Body mass index, calcium supplementation and risk of colorectal adenomas

• Type of Material: Article
• Authors: Elizabeth L. Barry, Dartmouth College; Jennifer L. Lund, University of North Carolina; Daniel Westreich, University of North Carolina; Leila A. Mott, Dartmouth College; Dennis J. Ahnen, University of Colorado; Gerald J. Beck, Cleveland Clinic; Roberd Bostick, Emory University; Robert S. Bresalier, University of Texas MD Anderson Cancer Center; Carol A. Burke, Cleveland Clinic; Timothy R. Church, University of Minnesota; Judy R. Rees, Dartmouth College; Douglas J. Robertson, Dartmouth College; John A. Baron, University of North Carolina
• Language: English
• Date: 2019-02-01
• Publisher: Wiley
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 UICC.
• Final Published Version (URL): http://dx.doi.org/10.1002/ijc.31803
• Title of Journal or Parent Work: International Journal of Cancer
• Volume: 144
• Issue: 3
• Start Page: 448
• End Page: 458
• Grant/Funding Information: This research was supported by the National Institutes of Health (NIH) grants CA046927 and CA098286 (to JAB) and HD084070 (to DW).
• Keywords: Cancer risk; Oncology; Trial; Extracellular acids; Life Sciences & Biomedicine; Dietary; clinical trial; Science & Technology; body mass index; calcium supplementation; Bile-acids; colorectal adenoma; Vitamin D; Dose-response metaanalysis; Mechanisms linking obesity; Prevention; Colon cancer
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Oncology; Health Sciences, Nutrition; Health Sciences, Public Health

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.