Harman S M, Metter E J, Blackman M R, Landis P K, Carter H B
The Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
J Clin Endocrinol Metab. 2000 Nov;85(11):4258-65. doi: 10.1210/jcem.85.11.6990.
Insulin-like growth factors (IGFs) may play a role in prostate growth, hyperplasia, and malignancy. High plasma IGF-I has been associated with increased prostate cancer risk. In a prospective, cohort, case-control study in the Baltimore Longitudinal Study on Aging population, we examined prostate volume by magnetic resonance imaging, and prostate-specific antigen (PSA), IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in sera obtained approximately 9 yr before diagnosis of prostate cancer in cases (n = 72) or age-matched controls (n = 127) and in 76 additional Baltimore Longitudinal Study on Aging men (normal subjects) with measured prostate volumes and no prostate cancer. We calculated adjusted odds ratios (OR) by logistic regression, relative risks for significant ORs, and receiver operator curves for prostate cancer, using serum measures alone and in combination. Adjusted ORs for the high vs. low tertile were: for IGF-I, 3.1 [confidence interval (CI), 1.1-8.7]; for IGF-II, 0.2 (CI, 0.07-0.6); for IGFBP-3, 0.71 (CI, 0.3-1.7); and for PSA, 12.5 (CI, 3.8-40.9). For significant ORs, relative risk estimates remained significant at 2.0 for IGF-I, 0.3 for IGF-II, and 5.5 for PSA. Receiver operator curves showed PSA to be the most powerful predictor of prostate cancer. Adding IGF-II to PSA improved prediction. IGF-II was significantly and inversely related (r = -0.219; P < 0.01) and PSA was directly and significantly related (r = 0.461; P < 0.0001) to prostate volume, whereas IGF-I and IBFBP-3 were not. High IGF-I and low IGF-II are independently associated with increased risk of prostate cancer, but PSA level is a much stronger predictor of prostate cancer in the ensuing 10 yr than either IGF-I or IGF-II. The absence of a relationship of IGF-I to prostate size is inconsistent with increased ascertainment in men with large prostates as the source of greater prostate cancer risk associated with IGF-I. Our data suggest that IGF-II may inhibit both prostate growth and development of prostate cancer.
胰岛素样生长因子（IGFs）可能在前列腺生长、增生及恶性肿瘤中发挥作用。高血浆IGF-I与前列腺癌风险增加相关。在巴尔的摩纵向衰老研究人群中的一项前瞻性队列病例对照研究中，我们通过磁共振成像检查了前列腺体积，并检测了病例组（n = 72）或年龄匹配对照组（n = 127）在前列腺癌诊断前约9年采集的血清中的前列腺特异性抗原（PSA）、IGF-I、IGF-II和胰岛素样生长因子结合蛋白-3（IGFBP-3），还检测了另外76名巴尔的摩纵向衰老研究男性（正常受试者）的前列腺体积且这些人无前列腺癌。我们通过逻辑回归计算调整后的优势比（OR）、显著OR的相对风险以及前列腺癌的受试者工作特征曲线，单独使用血清指标及联合使用血清指标进行分析。高与低三分位数的调整后OR分别为：IGF-I，3.1 [置信区间（CI），1.1 - 8.7]；IGF-II，0.2（CI，0.07 - 0.6）；IGFBP-3，0.71（CI，0.3 - 1.7）；PSA，12.5（CI，3.8 - 40.9）。对于显著的OR，IGF-I的相对风险估计为2.0，IGF-II为0.3，PSA为5.5时仍具有显著性。受试者工作特征曲线显示PSA是前列腺癌最有力的预测指标。将IGF-II加入PSA可改善预测效果。IGF-II与前列腺体积呈显著负相关（r = -0.219；P < 0.01），PSA与前列腺体积呈显著正相关（r = 0.461；P < 0.0001），而IGF-I和IGFBP-3与前列腺体积无关。高IGF-I和低IGF-II独立地与前列腺癌风险增加相关，但在随后10年中，PSA水平比IGF-I或IGF-II更能有力地预测前列腺癌。IGF-I与前列腺大小无关，这与将前列腺大者作为与IGF-I相关的更高前列腺癌风险来源的增加的确诊情况不一致。我们的数据表明IGF-II可能抑制前列腺生长及前列腺癌的发生发展。
