High-risk colorectal adenomas and serum insulin-like growth factors

Abstract

Abstract Background This study investigated the hypothesis that circulating levels of insulin-like growth factor (IGF) I and its main binding protein (IGFBP-3) predict for the presence of colorectal adenomas, surrogate markers of colorectal cancer risk. Methods Within the Flexi-Scope Trial (healthy volunteers aged 55–64 years), at one study centre, IGF-I and IGFBP-3 levels in serum samples collected prospectively from 442 attendants were measured. Of these, 100 individuals underwent a complete screening colonoscopy. There were 47 normal examinations, while in 11 examinations low-risk adenomas and in 42 examinations high-risk adenomas were identified. Estimates of relative risk (RR) for the adenomatous stages were calculated by means of unconditional logistic regression, adjusting for known risk factors. Results Mean serum IGF-I and IGFBP-3 levels were similar in individuals with a normal colonoscopy finding and in those with low-risk adenomas. By contrast, the mean(s.d.) serum IGF-I level was increased (190(53) versus 169(54) µg/l; P = 0·06) and the serum IGFBP-3 concentration was significantly decreased (3·22(0·60) versus 3·47(0·62) mg/l; P = 0·05) in individuals with high-risk adenomas compared with levels in those with normal colonoscopy and low-risk adenomas combined. Levels were unaffected by removal of the adenomas. With high-risk adenoma as the dependent factor, regression models demonstrated a significant positive association with IGF-I after controlling for IGFBP-3 (RR per one standard deviation (1s.d.) change 4·39 (95 per cent confidence interval (c.i.) 1·31–14·7); P = 0·02) and, independently, an inverse association with IGFBP-3 after adjustment for IGF-I (RR per 1s.d. change 0·41 (95 per cent c.i. 0·20–0·82); P = 0·01). Conclusion These findings suggest that circulating IGF-I and IGFBP-3 levels are related to future colorectal cancer risk and, specifically, may predict adenoma progression.