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

Mol Carcinog. 2017 Sep;56(9):2127-2134. doi: 10.1002/mc.22669. Epub 2017 May 24.

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.

Keywords: clinical trial; colorectal neoplasms; insulin-like growth factor 1; milk.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / blood*
  • Adult
  • Aged
  • Animals
  • Biomarkers / blood*
  • Calcium, Dietary / pharmacology*
  • Colorectal Neoplasms / blood*
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Middle Aged
  • Milk

Substances

  • Biomarkers
  • Calcium, Dietary
  • IGF1 protein, human
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I