PLASMA LEVELS OF IGF-1, IGF-2, AND IGFBP-3 IN WHITE AND AFRICAN-AMERICAN MEN AT INCREASED RISK OF PROSTATE CANCER DONNA L. WINTER, ALEXANDRA L. HANLON, SUSAN L. RAYSOR, DEBORAH WATKINS-BRUNER, WAYNE H. PINOVER, GERALD E. HANKS, AND JAMES V. TRICOLI ABSTRACT Objectives. To further investigate the relationship between the plasma levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone, testosterone, and demographic factors, particularly race, within a group of men at increased risk of prostate cancer development. Methods. Enzyme-linked immunosorbent assays or an immunosorbent assay was used to quantitate the plasma levels of IGF-1, IGF-2, IGFBP-3, growth hormone, and testosterone. The study group consisted of 169 men (85 African-American, 84 white) aged 35 to 69 years, with no personal history of prostate cancer, but having at least one first-degree relative diagnosed with the disease, unless they were African-American. The relationships between the plasma levels and the categorical covariates were assessed using the nonparametric Wilcoxon test and between the continuous variables using Spearman’s correlation coeffi- cient. Results. The mean plasma levels of IGFBP-3 were significantly lower in African-American (2657 ng/mL) than in white (2965 ng/mL) men (P = 0.0062). The plasma levels of IGF-2 were also lower in the African-American (503.5 ng/mL) than in the white (549.1 ng/mL) men (P = 0.0084). Overall, the IGF-1 plasma levels correlated positively with the IGF-2, IGFBP-3, and growth hormone levels and the IGF-2 plasma levels correlated negatively with the testosterone levels. Conclusions. Our results demonstrate that lower plasma levels of IGFBP-3 and IGF-2 are associated with race in a population of men at increased risk of developing prostate cancer. The ability of these markers to predict earlier disease onset is currently under investigation. UROLOGY 58: 614–618, 2001. © 2001, Elsevier Science Inc. T he insulin-like growth factor (IGF) system performs an important role in regulating the processes of proliferation and apoptosis in prostate cancer cells, and IGF-1 is mitogenic for prostatic epithelial cells in vitro. 1–6 Components of the IGF system have been detected in both prostate epithe- lial and stromal cells, where they may participate in autocrine stimulation of epithelial cell growth. 7 In- sulin-like growth factor binding protein-3 (IG- FBP-3) binds to IGF-1, forming a complex that limits IGF-1 bioavailability for binding to the IGF-1 receptor. 8,9 In addition, it has been hypoth- esized that IGFBP-3 may initiate cellular apoptosis through a separate receptor. 10,11 IGFBP-3 has also been detected in prostatic epithelial and stromal cells, 7 and immunohistochemical studies have demonstrated lower levels of the protein in pros- tate cancer than in benign prostate epithelium. 12,13 Although one study failed to detect a correlation between IGF-1 plasma levels and prostate cancer, 14 several previous investigations revealed that the plasma levels of IGF-1 and IGFBP-3 may be predic- tors of prostate cancer risk. 15–17 These studies dem- onstrated a correlation between increased plasma titers of IGF-1 and the development of prostate cancer. One of these studies detected lower IG- FBP-3 plasma levels in men with prostate cancer than in those without. 16 The results of these stud- ies suggest that IGF-1 and IGFBP-3 may be predic- From the Departments of Radiation Oncology and Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania Reprint requests: James V. Tricoli, Ph.D., Cancer Diagnosis Program, National Cancer Institute, 6130 Executive Boulevard, Executive Plaza North, Suite 6035A, Rockville, MD 20852 Submitted: March 20, 2001, accepted (with revisions): May 23, 2001 BASIC SCIENCE © 2001, ELSEVIER SCIENCE INC. 0090-4295/01/$20.00 614 ALL RIGHTS RESERVED PII S0090-4295(01)01273-0