Abstract 1888: Calcium, magnesium, and vitamin D metabolites in colorectal adenoma prevention

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA In addition to the synergistic interaction between calcium and vitamin D observed in many previous studies, a recent study found that magnesium may also modify the association between serum 25-hydroxyvitamin D (25D) and risk colorectal cancer mortality. However, the study was unable to include the biologically active form of vitamin D, 1α,25-dihydroxyvitamin (1,25D), a critical component of calcium homeostasis. Both 1,25D and its precursor metabolite 25D are associated with increased risk of colorectal neoplasia when circulating concentrations are low. Furthermore, no study has investigated whether magnesium may also modify the association between serum vitamin D and risk of colorectal adenoma recurrence. We therefore conducted logistic regression analysis to evaluate the relationship between circulating vitamin D metabolites concentrations and risk of colorectal adenoma recurrence stratified by intake tertiles of magnesium or calcium, among 878 participants from the ursodeoxycholic acid randomized trial for colorectal adenoma prevention. Tertiles were created for all continuous exposure variables and all models were mutually adjusted for either magnesium or calcium, respectively. Although circulating 25D levels were not significantly associated with risk, those with 1,25D levels within the middle tertile were at significantly reduced risk of adenoma recurrence (OR = 0.68, 95% CI: 0.48-0.95). In stratified analysis by tertile of magnesium or calcium intake, we found higher 1,25D concentrations were associated with reduced risks of adenoma recurrence only for those with mean magnesium intake around the Recommended Dietary Allowance (RDA; i.e. 319 mg/day), particularly for proximal colorectal adenoma recurrence, with an OR of 0.48 (95% CI: 2.25-0.89) for the highest tertile of 1,25D compared to the lowest (p for trend, 0.02). Also, we found circulating 1,25D concentrations significantly interacted with intake of calcium in relation to risk of proximal colorectal adenoma recurrence (p for interaction, 0.01); and the inverse association between 1,25D and risk may primarily appeared in those who had intake of calcium close to or above Dietary Reference Intake (DRI) level (i.e. 1000 mg/day). No statistically significant interactions were observed for circulating 25D concentrations. Few studies have evaluated the role of 1,25D in colorectal adenoma recurrence or interactions with intake of calcium, and this is the first to examine the interaction between 1,25D with intake of magnesium. These results support the importance of interactions between calcium and magnesium homeostasis with the vitamin D endocrine system in the development of colorectal neoplasia; however, continued work, particularly large-scale studies, is necessary to replicate the finding and understand the cellular mechanism driving these population-level associations as well as applications to colorectal neoplasia prevention. Citation Format: Elizabeth A. Hibler, Peter W. Jurutka, Qi Dai, Christine L. Sardo Molmenti, Elizabeth T. Jacobs. Calcium, magnesium, and vitamin D metabolites in colorectal adenoma prevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1888. doi:10.1158/1538-7445.AM2015-1888