• Circulating insulin-like growth factor II and colorectal adenomas.

      Renehan, Andrew G; Painter, John E; O'Halloran, Domhnall J; Atkin, Wendy S; Potten, Christopher S; O'Dwyer, Sarah T; Shalet, Stephen M; Department of Surgery, Christie Hospital National Health Service Trust, Manchester, United Kingdom. (2000-09)
      Circulating insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) may be risk factors for the development of colorectal cancer. On the other hand, IGF-II and IGFBP-2 are overexpressed in colorectal carcinomas. These contrasting backgrounds led us to investigate the relationship between serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 and the presence of colorectal adenomas, known precursors of colorectal carcinoma, in 345 volunteers attending a screening flexible sigmoidoscopy trial (entry criteria: healthy, aged 55-64 yr). The most striking finding was an elevated mean serum IGF-II in individuals with adenomas (n = 52) compared with controls (mean difference, 139 ng/mL; 95% confidence intervals, 82, 196; P < 0.0001). Logistic regression adjusting for confounding factors confirmed the significant association between IGF-II and adenoma occurrence (P < 0.0001) and revealed an additional positive association with serum IGFBP-2 (P < 0.0001). However, there was no association found between either serum IGF-I and/or IGFBP-3 and the presence of adenomas. Additionally, in 31 individuals with adenomas in whom levels were determined pre- and postpolypectomy, there was a significant fall in mean IGF-II (P < 0.001) and IGFBP-2 (P < 0.001) after adenoma removal, but no difference in IGF-II and IGFBP-2 concentrations between repeated samples in 20 individuals without adenomas. Immunohistochemical studies demonstrated IGF-II expression in 83% of all adenomas, which contrasted with absent expression in normal colonic expression and hyperplastic polyps. This study has shown for the first time that serum IGF-II may be a tumor marker in individuals with colorectal adenomas. Further studies are needed to validate these relationships in larger populations, including individuals undergoing colonoscopy.
    • High-risk colorectal adenomas and serum insulin-like growth factors.

      Renehan, Andrew G; Painter, John E; Atkin, W S; Potten, Christopher S; Shalet, Stephen M; O'Dwyer, Sarah T; Department of Surgery, Cancer Research Campaign Department of Epithelial Biology, Paterson Institute for Cancer Research, Manchester, UK. arenehan@picr.man.ac.uk (2001-01)
      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). 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.