Insulin-like growth factors and prostate cancer: A population-based case-control study in China

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-regul atory effects on prostate cells. Recently, IGF-I and IGFBP-3 have been impl icated in prostate cancer risk among Western populations. To assess whether IGF-I, IGF-II, IGFBP-1, or IGFBP3 are also associated with prostate cancer in a tow-risk population, we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 randomly selected popula tion 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 r isk, with a significant trend [odds ratio (OR) = 2.63; 95% confidence inter val (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 les s 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 ra tio (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 alpha -androstane-3 alpha ,17 beta -diol glucuronide and sex hormone-binding glo bulin 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 s tudies are needed to evaluate their effects on ethnic and geographic incide nce differentials and to elucidate carcinogenic mechanisms.