The Impact of Diet‐Induced Weight Loss on Biomarkers for Colorectal Cancer: An Exploratory Study (INTERCEPT)

OBJECTIVE: The aim of this study was to explore the potential effects of diet‐induced weight loss on molecular biomarkers of colorectal cancer risk in serum and colorectal tissue. METHODS: This single‐arm exploratory study included 20 adults with BMI ≥ 30 kg/m(2) completing an 8‐week, complete, low‐energy liquid diet. Pre‐ and postintervention anthropometric measurements, fasting blood draws, and endoscopic examinations to procure colorectal biopsies were performed. Fasting insulin, glucose, insulinlike growth factor 1 (IGF‐1), C‐reactive protein (CRP), and blood lipids were measured in serum, and tissue markers of apoptosis (M30), colonocyte proliferation (Ki‐67), and insulin signaling (phospho‐mTOR) were assessed using immunohistochemical staining. RESULTS: Participants achieved substantial weight loss (mean = 13.56%). Mean concentrations of insulin, glucose, and cholesterol were significantly reduced (P < 0.05), but IGF‐1 and CRP were not. Colorectal tissue expression of Ki‐67 was significantly reduced (preintervention mean score = 7, postintervention mean score = 3.9, mean % change −43.8; P = 0.027). There were no significant changes in M30 or phospho‐mTOR. CONCLUSIONS: Weight loss in individuals with obesity was associated with improvements in insulin sensitivity and blood lipid profiles and a significant reduction in tissue Ki‐67 expression. This is one of the first studies to demonstrate potential cancer‐relevant changes in colorectal tissue following weight loss achieved through diet.