Insulin-Like Growth Factor-I, Insulin-Like Growth Factor Binding Protein-3 and Risk of Benign Prostate Hyperplasia in the Prostate Cancer Prevention Trial

Background—We investigated whether peptides involved in cellular proliferation and apoptosis, [insulin-like growth factor I (IGFI) and its major binding protein (insulin-like growth factor binding protein 3)], predicted risk of benign prostate hyperplasia (BPH). Methods—We conducted a nested-case control study in the placebo arm of the Prostate Cancer Prevention Trial (PCPT). Cases (n = 727) were men with surgical or medical treatment for BPH; two or more IPSS scores> 14; or two scores of at least five points over baseline one of which was ≥ 12. Controls (n=727) were frequency matched by age to cases, reported no BPH treatment, and no IPSS score> 8. Cases and controls remained on the PCPT placebo and were followed closely until their 7-year PCPT anniversary. Baseline serum was analyzed for IGFI and IGFBP3. Unconditional logistic regression and polytomous regression estimated the multivariate-adjusted odds ratio for BPH risk. Results—IGFBP3 was inversely and the IGFI:IGFBP3 ratio was positively associated with BPH risk, but findings were statistically significant only for men with severe symptoms (OR=0.60, 95% CI = 0.40–0.90 for the fifth vs. first quintile of IGFBP3, p, trend = 0.01). Associations did not differ by age (< 65 or ≥ 65 years), and there was a suggestion that the IGFI:IGFBP3 – BPH risk association may be stronger among overweight men. Conclusions—A high IGFI:IGFBP3 ratio was associated with increased BPH risk, and high serum IGFBP3 was associated with decreased BPH risk among men with severe symptoms. These results confirm findings from other recent studies. Keywords prostatic hyperplasia; insulin-like growth factors; insulin-like growth factor binding proteins; case