Colorectal Cancer And The Growth Hormone/Insulin-Like Growth Factor-I Axis (pp. 65-96)
Authors: Bustin, Stephen A.; Jenkins, Paul J. (Centre for Academic Surgery, Department of Endocrinology; London )
Abstract: Colorectal cancer risk is determined by a combination of environmental factors and genetic predisposition. Recent evidence suggests that dietary and related factors such as physical activity and body size may influence colorectal cancer risk through their effects on the serum concentration of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein (IGFBP)-3, two members of the growth hormone (GH)/IGF-I axis. The GH/IGF-I axis is involved in both human development as well as the maintenance of normal function and homeostasis in most cells of the body. In addition to their classical role as endocrine hormones, its members regulate a wide range of biological functions such as cell proliferation, differentiation and apoptosis through paracrine and autocrine mechanisms. This is particularly evident in its critical role as a regulator of rapidly renewing epithelial cell populations such as those found in the colon. Here its appropriate expression is responsible for the ordered migration of differentiating cells from the bottom towards the top of the colonic crypt and their eventual demise through apoptosis. During cancer development this complex network regulating tissue homeostasis breaks down, with inappropriate expression of the GH/IGF-I axis making an important contribution. The increased understanding of the molecular mechanisms and signalling pathways regulated by the GH/IGF-I axis has started to provide significant insights into the aetiology, prevention and therapy for this cancer.