title: High-risk colorectal adenomas and serum insulin-like growth factors.
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) microg/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).
  
  
  CONCLUSIONS
  These findings suggest that circulating IGF-I and IGFBP-3 levels are related to future colorectal cancer risk and, specifically, may predict adenoma progression.
authors.affiliation: Department of Surgery, Cancer Research Campaign Department of Epithelial Biology, Paterson Institute for Cancer Research, Manchester, UK. arenehan@picr.man.ac.uk
authors.forename: A G
authors.initials: AG
authors.lastname: Renehan
authors.forename: J E
authors.initials: JE
authors.lastname: Painter
authors.forename: W S
authors.initials: WS
authors.lastname: Atkin
authors.forename: C S
authors.initials: CS
authors.lastname: Potten
authors.forename: S M
authors.initials: SM
authors.lastname: Shalet
authors.forename: S T
authors.initials: ST
authors.lastname: O'Dwyer
mesh_terms: D000236:Adenoma / Q000097:blood / Q000175:diagnosis*; D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I