Abstract B36: Circulating FGF-23 is associated with metachronous colorectal adenomas

Fibroblast growth factor-23 (FGF-23) is a phosphaturic peptide and a key component of an endocrine feedback loop with the hormonal vitamin D metabolite 1,25(OH)2D. It is both induced by and represses the synthesis of 1,25(OH)2D in a concerted effort to maintain both calcium and phosphate homeostasis. Vitamin D has been shown to be inversely related to colorectal neoplasia; therefore, we hypothesized that the effect of FGF-23 on 1,25(OH)2D concentrations could have implications for the risk of colorectal neoplasia. The purpose of this study was to prospectively evaluate the association between circulating concentrations of FGF-23 and odds of metachronous (recurrent) colorectal adenomas, the precursors to colorectal cancer. 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. Compared to the lowest tertile of FGF-23, the adjusted ORs (95% CIs) for the second and third tertiles were 2.80 (0.94-8.31) and 3.41 (1.09-10.67), respectively; a significant trend was shown for the relationship between FGF-23 concentration and odds for metachronous adenoma (p=0.03). In addition, there was a statistically significant inverse relationship between FGF-23 and 1,25(OH)2D, with those in the highest tertile of circulating 1,25(OH)2D having the lowest concentrations of FGF-23. Levels of FGF-23 were 81.4 + 36.6 RU/ml, 75.0 + 34.5 RU/ml, 55.7 + 15.8 RU/ml for low, medium, and high tertiles of 1,25(OH)2D, respectively (p-trend=0.001). In contrast, no statistically significant trend was observed between FGF-23 and 25(OH)D concentrations, with FGF-23 levels of 66.4 + 223.4 RU/ml, 69.1 + 38.6 RU/ml, and 76.1 + 40.7 RU/ml among participants who were vitamin D insufficient ( 20 ng/ml and 30 ng/ml); p-trend=0.28. This work provides novel evidence of an association between FGF-23 and risk for colorectal neoplasia, and the results support an important role for FGF-23 as a potential risk biomarker of early colorectal carcinogenesis. The effects of FGF-23 may be mediated through biologic effects on individual 1,25(OH)2D levels. Further studies in larger populations are necessary for confirmation of these results. Citation Information: Cancer Prev Res 2010;3(12 Suppl):B36.