High Levels of Circulating Insulin-Like Growth Factor-I Increase Prostate Cancer Risk: A Prospective Study in a Population-Based Nonscreened Cohort

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Abstract
Purpose: Insulin-like growth factor-I (IGF-I) stimulates proliferation and inhibits apoptosis in prostate cancer cells, and IGF-I has been associated with increased prostate cancer risk in some, but not all, epidemiologic studies. Subjects and Methods: We extended our previous case-control study nested in the Northern Sweden Health and Disease Cohort, a population-based cohort from a region where little prostate specific antigen (PSA) screening is done. Levels of IGF-I and IGF binding protein-3 (IGFBP-3) were measured in prediagnostic blood samples from a total of 281 men who were subsequently diagnosed with prostate cancer after recruitment (median, 5 years after blood collection) and from 560 matched controls. Results: Logistic regression analyses showed increases in prostate cancer risk with increasing plasma peptide levels, up to an odds ratio (OR) for top versus bottom quartile of IGF-I of 1.67 (95% CI, 1.02 to 2.71; P trend = .05), which was attenuated after adjustment for IGFBP-3 to an OR of 1.47 (95% CI, 0.81 to 2.64; P trend = .32). For men younger than 59 years at recruitment, OR for top versus bottom quartile of IGF-I was 4.12 (95% CI, 1.01 to 16.70; P trend = .002), which was significantly stronger than for men older than 59 years (P interaction = .006). For men with advanced cancer, OR for top versus bottom quartile of IGF-I was 2.87 (95% CI, 1.01 to 8.12; P trend = .10). Conclusion: Our data add further support for IGF-I as an etiologic factor in prostate cancer and indicate that circulating IGF-I levels measured at a comparatively young age may be most strongly associated with prostate cancer risk.