Plasma insulin-like growth factor-I, insulin-like growth factor-binding proteins, and prostate cancer risk: a prospective study

Background: Recent studies have suggested that men with elevated plasma lev els of insulin-like growth factor-I (IGF-I) may have an increased risk of p rostate cancer. Furthermore, IGF-binding proteins (IGFBPs) and insulin can modulate the activity of IGF-I, In this study, we sought to determine the r ole of IGF-I as well as IGFBPs-1, -2, and -3 and insulin as possible etiolo gic factors for prostate cancer. Methods: We conducted a nested case-contro l study within the Northern Sweden Health and Disease Cohort Study. We meas ured levels of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, and insulin in plasma samp les from 149 men who had a diagnosis of prostate cancer between I month and 10 Sears after blood collection and among 298 control men. All statistical tests are two-sided. Results: Case subjects had statistically significantl y higher mean levels of IGF-I than control subjects (229 ng/mL; 95% confide nce interval [CT] = 218-240 ng/mL] versus 214 ng/mL [95% CI = 208-221 ng/mL ]; P = .02) and IGFBP-3 (2611 ng/mL [95% CI = 2518-2704 ng/mL] versus 2498 ng/mL [95% CI = 2437-2560 ng/mL]; P = .04). Conditional logistic regression analyses showed increases in prostate cancer risk with rising levels of IG F-I (P-for trend = .02) and IGFBP-3 (P-for trend = .03). In case subjects y ounger than 59 years at the time of blood collection, the risk associated w ith increased IGF-I was higher (P-for trend = .01), whereas the risk associ ated with increased IGFBP-3 was lower (P-for trend = .44) than the correspo nding risks in the full cohort. Prostate cancer risk was not associated wit h levels of IGFBP-1, IGFBP-2, or insulin. Conclusions: Prostate cancer risk is increased in men with elevated plasma IGF-I, This association was parti cularly strong in younger men in this study, suggesting that circulating IG F-I mag be specifically involved in the early pathogenesis of prostate canc er.