Free insulin-like growth factor-I and breast cancer risk

Insulin-like growth factor-I (IGF-I) has mitogenic and anti-apoptotic effec ts on breast cancer cells, Epidemiologic studies have shown that high plasm a levels of IGF-I and low levels of IGF binding protein (BP)-3 are associat ed with increased risk of breast cancer in premenopausal women, The actions of ICF-I are mediated through the ICF-I receptor (IGF-IR) and are regulate d by IGFBPs, In circulation, most of the IGF-I binds to IGFBP-3, and bindin g of IGF-I to ICFBP-3 inhibits the actions of IGF-I. Since free IGF-I, whic h does not bind to IGFBPs, can readily cross the endothelial barrier to int eract with IGF-IR, circulating free IGF-I is thought to be more relevant to the biologic activity of IGF-I, To examine the association of free IGF-I w ith breast cancer, we compared free ICF-I levels between 40 newly diagnosed breast cancer patients and 40 age- and race-matched healthy controls. Plas ma levels of free IGF-I, total IGF-I and IGF-II, as well as total, intact a nd fragment IGFBP-3, were measured using commercial immunoassay kits, The a ssociation between IGF-I and breast cancer was examined using the condition al logistic regression analysis. Analysis of correlation (Spearman) showed that free IGF-I was correlated with total IGF-I and IGFBP-3 but not with IG F-II, The odds ratios for breast cancer patients having high plasma IGF-I ( greater than or equal to median) after adjusting for menopausal status and IGFBP-3 were 2.00 (p < = 0.376) for total IGF-I and 6.31 (p < = 0.047) for free ICF-I, A high ratio of ICF-I to IGFBP-3 was also associated with breas t cancer (p < 0.05). No association was found for ICF-II, nor for total, in tact and fragment IGFBP-3, The findings of this study suggest that measurin g free ICF-I in circulation is more useful than measuring total IGF-I with respect to evaluation of an association between ICF-I and breast cancer ris k. (C) 2001 Wiley-Liss, Inc.