Body mass index, calcium supplementation and risk of colorectal adenomas

Elizabeth L. Barry, Jennifer L. Lund, Daniel Westreich, Leila A. Mott, Dennis J. Ahnen, Gerald J. Beck, Roberd M. Bostick, Robert S. Bresalier, Carol A. Burke, Timothy R. Church, Judy R. Rees, Douglas J. Robertson, John A. Baron

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Calcium supplementation (1,200 mg/day) did not significantly reduce colorectal adenomas in our recent randomized, controlled trial (Vitamin D/Calcium Polyp Prevention Study, VCPPS, 2004–2013) in contrast to our previous trial (Calcium Polyp Prevention Study, CPPS, 1988–1996). To reconcile these findings, we identified participant characteristics that differed between the study populations and modified the effect of calcium supplementation on adenomas or high-risk findings (advanced or multiple adenomas). Compared to the CPPS, more participants in the VCPPS were obese (body mass index (BMI) ≥30 kg/m 2 ; 37.5% vs. 24.4%) and fewer had normal BMI (BMI <25 kg/m 2 ; 18.5% vs. 31%). BMI appeared to modify the effect of calcium supplementation on adenomas and especially on high risk-findings: in the VCPPS, there was a 44% reduction in high-risk findings among individuals whose BMI was normal (RR = 0.56, 95% CI = 0.26–1.23), but not among overweight (RR = 1.09, 95% CI = 0.62–1.91) or obese (RR = 1.54, 95% CI = 0.92–2.57) individuals (p interaction = 0.03). Similarly, in the CPPS, there was a 56% reduction in high-risk findings among individuals whose BMI was normal (RR = 0.44, 95% CI = 0.26–0.74), but not among overweight (RR = 0.87, 95% CI = 0.55–1.39) or obese (RR = 1.02, 95% CI = 0.57–1.82) individuals (p interaction = 0.02). Standardization of each trial's findings to the BMI distribution in the other attenuated calcium's protective effect on adenomas in the CPPS but enhanced it in the VCPPS. In conclusion, 1,200 mg/day calcium supplementation may reduce risk of colorectal adenomas among those with normal BMI but not in overweight or obese individuals; and differences in BMI distribution partially account for the apparent difference in calcium efficacy between the two trials.

Original languageEnglish (US)
Pages (from-to)448-458
Number of pages11
JournalInternational Journal of Cancer
Volume144
Issue number3
DOIs
StatePublished - Feb 1 2019

Bibliographical note

Funding Information:
Key words: calcium supplementation, colorectal adenoma, body mass index, clinical trial Abbreviations: CPPS: Calcium Polyp Prevention Study; VCPPS: Vitamin D/Calcium Polyp Prevention Study; BMI: body mass index; RR: relative risk; CI: confidence interval; SD: standard deviation; NSAID: nonsteroidal anti-inflammatory drug; NHW: non-Hispanic white; NHB: non-Hispanic black. Additional Supporting Information may be found in the online version of this article. Conflicts of interest: Dr. Lund receives research support from the PhRMA Foundation to the University of North Carolina at Chapel Hill. Dr. Lund’s spouse is a full-time paid employee of GlaxoSmithKline (which markets calcium supplements). Dr. Westreich is a consultant for Sanofi Pasteur pharmaceutical company. Dr Ahnen serves on the Data and Safety Monitoring Committee for Cancer Prevention Pharmaceuticals, and the Speakers Bureau for Ambry Genetics. Dr. Burke receives research support from Cancer Prevention Pharmaceuticals and Ferring Pharmaceuticals, and she is a consultant for Sucampo Pharmaceuticals, Salix Pharmaceuticals and Aries Pharmaceuticals. Dr. Baron, along with Dartmouth College, holds a use patent for the chemopreventive use of calcium (currently not licensed, formerly licensed by Pfizer). Pfizer provided the study tablets at no cost to the VCCPS. The remaining authors report no potential conflicts of interest. Grant sponsor: National Institutes of Health; Grant numbers: CA046927, CA098286, HD084070 DOI: 10.1002/ijc.31803 History: Received 8 Jun 2018; Accepted 27 Jul 2018; Online 17 Aug 2018 Correspondence to: Elizabeth L. Barry, One Medical Center Drive, Rubin Building 7927, Lebanon, NH 03756, USA, E-mail: elizabeth.l. barry@dartmouth.edu; Tel.: +1-603-653-9932

Keywords

  • body mass index
  • calcium supplementation
  • clinical trial
  • colorectal adenoma

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