Increase in circulating levels of IGF-1 and IGF-1/IGFBP-3 molar ratio over a decade is associated with colorectal adenomatous polyps

Int J Cancer. 2012 Jul 15;131(2):512-7. doi: 10.1002/ijc.26393. Epub 2011 Sep 14.


High levels of circulating insulin-like growth factor-1 (IGF-1) have been associated with increased risk of several cancers. Regarding colorectal cancer, these associations are generally weak. We hypothesized that an increase in IGF-1 over time would be a stronger risk factor for cancer-related outcomes than the actual levels. In this analysis we utilized existing data from the Insulin Resistance and Atherosclerosis Study (IRAS). Circulating IGF-1 levels and molar ratios of IGF-1 to IGF binding protein 3 (IGFBP-3) were measured at three time points, within a 10-year follow-up period. We examined the associations of increase of the two variables with the presence of colorectal adenoma at the end of follow-up among participants with normal glucose tolerance at baseline. This included 143 individuals, from which 24 were diagnosed with adenomatous polyps. Although the mean levels of IGF-1 and IGF-1/IGFBP-3 decline with age, ~ 30% of the participants showed an increase of at least fifteen percent ("ever increase") in one or both of these variables, compared to baseline. We found a positive association between "ever increase" in IGF-1 or IGF-1/IGFBP-3 and the presence of colorectal adenoma: ORs were 3.81 (95% CI: 1.30-10.8) and 2.83 (95% CI: 1.00-8.22), respectively. No association was found when analyzing the actual levels of both variables at any time point. Our data suggest that an increase in circulating IGF-1 or IGF-1/IGFBP-3 may represent a disturbed GH/IGF1 homeostasis, which could favor the development of precancerous lesions such as colorectal adenoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenomatous Polyps / blood*
  • Adenomatous Polyps / pathology
  • Adult
  • Aged
  • Colonic Polyps / blood*
  • Colonic Polyps / pathology
  • Colonoscopy
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / biosynthesis
  • Insulin-Like Growth Factor Binding Protein 3 / blood*
  • Insulin-Like Growth Factor I / analysis*
  • Male
  • Middle Aged
  • Risk Factors


  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I