Circulating insulin-like growth factor-related biomarkers: Correlates and responses to calcium supplementation in colorectal adenoma patients

• Type of Material: Article
• Authors: Caroline Y. Um, Emory University; Veronika Fedirko, Emory University; W Dana Flanders, Emory University; Roberd M Bostick, Emory University; Christine Hoeflich, Ligandis GbR; Elisa Wirthgen, Ligandis GbR
• Language: English
• Date: 2017-09-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/mc.22669
• Title of Journal or Parent Work: Molecular Carcinogenesis
• ISSN: 0899-1987
• Volume: 56
• Issue: 9
• Start Page: 2127
• End Page: 2134
• Grant/Funding Information: Original trial: NIH grant R01 CA51932 (to Roberd M. Bostick) IGF-1 and IGFBP-3 analysis: Emory University Laney Graduate School Professional Development Funds (to Caroline Y. Um) and the Franklin Foundation (to Roberd M. Bostick)
• Keywords: insulin-like growth factor 1; CANCER-RISK; Life Sciences & Biomedicine; FACTOR BINDING-PROTEIN-3 CONCENTRATIONS; CLINICAL-TRIAL; milk; Oncology; DIETARY CALCIUM; DAIRY-PRODUCTS; POSTMENOPAUSAL WOMEN; clinical trial; Biochemistry & Molecular Biology; COLONIC EPITHELIUM; EPITHELIAL-CELL PROLIFERATION; Science & Technology; IGF-BINDING PROTEIN-3; colorectal neoplasms; FACTOR-I
• Research Categories: Biology, Genetics; Health Sciences, Nutrition

Abstract

Circulating insulin-like growth factor 1 (IGF-1) may be directly associated with colorectal cancer risk, and IGF binding protein 3 (IGFBP-3) is one of the most abundantly expressed binding proteins in various cancers. Calcium intakes, primarily from food, have been directly associated with circulating IGF-1, but whether supplemental calcium affects IGF-1 and IGFBP-3 is unknown. We tested the effects of 1.0 and 2.0 g of supplemental elemental calcium daily on circulating IGF-1 and IGFBP-3 concentrations in colorectal adenoma patients in a randomized, double-blinded, placebo-controlled clinical trial (n = 193). IGF-1 and IGFBP-3 were quantified using enzyme-linked immunoassay and quantitative Western ligand blot, respectively. We also assessed cross-sectional associations of these biomarkers with participants’ baseline characteristics. We found no appreciable effect of calcium relative to placebo on circulating IGF-1, IGFBP-3, or the IGF-1:IGFBP-3 molar ratio. Mean IGF-1 concentrations were 11.1% higher in those with greater milk intakes (P = 0.05). Mean IGF-1 and IGFBP-3 concentrations were, respectively, 18.0% (P = 0.003) and 16.5% (P = 0.01) higher in men and were monotonically lower with increasing age (both P = 0.01). IGFBP-3 was 17.7% higher among those with higher relative to no alcohol consumption (P = 0.04). While these results support previous findings that IGF-1 concentrations are higher with greater milk intakes, and IGF-1 and IGFBP-3 concentrations differ according to sex and age, they provide no evidence to suggest that supplemental calcium appreciably affects circulating IGF-1, IGFBP-3, or the IGF-1:IGFBP-3 molar ratio in sporadic colorectal adenoma patients.