Investigating the Role of a Lifestyle Intervention on Novel Estrogen Biomarkers

研究生活方式干预对新型雌激素生物标志物的作用

• 批准号: 8704132
• 负责人: Kerryn W Reding
• 金额: $ 23.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-19 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8704132
• 关键词: Adherence; Age; Applications Grants; Award; Behavior; Behavior Therapy; Behavioral Research; Binding; Biological; Biological Markers; Biology; Biomarker of Dietary Intake; Body Composition; Body fat; Breast; Cardiovascular Diseases; Catechol Estrogens; Chronic Disease; Clinic; Clinical; Cognitive Therapy; Control Groups; Coupled; Cross-Sectional Studies; DNA Adducts; Data; Demographic Factors; Development; Diabetes Mellitus; Diet; Diet Modification; Dietary Factors; Eligibility Determination; Endometrial; Endometrial Carcinoma; Enrollment; Ensure; Epidemiology; Equilibrium; Estrogen Metabolism; Estrogens; Exercise; Exhibits; Faculty; Fatty acid glycerol esters; Feasibility Studies; Fostering; Gene Mutation; Goals; Growth; Habits; Health Promotion; Institutes; Intervention; Intervention Studies; Intervention Trial; Lead; Life Style; Light; Literature; Malignant Neoplasms; Mentors; Methods; Movement; National Institute of Nursing Research; Nurses; Nursing Research; Participant; Pathway interactions; Patients; Persons; Phase; Physical activity; Pilot Projects; Population; Population Study; Positioning Attribute; Primary Health Care; Quinones; Recruitment Activity; Reporting; Research; Research Personnel; Research Project Grants; Risk; Role; Sample Size; Staging; Target Populations; Testing; Time; Training; Treatment Efficacy; Urine; Woman; Work; adduct; base; biobehavior; carcinogenesis; career; career development; design; diet and exercise; experience; fruits and vegetables; group intervention; high risk; improved; intervention effect; lifestyle intervention; malignant breast neoplasm; novel; response; sedentary; therapy design

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.

研究生活方式干预对新型雌激素生物标志物的作用 抽象的 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) 醌能够形成 DNA 加合物，在某些情况下可能导致 DNA 突变。 因此，HE 醌参与致癌作用的生物学合理性 再加上 CE 代谢是可逆的这一事实表明该途径非常适合靶向 干预研究。除了这项研究与国家护理研究所保持一致外 研究重点是生物学和行为的整合，及其阐明可改变因素的潜力 涉及 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：具有研究儿茶酚雌激素途径的背景 从流行病学的角度来看，雷丁博士建议接受行为和护理研究方面的培训，以便 在临床环境中采用认知行为疗法 (CBT) 方法实施干预。 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，并采取久坐的生活方式，开始改变以改善饮食和 增加他们的体力活动。除了指导阶段的正式培训外，申请人还将获得 现有 CBT 干预研究中的研究经验，并使用 125 来自特征明确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) 及其未结合的对应物（具体目标 1）。期间 独立阶段，候选人将进行可行性研究，以确定其可行性 在目标人群中实施生活方式干预（具体目标 2），确定 该人群的生物标志物（具体目标 3）并探索干预措施对身体的影响 组成（具体目标 4）。结果：试点和可行性研究的结果将用于提供 R01 应用程序的初步数据，旨在调查饮食和运动的假设 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奖励机制将通过使雷丁博士能够 候选人发展新研究方向的专业知识，即实施行为学 基于临床干预，以实现她获得教职职位的长期职业目标 她将能够启动一项独立的研究，调查生活方式干预措施的影响 关于生物学机制。