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Insulin-like Growth Factors and Prostate Cancer

A Population-based Case-Control Study in China

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20852 [A. P. C., C-M. F., T. R. F., M. P. M., R. G. Z., J. F. F., A. W. H.]; Cancer Prevention Research Unit, Lady Davis Research Institute, McGill University, Montreal, Canada H3T 1E2 [M. P.]; Shanghai Cancer Institute, Shanghai, 200032 China [Y-T. G., J. D.]; Department of Obstetrics and Gynecology, School of Medicine, University of Southern California, Los Angeles, California 90033 [F. Z. S.]; and Armed Forces Institute of Pathology, Washington, D. C. 20306 [I. A. S., F. K. M.]

Insulin-like growth factors (IGFs) have potent mitogenic and antiapoptotic effects on prostate epithelial cells. Through modulation of IGF bioactivity and other mechanisms, IGF-binding proteins (IGFBPs) also have growth-regulatory effects on prostate cells. Recently, IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western populations. To assess whether IGF-I, IGF-II, IGFBP-1, or IGFBP-3 are also associated with prostate cancer in a low-risk population, we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 randomly selected population controls in Shanghai, China. Relative to the lowest quartile of IGF-I levels, men in the highest quartile had a 2.6-fold higher prostate cancer risk, with a significant trend [odds ratio (OR) = 2.63; 95% confidence interval (95% CI) = 1.19–5.79; P_trend = 0.01]. In contrast, men in the highest quartile of IGFBP-3 levels had a 46% decreased risk relative to the lowest quartile (OR = 0.54; 95% CI = 0.26–1.15; P_trend = 0.08). A similar but less distinct result was observed for IGFBP-1 (OR = 0.60; 95% CI = 0.31–1.17; P_trend = 0.25). Men in the highest quartile for the IGF-I:IGFBP-3 molar ratio (an indirect measure of free IGF-I) had a 2.5-fold higher risk compared with the lowest quartile (OR = 2.51; 95% CI = 1.32–4.75, P_trend < 0.001). These associations were more pronounced after adjustment for serum 5-androstane-3,17ß-diol glucuronide and sex hormone-binding globulin levels. There was no significant association with IGF-II levels. Our findings in a low-risk population provide evidence that IGF-I, IGFBP-3, and IGFBP-1 are determinants of prostate cancer and indicate that additional studies are needed to evaluate their effects on ethnic and geographic incidence differentials and to elucidate carcinogenic mechanisms.

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