Prospective study of prostate cancer in relation to serum concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Free

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In experimental systems, insulin-like growth factors play a role in prostate development and growth through regulation of cell proliferation, differentiation and apoptosis, and their over-expression leads to transformation and cancer progression. There have been several prospective epidemiologic studies investigating the association between serum levels of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 ratio and the risk of prostate cancer, but the results have been conflicting. To further examine this question, we conducted a nested case-control study within the Cardiovascular Health Study (CHS) cohort. Using immunoradiometric assay kits from Diagnostic Systems Laboratories, Inc. (DSL-5600 Active IGF-1 with Extraction, DSL-6600 Active IGFBP-3, Webster, Texas), we measured concentrations of IGF-1 and IGFBP-3 in men diagnosed with prostate cancer between 1990 and 1999 (n = 174) on serum samples obtained one to nine years (mean = 3.36 years, sd = 1.63 years) prior to diagnosis. Similar measurements were made on serum samples of 174 male CHS participants who did not develop prostate cancer, matched to the cases on year in which the sample was drawn, survival until the date of diagnosis in the corresponding case, race, and age. IGF-1 levels were not positively associated with prostate cancer risk. Relative to men whose IGF-1 levels were in the lowest fourth of the distribution, the risks in men in the 2^nd, 3^rd and upper fourth were 0.77 (95% CI 0.43–1.38), 0.73 (95% CI0.41–1.30), and 0.67 (95% CI 0.37–1.25), respectively. An analysis restricted to cases with regional or distant involvement gave similar results. An increase in the IGFBP-3 levels, on the other hand, was associated with decreased risk: the corresponding relative risks were 0.91 (95% CI 0.49–1.68), 0.47 (95% CI 0.25–0.94), and 0.65 (95% CI 0.35–1.20). For molar IGF-1/IGFBP-3 ratio, the relative risks were 0.71 (95% CI 0.40–1.27), 0.83 (95% CI 0.48–1.44), and 0.76 (95% CI 0.43–1.36), respectively. These results do not support the hypothesis that men with relatively high serum levels of IGF–1 are at increased risk of prostate cancer.