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）与以下风险升高相关： 结肠直肠癌、乳腺癌和子宫内膜癌。三种胰岛素抵抗 综合征相关疾病、2型糖尿病、肥胖和久坐的生活方式， 也与这些癌症的风险增加有关，高胰岛素血症是 至少在一定程度上推动了这些关系。胰岛素份额40 与IGF-1的同源性百分比，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了基于胰岛素的癌症风险 水平，没有一个是前瞻性的，样本量足够或足够 控制混杂因素。同样，流行病学数据也很少 关于游离IGF-1和癌症，即使未结合的形式是主要的， 生物活性成分我们小组的一项横断面研究发现， 与乳腺癌的相关性比IGF-1更强。提供明确的 一项关于胰岛素与癌症相关性的前瞻性研究表明， IGF-1是必需的。因此，本申请的目的是 确定高血清胰岛素和游离IGF-1对事件风险的影响 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研究中获得， 倡议（WHI），一个大型的（n= 93，725），种族和地理多样性 年龄在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 研究，检测基线血清空腹血糖、胰岛素、总胰岛素和游离胰岛素 IGF-1、IGF结合蛋白-3（IGFBP-3）和总雌二醇。后续将 平均7年，如果在前18个月内诊断出病例，则排除。我们 具体研究：（1）高血清胰岛素的独立效应 和游离IGF-1对结直肠癌（n=500）、乳腺癌（n=900）和子宫内膜癌的风险 癌症组（n=300）;（2）在亚队列（对照组; n=900）中， 总IGF-1、游离IGF-1和IGFBP-3水平;（3）是否为2型糖尿病 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.