IGF-I LEVELS, IGF-I GENOTYPE, AND PROSTATE CANCER

胰岛素样生长因子-1（IGF-1）是一种多肽，部分介导生长激素对正常发育的影响。然而，IGF-1是一种有丝分裂原，并且在一些实验系统中产生细胞转化并抑制细胞凋亡。因此，有理由怀疑IGF-1在致癌作用中发挥作用，这些怀疑被最近的医生健康研究结果所加强，该研究表明IGF-1的基线水平与随后的前列腺癌发生之间存在强烈的关联。我们建议通过在心血管健康研究（CHS）的男性登记者中进行巢式病例对照研究来进一步深入研究这个问题。CHS是对居住在美国四个社区的65岁以上人群的队列研究，始于1989年。在队列中约225名男性中，他们在1999年底之前患上前列腺癌，并且在人口统计学特征上与病例匹配的其他男性入组者的相同大小的样本中，将从CHS中央血液实验室的冷冻样本中获得病例诊断前获得的血液等分试样。将这些等分试样解冻并测定：1）IGF-1、IGF结合蛋白-3和前列腺特异性抗原（PSA）的水平;和2）IGF-1和IGF-1受体基因型。将比较病例和对照组IGF- 1水平和基因型及其受体基因型的差异，调整IGF结合蛋白-3水平和丰富CHS数据库中确定的其他可能的混杂因素。在分析癌症与血液IGF-1水平的关系时，将特别关注在抽取血液样本时没有前列腺癌证据的男性的结果，即，PSA值正常的人。我们认为，大量的受试者，血液标本的可用性，早于前列腺癌的存在，并纳入相关的遗传特征，以前没有被检查的癌症风险将允许拟议的研究提供一个严格的测试的一个重要假设，前列腺癌的病因。

Insulin-like growth factor-1 (IGF-1) is a polypeptide that, in part, mediates the influence of growth hormone on normal development. However, IGF-1 is a mitogen, and in some experimental systems produces cell transformation and inhibits apoptosis. Thus, there are reasons to suspect IGF-1 of playing a role in carcinogenesis, and these suspicions were heightened by recent results from the Physicians' Health Study, which indicated a strong association between baseline levels of IGF-1 and the subsequent occurrence of prostate cancer. We propose to delve further into this question by conducting a nested case- control study among male enrollees in the Cardiovascular Health Study (CHS). The CHS is a cohort study of persons over 65 years of age residing in four communities in the U.S. which began in 1989. On the approximately 225 men in the cohort who developed prostate cancer through the end of 1999, and on an equal-size sample of other male enrollees matched to the cases on demographic characteristics, an aliquot of blood obtained prior to the time of the case's diagnosis will be obtained from frozen samples in the CHS Central Blood Laboratory. These aliquots will be thawed and assayed for: l) levels of IGF-1, IGF binding protein-3, and prostate-specific antigen (PSA); and 2) IGF-1 and IGF-1 receptor genotypes. Cases and controls will be compared for differences in levels and genotype of IGF- 1 and the genotypes of its receptor, adjusting for levels of IGF binding protein-3 and for other possible confounding factors identified in the rich CHS database. In analyses of cancer in relation to blood IGF-1 levels, particular attention will be given to the results in men with no evidence of prostate cancer at the time the blood specimen had been drawn, i.e., those with a normal PSA value. We believe that the large number of subjects, the availability of blood specimens that predate the presence of prostate cancer, and the incorporation of relevant genetic characteristics that have not previously been examined with respect to cancer risk will allow the proposed study to provide a rigorous test of an important hypothesis regarding the etiology of prostate cancer.