Insulin-like growth factor (IGF) related components and incidence of cancer in a nested case-control study

IGF1 is a potent mitogen, but IGF-binding protein-3 (BP3) binds and inhibits IGF1. To elucidate the relationship those and the risk of tumorigenesis, we analyzed associations of serum levels of IGF1 and BP3 with incidence of cancer in a prospective case-control study nested in the JACC Study. A baseline survey was conducted from 1988 and 39,242 subjects (35%) donated blood samples. Those who had been diagnosed as solid tumors by 1997 were regarded as cases. For each case, we randomly selected 2 or 3 controls, matching for gender, age and residential area. 1519 cases and 3904 controls are eligible for this study.After controlling for smoking, BMI, and alcohol intake, participants with high total and free BP3, represented by molar difference of (BP3 - IGF1), had the risk of future cancer (p for trend = 0.013 and 0.021, respectively), but those with IGF1 not. Limiting subjects to those followed for 3 years weakened the negative associations of total- and free-BP3, whereas the positive relation of free-IGF1, estimated by molar ratio of IGF1/BP3, was revealed (p for trend = 0.047).Our findings might suggest that serum IGF1 and BP3 are related to future risk of solid tumors in Japanese.