharing Statement: See Supplement 2.

Additional Contributions: Sigurd Hermansen, MA, and Kerry Grace Morrissey, MPH, Westat, aided in study outcomes ascertainment and management for the NIH-AARP Diet and Health Study, and Leslie Carroll, BS, Information Management Services, provided data support and analysis. They were compensated for this work.

Additional Information: Cancer incidence data from the Atlanta metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta. Cancer incidence data from California were collected by the California Cancer Registry, California Department of Public Health’s Cancer Surveillance and Research Branch, Sacramento. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, Lansing. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (Miami) under contract with the Florida Department of Health, Tallahassee. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Health Sciences Center School of Public Health, New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Rutgers Cancer Institute of New Jersey, New Brunswick. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry, Raleigh. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services, Phoenix. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin. Cancer incidence data from Nevada were collected by the Nevada Central Cancer Registry, Division of Public and Behavioral Health, State of Nevada Department of Health and Human Services, Carson City.