Prospective Study of Colorectal Cancer Risk in Men and Plasma Levels of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3

Abstract

Background: Insulin-like growth factor-I (IGF-I) is a potent mitogen for normal and neoplastic cells, whereas IGF-binding protein-3 (IGFBP-3) inhibits cell growth in many experimental systems, Acromegalics, who have abnormally high levels of growth hormone and IGF-I, have higher rates of colorectal cancer, We therefore examined associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospective case-control study nested in the Physicians' Health Study, Methods: Plasma samples were collected at baseline from 14916 men without diagnosed cancer. IGF-I, IGF-II, and IGFBP-3 were assayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up and among 318 age- and smoking-matched control subjects, All P values are two-sided, Results: IGPBP-3 levels correlated with IGF-I levels (r =.64) controlling for IGFBP-3, age, smoking, body mass index (weight in kg/height in m), and alcohol intake, men in the highest quintile for IGF-I had an increased risk of colorectal cancer compared with men in the lowest quintile (relative risk [RR] = 2.51; 95% confidence interval [CI] = 1.15-5.46; P for trend =.02). After controlling for IGF-I and other covariates, men with higher IGFBP-3 had a lower risk (RR = 0.28; 95% CI = 0.12-0.66; P for trend =.005, comparing extreme quintiles), The associations were consistent during the first and the second 7-year follow-up intervals and among younger and older men. IGF-II was not associated with risk. Conclusions : Our findings suggest that circulating IGF-I and IGFBP-3 are related to future risk of colorectal cancer.