Insulin-Like Growth Factor-I: a Key Regulator of Human Cancer Risk?

Extract

In this issue of the Journal, Ma et al. ( 1 ) report the results of a nested case-control study that show an association between colorectal cancer risk in men and elevated plasma levels of insulin-like growth factor-I (IGF-I) and decreased plasma levels of IGF-binding protein-3 (IGFBP-3). Importantly, this study demonstrates these effects by using plasma samples drawn years before the clinical appearance of the tumor, thus minimizing the chance that plasma levels are influenced by the disease process. This study follows reports demonstrating associations between levels of IGF-I and/or IGFBP-3 and the risk for cancers of the breast, prostate, and lung, suggesting that IGF-I is an important indicator of risk for the most prevalent forms of cancer in Western society ( 2 - 5 ). In fact, IGF-I levels appear to have a stronger association than most other risk factors for these common cancers.

IGF-I is unique as a peptide growth factor. In addition to autocrine/paracrine functions demonstrated in numerous tissues, it serves as an endocrine hormone promoting postnatal somatic growth and maintaining lean tissue mass ( 6 ). IGF-I effects are modulated by a family of high-affinity BPs. IGF-I and its principal carrier protein, IGFBP-3, are produced primarily by the liver. Hepatic IGF-I synthesis is regulated by growth hormone (GH) and caloric intake and serves to integrate anabolic signals from the pituitary with signals related to nutritional status. In contrast to insulin, which is involved in short-term regulation of energy metabolism, changes in IGF-I levels occur over a longer term of days to weeks. Dietary restriction, which decreases the serum concentration of IGF-I in both humans and rodents, reduces the incidence of cancer in many rodent models ( 7 , 8 ). Caloric excess, on the other hand, may increase plasma IGF-I in humans ( 9 ). Perhaps part of the link between diet and cancer risk might be due to IGF-I and IGFBP-3.