Premonopausal Hormone Levels and Risk of Breast Cancer

描述（由研究者提供）：本申请是R01 CA67262的竞争性修订，标题为“绝经前激素水平和乳腺癌风险”，响应no - od -09-058，“竞争性修订申请的恢复法案资金的可用性”。在护士健康研究II （NHSII）队列中，父母赠款用于评估一系列绝经前激素（如血浆性类固醇）与乳腺癌风险的关系。NHSII队列包括116,430名妇女，自1989年以来每两年进行一次问卷调查。在1996年至1999年间（由CA67262资助），我们收集了29,611名NHSII参与者的血液和尿液样本。在目前的应用中，我们建议从这些女性身上收集第二组血液和尿液样本，这将大大提高在生命不同阶段检测与癌症风险相关的生物标志物的能力。第一次收集的女性年龄在32 - 54岁之间，主要是绝经前；他们将在46至66岁之间，在建议收集时主要是绝经后。从NHSII妇女身上收集的第二组生物标本将形成世界上唯一一个从10-15岁的同一妇女身上收集样本的大型生物库之一；根据之前的生物标本收集反应率，我们预计将从19,000多名妇女中获得样本。此外，许多样本集将配对绝经前和绝经后的样本（n~13,000名妇女）。随着该队列的持续随访，我们将处于一个独特的位置，以评估生物标志物与疾病风险之间的时间关联，鉴于其多阶段的致癌过程，这与癌症特别相关。此外，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志物-疾病关系中的重要性。此外，对乳腺癌研究的重大兴趣在于绝经前和绝经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。该应用程序通过雇用三名新员工，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返回的样本，从而满足了《美国复苏与再投资法案》的目标。最终，这一资源将导致未来拨款的科学目标的发展，这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的支持，并为研究生物标志物与妇女疾病之间的关系创建一个强大的生物库。

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.