URINARY ESTROGEN METABOLITES AND BREAST CANCER RISK

在1989- 1990年，我们收集了32,826名参加护士健康研究队列的妇女的血液样本并将其存档。我们最近得到资助，从1989-90年间提供第一次血液样本的18169名妇女中收集第二次血液样本。作为该项目的一部分，我们将评估一些血浆雌激素（如雌二醇、雌酮、硫酸雌酮）和其他激素与绝经后妇女乳腺癌风险的关系。然而，越来越多的证据支持特定雌激素代谢物（如2-OH和4-OH雌酮和雌二醇）在乳腺癌病因学中的作用。这些代谢物最常在尿液中测量，而在血液中测量它们需要大量的量（超过我们目前收集的样本所能合理提供的量）。因此，当前提案的具体目标是收集并存档18,169名妇女的20毫升尿液样本，我们目前正在为她们收集血液样本。这将使我们能够前瞻性地评估尿雌激素代谢物与乳腺癌风险之间的关系，并最终评估其他假设（例如，雌激素代谢物与子宫内膜癌风险，植物雌激素水平与癌症风险）。在这个申请中，我们只需要资金来收集和储存尿液样本——我们不需要资金来对样本进行实验室分析。由于已经为18169名妇女的血液样本收集提供了资金，因此收集和储存尿液样本的额外成本很小。此外，该申请符合R03的要求，因为资金将用于计划复杂的流行病学调查。我们相信这是一个独特的机会，以非常合理的成本收集和存档尿液样本，这将允许未来对激素和乳腺癌风险相关的几个非常重要的问题进行前瞻性评估。

In 1989-90, we collected and archived blood samples from each of 32,826 women participating in the ongoing Nurses' Health Study cohort. We were recently funded to collect a second blood sample from 18,169 of the women who provided a first blood sample in 1989-90. As part of this project, we will evaluate a number of plasma estrogens (e.g., estradiol, estrone, estrone sulfate) and other hormones in relation to breast cancer risk in postmenopausal women. However, increasing evidence supports a role for specific estrogen metabolites (e.g., 2-OH and 4-OH estrone and estradiol) in breast cancer etiology. These metabolites are most frequently measured in urine, and their measurement in blood requires large volumes (more than we can reasonably provide with the samples currently being collected). Therefore, the specific aim of the current proposal is to collect and archive a 20ml urine sample from each of the 18,169 women for whom we are currently funded to collect a blood sample. This will allow us to evaluate prospectively the relationship between urinary estrogen metabolites and breast cancer risk, and, eventually to evaluate other hypotheses (e.g., estrogen metabolites and endometrial cancer risk, phytoestrogen levels and cancer risk). In this application, we are only requesting funds to collect and store urine samples -- we are not requesting funds for laboratory analysis of the samples. Because the blood sample collection among the 18,169 women is already funded, the additional cost of collecting and storing a urine sample is small. Additionally, the application meets the requirements of an R03 in that the funding will be used to plan a complex epidemiologic investigation. We believe this is a unique opportunity to collect and archive urine samples, at a very reasonable cost, that will allow for future prospective assessments of several very important issues related to hormones and breast cancer risk.