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

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Abstract

Background

Insulin-like growth factor-I (IGF-I) is a potent mitogen for normal andneoplastic cells, whereas IGF-binding protein-3 (IGFBP-3) inhibits cell growth in manyexperimental systems. Acromegalics, who have abnormally high levels of growth hormone andIGF-I, have higher rates of colorectal cancer. We therefore examined associations of plasmalevels of IGF-I and IGFBP-3 with the risk of colorectal cancer in a prospective case-control studynested in the Physicians' Health Study.

Methods

Plasma samples were collected atbaseline from 14 916 men without diagnosed cancer. IGF-I, IGF-II, and IGFBP-3 wereassayed among 193 men later diagnosed with colorectal cancer during 14 years of follow-up andamong 318 age- and smoking-matched control subjects. All P values are two-sided.

Results

IGFBP-3 levels correlated with IGF-I levels (r=.64) and with IGF-II levels (r=.90). After controlling for IGFBP-3, age, smoking, body massindex (weight in kg/[height in m]2), 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 extremequintiles). The associations were consistent during the first and the second 7-year follow-upintervals 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 futurerisk of colorectal cancer.

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