, Volume 16, Issue 3, pp 255-262

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.

Supported by Public Health Service grants CA55075 and CA72036 (National Cancer Institute) and HL35464 (National Heart, Lung, and Blood Institute) from the National Institutes of Health. Dr. Platz is supported by the Bernstein Young Investigator’s Award.