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

Abstract 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.