Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):484-91. doi: 10.1158/1055-9965.EPI-09-0836.
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.
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.
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.
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.
酸不稳定亚基（ALS）在胰岛素样生长（IGF）系统中发挥作用，通过与结合蛋白（IGFBP）-3结合形成三元复合物来结合循环中的 IGF-I，从而防止 IGF-I 穿过内皮屏障。鉴于 IGF 系统在前列腺癌中的作用，ALS 可能通过调节 IGF-I 水平或生物利用度来影响致癌作用。
我们进行了一项前瞻性研究，该研究嵌套在医师健康研究中，以检查 ALS、游离 IGF-I 和前列腺癌。我们检测了 545 例新发病例和 545 例匹配对照者的循环 ALS 和 IGF 成分水平。我们计算了调整生活方式因素、总 IGF-I 和 IGFBP3 后相对风险（RR）和 95%置信区间（95%CI）。
ALS 与总 IGF-I（r = 0.58）、IGFBP3（r = 0.68）和游离 IGF-I（r = 0.36）呈正相关。比较最高和最低四分位数，我们发现游离 IGF-I 与前列腺癌风险之间没有关联（RR，0.9；95%CI，0.6-1.3）。相比之下，ALS 与第二（RR，1.5；94%CI，1.0-2.3）、第三（RR，1.6；94%CI，1.1-2.5）和第四四分位组（RR，1.4；94%CI，0.9-2.1）的男性风险呈正相关与最低四分位数相比。该相关性在晚期肿瘤中更强（RR，2.0；94%CI，0.8-4.6）。有迹象表明 ALS 和总 IGF-I 之间存在交互作用，即高循环 IGF-I 与 ALS 水平较低但不高的男性中晚期前列腺癌风险增加相关。
血浆 ALS 与前列腺癌风险呈正相关，并且可能与 IGF-I 在生物学上相互作用，从而影响致癌作用。这些数据为 IGF 轴在前列腺癌中的作用提供了进一步的支持。
