Circulating fibroblast growth factor-23 is associated with increased risk for metachronous colorectal adenoma

Background: Fibroblast growth factor-23 (FGF-23) is a phosphaturic peptide and a key component of an endocrine feedback loop along with the hormonal vitamin D metabolite 1,25(OH) ₂ D. Vitamin D has been shown to be inversely related to colorectal neoplasia; therefore, we hypothesized that the effect of FGF-23 on vitamin D metabolite concentrations could have implications for the risk of colorectal neoplasia. Materials and Methods: The purpose of this study was to prospectively evaluate the association between circulating concentrations of FGF-23 and the risk of metachronous (recurrent) colorectal adenomas. FGF-23 levels were assessed in 100 male and female participants from the Ursodeoxycholic Acid Trial, 50 of whom had a metachronous colorectal adenoma and 50 who did not. Results: Compared to the lowest tertile of FGF-23, the adjusted odds ratios (95% CIs) for the second and third tertiles were 2.80 (0.94 to 8.31) and 3.41 (1.09 to 10.67), respectively (P-trend=.03). In a linear regression model, there was also a statistically significant inverse relationship between FGF-23 and 1,25(OH) ₂ D (β-coefficient=-1. 2; P=.001). In contrast, no statistically significant trend was observed between FGF-23 and 25(OH)D concentrations (β-coefficient=0.55; P=.10). Conclusions: The current work presents novel preliminary evidence of a relationship between FGF-23 and the risk for colorectal neoplasia. FGF-23 activity may be mediated through biologic effects on individual serum and colonic 1,25(OH) ₂ D levels, or it may be independent from the vitamin D pathway. Further studies in larger populations are necessary for confirmation and expansion of these hypothesis-generating results.