The acid-labile subunit (ALS) acts in the insulin-like growth (IGF) system by binding circulating IGF1 in a ternary complex with binding protein (IGFBP)-3 to prevent IGF1 from crossing the endothelial barrier. Given the role of the IGF system in prostate cancer, ALS may influence carcinogenesis by modulating IGF1 levels or bioavailability.
Materials and Methods
We undertook a prospective study nested in the Physicians’ Health Study to examine ALS, free IGF1 and prostate cancer. We assayed circulating levels of ALS and IGF components among 545 incident cases and 545 matched controls. We calculated relative risks and 95% confidence intervals (RR, 95% CI) adjusted for lifestyle factors, total IGF1 and IGFBP3.
ALS was positively correlated with total IGF1 (r=0.58), IGFBP3 (r=0.68), and free IGF1 (r=0.36). Comparing highest versus lowest quartiles, we found no association between free IGF1 and prostate cancer risk (0.9, 0.6–1.3). In contrast, ALS was positively associated with risk among men in the 2nd (1.5, 1.0–2.3), 3rd (1.6, 1.1–2.5) and 4th quartiles (1.4, 0.9–2.1) compared to lowest quartile. The association was stronger for advanced stage tumors (2.0, 0.8–4.6). Among men with low ALS, high total IGF1 was associated with a substantial increase in advanced prostate cancer (9.3, 1.7–51.3), while high IGF1 did not confer risk for those with higher ALS levels.
Plasma ALS is positively associated with prostate cancer risk, and may interact biologically with IGF1 to affect carcinogenesis. These data provide further support for the role of the IGF axis in prostate cancer.