URINARY ESTROGEN METABOLITES AND BREAST CANCER RISK

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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.