Premonopausal Hormone Levels and Risk of Breast Cancer

描述(由研究人员提供)：本申请是对R01 CA67262的竞争性修订，标题为“绝经前激素水平和乳腺癌风险”，以回应NOT-OD-09-058，“恢复法案资金的可用性，用于竞争性修订申请”。父母拨款资助护士健康研究II(NHSII)队列中与乳腺癌风险相关的一系列绝经前激素(例如，血浆性类固醇)的评估。NHSII队列由116,430名女性组成，她们自1989年以来每两年接受一次问卷调查。在1996至1999年间(由CA67262资助)，我们收集了29,611名NHSII参与者的血液和尿样。在目前的应用中，我们建议从这些女性身上收集第二套血液和尿液样本，这将大大增强检查生命中不同时间点的生物标记物暴露与癌症风险的能力。第一次收集时，女性年龄在32岁至54岁之间，以绝经为主；她们将在46岁至66岁之间，在拟议收集时以绝经后为主。从NHSII妇女身上收集第二套生物检验剂将形成世界上仅有的具有相隔10-15年的相同妇女样本的大型生物库之一；我们预计根据先前的生物检验剂收集响应率，将从19,000多名妇女那里获得样本。此外，许多样本集将是绝经前和绝经后样本(n~13,000名妇女)的配对。随着队列的持续跟踪，我们将处于一个独特的位置来评估生物标记物和疾病风险之间的时间相关性，鉴于癌症的多阶段致癌过程，疾病风险与癌症具有特别的相关性。此外，拥有一个中年样本和一个晚年样本将有助于确定年龄在改变生物标记物-疾病关系中的重要性。此外，在乳腺癌研究中，人们非常感兴趣的是绝经前后测量的内源性激素是否与乳腺癌风险独立相关，以及两者之间是否存在潜在的相互作用。该应用程序通过招聘三名新员工，从一家美国公司购买设备，并使用另一家美国公司邮寄血液采集试剂盒并处理退回的样本，从而满足了美国复苏和再投资法案的目标。最终，这一资源将导致为未来的拨款制定科学目标，这些目标将解决重要的科学问题，创造新的就业机会，为现有人员提供持续支持，并创建一个强大的生物信息库，用于研究生物标记物与妇女疾病之间的联系。 与公共卫生相关：该项目将在护士健康研究II中创建一个血液和尿液储存库，其中包含相隔大约10到15年收集的相同女性的样本，其中近70%将是绝经前和绝经后的样本配对。这一资源可用于回答与生物标记物暴露和癌症风险有关的重要科学问题，以更好地了解癌症是如何发展的，并确定潜在的预防方法。

DESCRIPTION (provided by investigator): This applications is a Competitive Revision to R01 CA67262, entitled "Premenopausal Hormone Levels and Risk of Breast Cancer", in response to NOT-OD-09-058, "The Availability of Recovery Act Funds for Competitive Revision Applications". The parent grant funds the assessment of a range of premenopausal hormones (e.g., plasma sex steroids) in relation to breast cancer risk in the Nurses' Health Study II (NHSII) cohort. The NHSII cohort consists of 116,430 women who have been followed biennially by questionnaire since 1989. Between 1996 and 1999 (and funded by CA67262), we collected blood and urine samples from 29,611 NHSII participants. In the current application, we propose to collect a second set of blood and urine samples from these women, which will substantially enhance the ability to examine biomarker exposures at different points in life in relation to cancer risk. Women were 32 to 54 years old at the first collection and were predominantly premenopausal; they will be 46 to 66 years old and predominantly postmenopausal at the time of the proposed collection. The collection of a second set of biospecimens from NHSII women would form one of the only large biorepository in the world to have samples from the same women 10-15 years apart; we anticipate based on prior biospecimen collection response rates to obtain samples from over 19,000 women. Further, many of the sample sets would be paired pre- and postmenopausal samples (n~13,000 women). With continued follow-up of the cohort, we would be in a unique position to assess temporal associations between biomarkers and disease risk, which has particular relevance to cancer given its multi-stage carcinogenic process. In addition, having a mid-life sample and a sample in later life will assist in determining the importance of age in modifying biomarker-disease relationships. Further, of substantial interest in breast cancer research is whether endogenous hormones measured during pre- and post menopause are independently associated with breast cancer risk, and whether potential interactions exist between the two. This application meets the goals of the American Recovery and Reinvestment Act by hiring three new staff members, purchasing equipment from a U.S. company, and using another U.S. company to mail blood collection kits and process the returned samples. Ultimately, this resource would lead to the development of scientific aims for future grants that would address important scientific questions, create new jobs, provide continuing support for existing personnel, and create a powerful biorepository for studying associations between biomarkers and disease in women. PUBLIC HEALTH RELEVANCE: This project would create a blood and urine repository in the Nurses' Health Study II containing samples from the same women collected about 10 to 15 years apart, nearly 70 percent of which would be paired pre- and postmenopausal samples. This resource could be used to answer important scientific questions relating to biomarker exposures and cancer risk, to better understand how cancer develops and identify potential prevention methods.