Insulin and IGF In female colon, breast, uterine cancer

描述(由申请人提供)：越来越多的证据表明 血清胰岛素样生长因子-1(IGF-1)与高血压风险增加相关 结直肠癌、乳腺癌和子宫内膜癌。三种胰岛素抵抗 与症状相关的疾病、2型糖尿病、肥胖和久坐不动的生活方式， 也与这些癌症的更大风险有关，高胰岛素血症 假设是为了推动这些关系，至少在一定程度上。胰岛素股40 与IGF-1有百分之百的同源性，生物学研究表明两者都是有丝分裂原。 然而，很少有流行病学研究评估基于胰岛素的癌症风险。 水平，没有一个具有足够的样本量或足够的预期 对混杂因素的控制。同样，流行病学数据也很稀少。 关于游离IGF-1与癌症，尽管非结合形式是主要的 生物活性成分。我们小组的一项横断面研究发现，免费的IGF-I更多 与总IGF-1相比，IGF-1与乳腺癌的相关性更强。以提供明确的 它们与癌症关联的证据，胰岛素和胰岛素的前瞻性研究 免费的IGF-1是必要的。因此，此应用程序的目的是 确定高血清胰岛素和游离IGF-1对事件风险的影响 绝经后妇女的结直肠癌、乳腺癌和子宫内膜癌。标本 数据将从妇女健康观察性研究中获得 倡议(WHI)，一个种族和地理多样化的大型(n=93,725) 50-79岁的绝经后妇女队列。我们建议进行一个病例队列 研究，测试基线血清的空腹血糖、胰岛素、总和游离 胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3(IGFBP-3)和总雌二醇。后续行动将 平均7年，不包括前18个月确诊的病例。我们的 具体目的是研究：(1)高血清胰岛素的独立作用 和游离IGF-1对结直肠癌(n=500)、乳房(n=900)和子宫内膜风险的影响 癌症(n=300)；(2)在亚队列(对照；n=900)中，相关因素 对总IGF-1、游离IGF-1和IGFBP-3水平的影响；(3)2型糖尿病是否 是结直肠癌、乳腺癌和子宫内膜癌的独立危险因素， 控制胰岛素抵抗、IGF-1和IGFBP-3。

DESCRIPTION (provided by applicant): Increasing evidence indicates that high serum insulin-like growth factor-1 (IGF-1) is associated with elevated risk of colorectal, breast, and endometrial cancer. Three Insulin Resistance Syndrome-related conditions, type 2 diabetes, obesity, and sedentary lifestyle, are also associated with greater risk of these cancers, and hyperinsulinemia is hypothesized to drive these relationships, at least in part. Insulin shares 40 percent homology with IGF-1, and biologic studies suggest both are mitogens. However, few epidemiologic studies have evaluated cancer risk based on insulin levels, and none have been prospective with sufficient sample size or adequate control for confounders. Similarly, there are sparse epidemiologic data regarding free IGF-1 and cancer, even though the unbound form is the main bioactive component. A cross-sectional study by our group found free IGF-I more strongly associated with breast cancer than total IGF-1. To provide definitive evidence of their associations with cancer, a prospective study of insulin and free IGF-1 is necessary. Therefore, the purpose of this application is to determine the effects of high serum insulin and free IGF-1 on risk of incident colorectal, breast and endometrial cancer in postmenopausal women. Specimens and data will be obtained from the Observational Study of the Women's Health Initiative (WHI), a large (n=93,725), ethnically and geographically diverse cohort of postmenopausal women aged 50-79. We propose conducting a case-cohort study, testing baseline serum for fasting glucose, insulin, total and free IGF-1, IGF binding protein-3 (IGFBP-3), and total estradiol. Follow-up will average 7 years, with cases excluded if diagnosed in the first 18 months. Our specific aims are to study: (1) The independent effects of high serum insulin and free IGF-1 on risk of colorectal (n=500), breast (n=900) and endometrial cancers (n=300); (2) Among the subcohort (controls; n=900), the factors related to levels of total IGF-1, free IGF-1, and IGFBP-3; (3) Whether type 2 diabetes is an independent risk factor for colorectal, breast and endometrial cancers, controlling for insulin resistance, IGF-1 and IGFBP-3.