Abstract 1758: Circulating insulin-like growth factors: Correlates and responses to calcium supplementation in colorectal adenoma patients

Abstract

Abstract Insulin-like growth factor 1 (IGF-1) and its binding proteins are an important part of the IGF/growth hormone axis needed for normal growth and organ function. IGF-1 signaling has also been implicated in tumorigenesis with higher circulating levels of IGF-1 and the molar ratio of IGF-1 to IGF binding protein 3 (IGFBP-3) being directly associated with colorectal, breast, and prostate cancers, as well as with colorectal adenomas. IGF binding protein 2 (IGFBP-2) also appears to be overexpressed in colorectal and lung cancers and leukemias. Limited evidence suggests that various dietary and lifestyle factors may influence circulating levels of IGF-1, IGFBP-2, and IGFBP-3. Among these factors, calcium has been statistically significantly associated with IGF-1, IGFBP-2, and IGFBP-3, but its effects on them have not been tested in a clinical trial. To investigate the effects of supplemental calcium (1.0 or 2.0 g/day) on serum levels of IGF-1, IGFBP-2, and IGFBP-3, we analyzed samples from a randomized, double-blinded, placebo-controlled, dose-response clinical trial of patients with previous sporadic, colorectal adenoma. We also investigated associations of various risk factors with the growth factors at baseline. IGF-1 was measured using an enzyme-linked immunosorbent assay, and IGFBP-2 and IGFBP-3 were measured using quantitative Western ligand blot assays. We found no appreciable effects of calcium over the 4-month treatment period on IGF-1, IGFBP-2, and IGFBP-3. At baseline, lower levels of IGF-1 and IGFBP-3 were associated with being female (P = 0.02 and 0.01, respectively) or older (P = 0.02 and 0.02, respectively); the IGF-1/IGFBP-3 molar ratio was inversely associated with body mass index (BMI) (P = 0.04); and IGFBP-2 was directly associated with age (P = 0.002) but inversely associated with BMI (P < 0.0001). We calculated residuals of non-fat milk intake as a novel method of examining the non-calcium, non-fat component of milk, modeled after the energy adjustment residual method. These residuals were inversely associated with IGFBP-2 (P = 0.05) and directly associated with the IGF-1/IGFBP-3 molar ratio (P = 0.11). Overall, our results do not support that calcium supplementation can modulate circulating levels of IGF-1, IGFBP-2, or IGFBP-3 among patients with previous colorectal adenoma. However, our findings do suggest potential associations of these growth factors with established risk factors for colorectal cancer (age [inversely associated with IGF-1 and IGFBP-3, directly associated with IGFBP-2] and adiposity [inversely associated with IGFBP-2 and the IGF-1/IGFBP-3 molar ratio]). Finally, our results provide new evidence of potential associations of IGF-1, IGFBP-2, and IGFBP-3 with milk intake independent of its calcium and fat content. Citation Format: Caroline Um, Veronika Fedirko, Christine Höflich, W Dana Flanders, Roberd M. Bostick. Circulating insulin-like growth factors: Correlates and responses to calcium supplementation in colorectal adenoma patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1758.