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Epidemiology and Prevention |
Cancer Prevention Studies Branch, Center for Cancer Research [K. W., J. A. T., P. R. T.] and Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics [D. A.], National Cancer Institute, Bethesda, Maryland 20892; Cancer Prevention Research Unit, Departments of Medicine and Oncology, Lady Davis Research Institute of the Jewish General Hospital and McGill University, Montreal, Quebec, Canada [M. P.]; Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland [T. C.]; and Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland [J. V.]
Recent epidemiological studies suggest an association between higher blood levels of insulin-like growth factor I (IGF-I) and increased risk of prostate cancer. We evaluated the association between prediagnostic levels of IGF-I and insulin-like growth factor binding protein 3 (IGFBP-3) and prostate cancer risk in a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Within the same cohort (using different cases and controls who had sequential serum samples available) we also examined changes in serum IGF-I and IGFBP-3 levels over time by case status. The risk association study included incident prostate cancer cases (n = 100) diagnosed at least 5 years after baseline blood draw (range, 5–12 years; median 9 years) and frequency-matched (4:1) controls. The sequential serum study included all of the prostate cancer cases (n = 21) with prediagnostic (2–3 years before diagnosis) and diagnostic serum available, and pair-matched controls (1:1). An ELISA was used to quantitate serum levels of IGF-I and IGFBP-3 for both studies. The association between IGF-I or IGFBP-3 and prostate cancer risk was assessed using conditional logistic regression, and paired t tests were used to evaluate case-control differences in change in serum analytes over time. We found no significant association between either IGF-I or IGFBP-3 and prostate cancer risk. In a multivariate analysis, we observed an odds ratio of 0.52 (95% confidence interval, 0.23–1.16) for the fourth versus the first quartile of serum IGF-I. Serum IGF-I, but not IGFBP-3, increased significantly over time in cases (18% increase) but not controls (4% decrease; P = 0.02). In contrast to previous reports, we found no evidence to support a causal association between serum IGF-I or IGFBP-3 and the risk of prostate cancer. It is possible that serum IGF-I may be serving as a tumor marker rather than an etiologic factor in prostate cancer.
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