Body mass index, calcium supplementation and risk of colorectal adenomas

• 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
• Journal Title: International Journal of Cancer
• Volume: Volume 144, Number 3
• Publisher: Wiley | 2019-02-01, Pages 448-458
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1002/ijc.31803
• Subjects: Health Sciences, Epidemiology; Health Sciences, Oncology; Health Sciences, Public Health; Health Sciences, Nutrition
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; calcium supplementation; colorectal adenoma; body mass index; clinical trial; Dose-response metaanalysis; Mechanisms linking obesity; Vitamin D; Cancer risk; Bile-acids; Extracellular acids; Colon cancer; Dietary; Prevention; Trial

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.