Investigating the Role of a Lifestyle Intervention on Novel Estrogen Biomarkers

调查生活方式干预对新型雌激素生物标志物的作用 摘要 背景：大量证据表明雌激素与乳腺癌和子宫内膜癌有关 发展儿茶酚雌激素（CE）途径中的雌激素代谢物，特别是羟基雌激素 (HE)醌类能够形成DNA加合物，在某些情况下可导致DNA突变。 因此，HE醌类参与致癌起始的生物学可能性 再加上CE代谢是可逆的这一事实表明，该途径是理想的靶向在一个 干预研究除了这项研究与国家护理研究所保持一致外， 研究的重点是整合生物学和行为，以及阐明可改变因素的潜力 参与CE途径，该项目还允许候选人获得培训，以发展成为 独立研究员。方法：以邻苯二酚雌激素通路为背景， 从流行病学的角度来看，雷丁博士建议获得行为和护理研究的培训，以 实施基于临床环境的采用认知行为疗法（CBT）方法的干预。 生活方式干预将侧重于激励来自初级保健诊所的高风险患者， 乳腺癌和/或子宫内膜癌，并导致久坐的生活方式，以开始改变，以改善他们的饮食， 增加他们的体力活动。除了在辅导阶段接受正式培训外，申请人还将获得 在现有的CBT干预研究的研究经验，以及进行试点研究，使用125 来自充分表征的现有研究人群的女性，以表征新的生物标志物， 即羟基雌激素结合加合物（HEBA）和它们的未结合对应物（特异性目标1）。期间 在独立阶段，候选人将进行可行性研究，以确定 在目标人群中实施生活方式干预（具体目标2），确定 该人群中的生物标志物（具体目标3），并探索干预对身体的影响 具体目标（4）。结果：试点和可行性研究的结果将用于提供 R 01应用程序的初步数据，该应用程序建议调查饮食和运动 干预可以影响CE途径中代谢物的平衡，特别关注新的 生物标志物。结论：K99奖励机制将促进雷丁博士的职业发展， 候选人在一个新的研究方向发展的专业知识，即在实施行为 基于临床干预，以达到她的长期职业目标，实现教师职位， 她将能够发起一项独立的研究，调查生活方式干预的影响， 生物机制。

Investigating the Role of a Lifestyle Intervention on Novel Estrogen Biomarkers ABSTRACT Background: There is a large accumulation of evidence implicating estrogen in breast and endometrial cancer development. Estrogen metabolites within the catechol estrogen (CE) pathway, in particular hydroxy estrogen (HE) quinones, are capable of forming DNA adducts which may lead in certain instances to DNA mutations. Thus, the biological plausibility of the involvement of the HE quinones in the initiation of carcinogenesis coupled with the fact that CE metabolism is reversible indicates that this pathway is ideal for targeting in an intervention study. In addition to this research being well aligned with the National Institute of Nursing Research's focus on integrating biology and behavior, and its potential for elucidating modifiable factors involved the CE pathway, this project also allows for the candidate to gain training in order to develop into an independent researcher. Methods: Having a background studying the catechol estrogen pathway from an epidemiologic perspective, Dr. Reding proposes to gain training in behavioral and nursing research in order to implement an intervention employing a cognitive behavioral therapy (CBT) approach based in a clinical setting. The lifestyle intervention will focus on motivating patients from primary care clinics who are at a high risk for breast and/or endometrial cancer and leading a sedentary lifestyle to initiate changes to improve their diet and increase their physical activity. In addition to formal training during the mentored phase, the applicant will gain research experiences within existing studies of CBT interventions, as well as conduct a pilot study using 125 women from a well-characterized, existing study population in order to characterize the novel biomarkers, namely hydroxy estrogen bound-adducts (HEBA) and their unbound counterparts (Specific Aim 1). During the independent phase, the candidate will implement a feasibility study in order to identify the practicability of implementing a lifestyle intervention within the target population (Specific Aims 2), determine the variability of the biomarker in this population (Specific Aim 3) and explore the impact of the intervention on body composition (Specific Aim 4). Results: The results from the pilot and feasibility studies will be used to provide preliminary data for an R01 application proposing to investigate the hypothesis that a diet and exercise intervention can impact the balance of metabolites in the CE pathway with a particular focus on novel biomarkers. Conclusion: The K99 award mechanism will foster Dr. Reding's career growth by enabling the candidate to develop expertise in a new direction of research, namely in the implementation of behaviorally based clinical interventions, in order to reach her long-term career goals of attaining a faculty position where she would be able to launch an independent line of research investigating the impact of lifestyle interventions on biological mechanisms.