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: 7950398
• 负责人: Kerryn W Reding
• 金额: $ 8.95万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950398
• 关键词: Adherence; Age; Applications Grants; Award; Behavior; Behavior Therapy; Behavioral; Binding; Biological; Biological Markers; 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 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; public health relevance; response; sedentary; therapy design

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: With the main goal of this career development proposal being to prepare the candidate to conduct interventions aimed at improving women's dietary and exercise habits, this proposal is well aligned with the National Institute of Nursing's focus on health promotion, particularly as it relates to the development of interventions designed to sustain healthy behaviors over time. The biobehavioral focus within the current study could help to shed light on how healthy dietary and exercise behaviors reduce the risk of hormonally-related cancers. In addition, a successful lifestyle intervention could also have implications in reducing the risk of multiple chronic diseases, including cardiovascular disease and diabetes.

描述（由申请人提供）：背景：有大量证据积累，暗示雌激素在乳腺癌和子宫内膜癌的发展中。雌激素雌激素（CE）途径中的雌激素代谢产物，尤其是羟基雌激素（He）奎因酮，能够形成DNA加合物，在某些情况下可能导致DNA突变。因此，He Quinones参与致癌作用的生物学合理性以及CE代谢可逆的事实表明，该途径是在干预研究中靶向的理想选择。除了这项研究与美国国家护理研究所（National Surning Research）的关注融合生物学和行为及其阐明可修改因素涉及CE途径的潜力外，该项目还允许候选人获得培训，以发展为独立的研究人员。方法：Reding博士从流行病学的角度研究了Catechol雌激素途径的背景，建议在临床环境中采用认知行为疗法（CBT）方法进行干预，以实施采用认知行为疗法（CBT）方法的干预措施。生活方式干预将集中于激励来自乳腺癌和/或子宫内膜癌高风险的初级保健诊所的患者，并带领久坐的生活方式来开始改变以改善饮食并增加其体育锻炼。除了在指导阶段进行正式培训外，申请人还将在现有的CBT干预研究中获得研究经验，并使用来自一个具有良好表征的现有研究人群的125名妇女进行试点研究，以表征新颖的生物标志物，即雌激素雌激素界限（HEBA）（HEBA）及其未结合的对手（特定的雌激素）（特定的对手）。在独立阶段，候选人将实施可行性研究，以确定目标人群内实施生活方式干预的实用性（具体目标2），确定该人群中生物标志物的可变性（特定目的目标3）并探索干预措施对身体组成的影响（特定目标4）。结果：试点的结果和可行性研究将用于为R01应用提供初步数据，该应用程序提议研究饮食和运动干预可以影响CE途径中代谢物的平衡的假设，并特别关注新型生物标志物。结论：K99奖励机制将通过使候选人能够在新的研究方向发展专业知识来促进Reding博士的职业发展，即在实施基于行为基于行为的临床干预措施方面，以实现她的长期职业目标，以达到达到教师职位的长期职业目标，在该职位上，她将能够在研究生物学干预措施上的独立研究中的独立研究。 公共卫生相关性：这项职业发展建议的主要目标是准备候选人进行旨在改善妇女饮食和运动习惯的干预措施，该提案与国家护理研究所对健康促进的关注良好，尤其是与旨在维持健康行为的开发有关的促进健康。当前研究中的生物行为重点可能有助于阐明饮食和运动行为如何降低与荷尔蒙相关癌症的风险。此外，成功的生活方式干预也可能对降低多种慢性疾病（包括心血管疾病和糖尿病）的风险产生影响。