Circulating Fibroblast Growth Factor-21 and Risk of Metachronous Colorectal Adenoma

Purpose: Prior work has shown that higher circulating concentrations of fibroblast growth factor-21 (FGF-21) are associated with an increased likelihood of developing colorectal cancer. We conducted a prospective study to assess the relationship between circulating FGF-21 and odds of developing early neoplastic lesions in the colorectum. Methods: A total of 94 study participants were included from the ursodeoxycholic acid (UDCA) trial, a phase III, randomized, double-blind, placebo-controlled clinical trial of the effect of 8–10 mg/kg of body weight UDCA vs. placebo. Logistic regression analyses were conducted to evaluate the association between baseline FGF-21 concentrations and odds of developing a metachronous adenoma. Results: Of the characteristics compared across tertiles of FGF-21 concentrations, including age, race, sex, BMI, and other variables, only a previous personal history of colorectal polyps prior to entry into the UDCA trial was statistically significantly related to FGF-21 levels, with a proportion of 26.7%, 56.7%, and 50.0% across the first, second, and third tertiles, respectively (p < 0.05). Higher circulating concentrations of FGF-21 were statistically significantly associated with greater odds of developing a metachronous colorectal adenoma. After adjusting for potential confounders and when compared with the lowest tertile of FGF-21, the adjusted ORs (95% CIs) for metachronous colorectal adenoma in the second and third tertiles were 4.72 (95% CI, 1.42–15.72) and 3.82 (95% CI, 1.15–12.68), respectively (p trend < 0.05). Conclusion: Our results reveal for the first time that, in addition to a recently discovered association with colorectal cancer, circulating FGF-21 concentrations are significantly and directly associated with odds of developing metachronous colorectal adenoma.