Wolpin Brian M, Michaud Dominique S, Giovannucci Edward L, Schernhammer Eva S, Stampfer Meir J, Manson JoAnn E, Cochrane Barbara B, Rohan Thomas E, Ma Jing, Pollak Michael N, Fuchs Charles S
Department of Medical Oncology, Dana-Farber Cancer Institute, MA 02115, USA.
Cancer Res. 2007 Aug 15;67(16):7923-8. doi: 10.1158/0008-5472.CAN-07-0373.
Insulin-like growth factor (IGF)-I has growth-promoting effects on pancreatic cancer cells, and elevated fasting serum insulin has been linked to pancreatic cancer risk. IGF binding protein-1 (IGFBP-1) is a downstream target of insulin and inhibits IGF-I activity. To investigate whether prediagnostic plasma levels of IGFBP-1 are associated with pancreatic cancer risk, we did a prospective, case-control study nested within the Health Professionals Follow-up Study, the Nurses' Health Study, the Physicians' Health Study, and the Women's Health Initiative. We assayed circulating IGFBP-1 among 144 pancreatic cancer cases that occurred >or=4 years after plasma collection and in 429 controls, matched for date of birth, prospective cohort, smoking status, and fasting status. When compared with participants in the three highest quartiles of plasma IGFBP-1, those in the lowest quartile experienced a relative risk (RR) for pancreatic cancer of 2.07 [95% confidence intervals (95% CI), 1.26-3.39], after adjusting for other risk factors, including circulating IGF-I, IGF binding protein-3, and C-peptide. Only participants in the lowest quartile of plasma IGFBP-1 showed an elevated risk of pancreatic cancer. The influence of low plasma IGFBP-1 became progressively stronger with time; among cases diagnosed >or=8 years after blood collection, the adjusted RR was 3.47 (95% CI, 1.48-8.14), comparing the bottom versus the top three quartiles. The influence of plasma IGFBP-1 was most marked among participants who never smoked cigarettes (RR, 3.30; 95% CI, 1.48-7.35). Among participants in four U.S. prospective cohort studies, low plasma IGFBP-1 levels significantly predicted an increased risk of pancreatic cancer.
胰岛素样生长因子（IGF）-I对胰腺癌细胞具有促生长作用，空腹血清胰岛素升高与胰腺癌风险相关。IGF结合蛋白-1（IGFBP-1）是胰岛素的下游靶点，可抑制IGF-I的活性。为了研究诊断前血浆IGFBP-1水平是否与胰腺癌风险相关，我们在健康专业人员随访研究、护士健康研究、医生健康研究和妇女健康倡议中开展了一项前瞻性病例对照研究。我们检测了血浆采集后≥4年发生的144例胰腺癌病例以及429例对照者的循环IGFBP-1水平，这些对照者在出生日期、前瞻性队列、吸烟状况和空腹状态方面进行了匹配。与血浆IGFBP-1处于最高三分位数的参与者相比，处于最低三分位数的参与者在调整了包括循环IGF-I、IGF结合蛋白-3和C肽在内的其他风险因素后，患胰腺癌的相对风险（RR）为2.07 [95%置信区间（95%CI），1.26 - 3.39]。只有血浆IGFBP-1处于最低三分位数的参与者显示出胰腺癌风险升高。血浆IGFBP-1水平低的影响随时间推移逐渐增强；在采血后≥8年诊断的病例中，比较最低三分位数与最高三分位数，调整后的RR为3.47（95%CI，1.48 - 8.14）。血浆IGFBP-1的影响在从不吸烟的参与者中最为明显（RR，3.30；95%CI，1.48 - 7.35）。在美国四项前瞻性队列研究的参与者中，血浆IGFBP-1水平低显著预示着患胰腺癌风险增加。
