Serum levels of insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-3, and prostate-specific antigen as predictors of clinical prostatecancer

Insulin-like growth factors (IGFs) may play a role in prostate growth, hype rplasia, and malignancy. High plasma IGF-I has been associated with increas ed prostate cancer risk. In a prospective, cohort, case-control study in th e Baltimore Longitudinal Study on Aging population, we examined prostate vo lume by magnetic resonance imaging, and prostate-specific antigen (PSA), IG F-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in sera obtained approxima tely 9 yr before diagnosis of prostate cancer in cases (n = 72) or age-matc hed controls (n = 127) and in 76 additional Baltimore Longitudinal Study on Aging men (normal subjects) with measured prostate volumes and no prostate cancer. We calculated adjusted odds ratios (OR) by logistic regression, re lative risks for significant ORs, and receiver operator curves for prostate cancer, using serum measures alone and in combination. Adjusted ORs for th e high vs, low tertile were: for IGF-I, 3.1 [confidence interval (CI), 1.1- 8.7]; for IGF-II, 0.2 (CI, 0.07-0.6); for IGFBP-3, 0.71 (CI, 0.3-1.7); and for PSA, 12.5 (CI, 3.8-40.9). For significant ORs, relative risk estimates remained significant at 2.0 for IGF-I, 0.3 for IGF-II, and 5.5 for PSA. Rec eiver operator curves showed PSA to be the most powerful predictor of prost ate cancer. Adding IGF-II to PSA improved prediction. IGF-II was significan tly and inversely related (r = -0.219; P < 0.01) and PSA was directly and s ignificantly related (r = 0.461; P < 0.0001) to prostate volume, whereas IG F-I and IBFBP-3 were not. High IGF-I and low IGF-II are independently assoc iated with increased risk of prostate cancer, but PSA level is a much stron ger predictor of prostate cancer in the ensuing 10 yr than either IGF-I or IGF-II. The absence of a relationship of IGF-I to prostate size is inconsis tent with increased ascertainment in men with large prostates as the source of greater prostate cancer risk associated with IGF-I. Our data suggest th at IGF-II may inhibit both prostate growth and development of prostate canc er.