Ana Florea1,2, Robin B Harris3, Yann C Klimentidis3, Lindsay N Kohler3,4, Peter W Jurutka5,6, Elizabeth T Jacobs3. 1. Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA. aflorea@arizona.edu. 2. Department of Medicine, Division of Nephrology, College of Medicine, University of Arizona, Tucson, AZ, USA. aflorea@arizona.edu. 3. Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA. 4. Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA. 5. School of Mathematical and Natural Sciences, Arizona State University, Glendale, AZ, USA. 6. Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, USA.
Abstract
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.
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.