Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of prostate cancer in the PSA era

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Abstract
Objective The insulin-like growth factor (IGF) axis is thought to contribute to the growth and progression of prostate cancer. Some prospective studies support a direct association between IGF-1 and prostate cancer, in particular advanced disease, whereas both inverse and direct associations with prostate cancer have been reported for insulin-like growth factor binding protein-3 (IGFBP-3), the major IGF-1 binding protein in circulation. We prospectively investigated the associations of plasma IGF-1 and IGFBP-3 concentrations with prostate cancer detected in the PSA era. Methods: We identified 462 prostate cancer cases diagnosed after providing a blood specimen in 1993, but before January 1998 among men in the Health Professionals Follow-up Study. Controls were 462 age-matched men without prostate cancer who had had a PSA test after providing a blood specimen. We measured plasma concentrations of IGF-1 and IGFBP-3 by ELISA. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer. Results: Men with higher concentrations of IGF-1 (comparing extreme quartiles OR=1.37, 95% CI 0.92–2.03, p-trend=0.05) and IGFBP-3 (OR=1.62, 95% CI 1.07–2.46, p-trend=0.08) had a higher risk of prostate cancer. After mutual statistical adjustment, these associations were attenuated for both IGF-1 (OR=1.17, 95% CI 0.69–1.99, p-trend=0.29) and IGFBP-3 (OR=1.40, 95% CI 0.80–2.44, p-trend=0.56). We found no significant association of IGF-1 with regionally invasive or metastatic (≥T3b, N1, or M1) prostate cancer, although the number of these cases was small (n=42). Conclusions: Our findings for IGF-1 and prostate cancer diagnosed in the PSA era are similar to most previous studies, albeit weaker in magnitude. Our suggestive positive findings for IGFBP-3 are similar to some studies, but in direct contrast to others.

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