Plasma levels of acid-labile subunit, free insulin-like growth factor-1, and prostate cancer risk: a prospective study

Abstract

Background: The acid-labile subunit (ALS) acts in the insulin-like growth (IGF) system by binding circulating IGF-I in a ternary complex with binding protein (IGFBP)-3 to prevent IGF-I from crossing the endothelial barrier. Given the role of the IGF system in prostate cancer, ALS may influence carcinogenesis by modulating IGF-I levels or bioavailability.Methods: We undertook a prospective study nested in the Physicians' Health Study to examine ALS, free IGF-I, and prostate cancer. We assayed circulating levels of ALS and IGF components among 545 incident cases and 545 matched controls. We calculated relative risks (RR) and 95% confidence intervals (95% CI) adjusted for life-style factors, total IGF-I, and IGFBP3.Results: ALS was positively correlated with total IGF- I (r = 0.58), IGFBP3 (r = 0.68), and free IGF- I (r = 0.36). Comparing highest versus lowest quartiles, we found no association between free IGF- I and prostate cancer risk (RR, 0.9; 95% CI, 0.6-1.3). In contrast, ALS was positively associated with risk among men in the 2nd (RR, 1.5; 94% CI, 1.0-2.3), 3rd (RR, 1.6; 94% CI, 1.1-2.5), and 4th quartiles (RR, 1.4; 94% CI, 0.9-2.1) compared with lowest quartile. The association was stronger for advanced stage tumors (RR, 2.0; 94% CI, 0.8-4.6). There was a suggestion of an interaction between ALS and total IGF-I, whereby high circulating IGF- I was associated with an increased risk of advanced prostate cancer among men with low but not higher ALS levels.Discussion: Plasma ALS is positively associated with prostate cancer risk, and may interact biologically with IGF- I to affect carcinogenesis. These data provide further support for the role of the IGF axis in prostate cancer. Cancer Epidemiol Biomarkers Prev; 19(2); 484-91.