Sedentary Behavior and Breast Cancer: Interventions and Biomarkers

描述（由申请人提供）：这份K07提案详细介绍了培训活动、指导和研究项目的综合计划，这些计划将为我提供支持、知识和技能，使我成为一名专注于久坐行为和乳腺癌的独立研究者。正如我的教育背景、出版历史和研究活动所证明的那样，我致力于健康行为、肥胖、癌症预防和生存领域。我在耶鲁大学获得流行病学和心理学博士学位，并在弗雷德·哈钦森癌症研究中心完成了生物行为癌症预防和控制的博士后研究。我从2009年开始在加州大学圣地亚哥分校（UCSD）的摩尔癌症中心进行研究，并于2013年被任命为UCSD家庭和预防医学系助理教授。完成这项K07将有助于我向独立研究者的过渡，并使我成为久坐行为和癌症领域的领导者。久坐行为在生理和行为上都不同于体育活动，是一个新兴的研究领域，引起了癌症界越来越大的兴趣。关于久坐对健康不利影响的研究进展迅速，最近的数据显示，客观测量的久坐时间与乳腺癌风险增加有关。需要更多的研究来了解久坐时间与乳腺癌之间的关系，并确定减少久坐时间是否可以降低风险和/或提高生存率。拟议的培训计划将使我获得以下方面的高级知识和技能：(1)久坐行为干预的发展，(2)使用已建立和新兴的方法评估久坐行为，(3)将久坐和活动行为与癌症联系起来的生物学机制，(4)分析久坐和活动数据的高级统计，以及(5)领导能力，拨款撰写和职业发展。加州大学圣地亚哥分校是实现这些目标的理想环境，因为它拥有非常强大的生活方式和癌症研究团队，新成立的关注久坐行为和健康的兴趣小组，以及nci资助的能量学和癌症跨学科研究（TREC）中心。我的主要导师是贝丝·马库斯博士，共同导师则是。西蒙·马歇尔和露丝·帕特森。马库斯博士是加州大学圣地亚哥分校家庭和预防医学的主席，在过去的25年里一直获得美国国立卫生研究院的资助，并且在指导初级教师方面有着出色的记录。马歇尔博士是加州大学圣地亚哥分校家庭和预防医学副教授，在久坐行为研究方面具有专长，并指导了100多名学生、研究员和初级教师。Patterson博士是加州大学圣地亚哥分校TREC中心的PI，在癌症生物标志物方面拥有专业知识。顾问将确保我在久坐行为评估（Jacqueline Kerr博士）、久坐行为与癌症之间的生物机制（Neville Owen博士）和高级统计学（Loki Natarajan博士）领域实现培训和研究目标。拟议的研究包括两个不同但互补的活动。在第一个目标中，我将进行一项试点研究，研究减少久坐行为的干预措施。目的2使用来自加州大学圣地亚哥分校TREC中心的数据来检查久坐行为与癌症相关生物标志物的关系。目的1（原始研究）：在60名绝经后乳腺癌幸存者中进行2x2随机对照试验，以确定两种干预策略减少客观测量的久坐行为的可行性。具体来说，我将研究(1)短暂的“站立休息”来打断长时间的久坐时间，(2)总体减少25%的久坐时间，(3)两者结合，(4)日常护理。目的2 （TREC数据分析）：通过对340名超重/肥胖乳腺癌幸存者进行调查，研究减少久坐行为对癌症相关的潜在益处，行为减肥干预对久坐行为的影响（干预中特别针对久坐行为）。我们还将研究久坐行为的改变是否会介导干预对生物标志物结果的影响（即胰岛素抵抗、慢性炎症和性激素的标志物）。目的1将提高我设计和实施试点试验的技能，研究结果将为减少乳腺癌幸存者的久坐时间提供见解。Aim 2将增加我对生物标志物的理解，提高我的统计和写作技能，并提供关于客观测量的久坐时间与癌症相关生物标志物之间关系的新数据。综上所述，拟议目标的结果将为检验久坐行为干预对与乳腺癌预后相关的循环生物标志物的积极影响的有效性的试验提供R01建议。如果获得资金，K07将在此基础上进行建设

DESCRIPTION (provided by applicant): This K07 proposal details a comprehensive program of training activities, mentorship, and research projects that will provide me with the support, knowledge, and skills to launch a career as an independent investigator focused on sedentary behavior and breast cancer. As demonstrated by my educational background, publication history, and research activities, I am dedicated to the field of health behavior, obesity, and cancer prevention and survivorship. I received my Ph.D. in Epidemiology and Psychology from Yale University and completed a postdoctoral fellowship in biobehavioral cancer prevention and control at the Fred Hutchinson Cancer Research Center. I have been conducting research at the Moores Cancer Center at the University of California, San Diego (UCSD) since 2009 and was appointed as Assistant Professor within the UCSD Department of Family and Preventive Medicine in 2013. Completion of this K07 will facilitate my transition to an independent investigator and position me to become a leader in the field of sedentary behavior and cancer. Sedentary behavior, which is physiologically and behaviorally distinct from physical activity, is an emerging area of research that is of growing interest to the cancer community. Research on the adverse health effects of excessive sitting is advancing quickly, with recent data showing that objectively-measured sedentary time is associated with increased breast cancer risk. More research is needed to understand the relationship between sedentary time and breast cancer and to determine whether reducing sedentary time could lower risk and/or improve survival. The proposed training plan will allow me to gain advanced knowledge and skills in: (1) development of sedentary behavior interventions, (2) assessment of sedentary behavior using established & emerging methods, (3) biological mechanisms linking sedentary and active behaviors with cancer, (4) advanced statistics for analysis of sedentary and activity data, and (5) leadership, grant-writing, and career development. UCSD is the ideal environment in which to pursue these goals due to its exceptionally strong group of lifestyle and cancer researchers, the availability o newly-formed interest groups focused on sedentary behavior and health, and the presence of an NCI-funded Transdisciplinary Research on Energetics and Cancer (TREC) Center. My primary mentor will be Dr. Bess Marcus, with co-mentorship provided by Drs. Simon Marshall and Ruth Patterson. Dr. Marcus is Chair of Family and Preventive Medicine at UCSD, has had continuous NIH funding for the past 25 years, and has an excellent track record of mentoring junior faculty. Dr. Marshall is Associate Professor of Family and Preventive Medicine at UCSD, has expertise in sedentary behavior research, and has mentored over 100 students, fellows, and junior faculty. Dr. Patterson is the PI of the UCSD TREC Center and has expertise in cancer biomarkers. Consultants will ensure that I achieve my training and research goals in the areas of sedentary behavior assessment (Dr. Jacqueline Kerr), biologic mechanisms linking sedentary behavior with cancer (Dr. Neville Owen), and advanced statistics (Dr. Loki Natarajan). The proposed research includes 2 distinct, but complementary activities. For Aim 1, I will conduct a pilot study examining interventions to reduce sedentary behavior. Aim 2 uses data from the UCSD TREC Center to examine the association of sedentary behavior with cancer-related biomarkers. Aim 1 (original research): To conduct a 2x2 randomized controlled pilot trial among 60 postmenopausal breast cancer survivors to determine the feasibility of 2 intervention strategies for reducing objectively- measured sedentary behavior. Specifically, I will examine (1) brief "standing breaks" to interrupt long bouts of sedentary time, (2) overall 25% reduction in sedentary time, (3) both in combination, and (4) usual care. Aim 2 (analysis of TREC data): To investigate the potential cancer-relevant benefits of reducing sedentary behavior by examining, among 340 overweight/obese breast cancer survivors, the effects of a behavioral weight loss intervention on sedentary behavior (which is specifically targeted in the intervention). We will also examine whether changes in sedentary behavior mediate the impact of the intervention on biomarker outcomes (i.e. markers of insulin resistance, chronic inflammation, and sex hormones). Aim 1 will enhance my skills in designing and conducting a pilot trial, and study findings will provide insight on reducing sedentary time among breast cancer survivors. Aim 2 will increase my understanding of biomarkers, enhance my statistical and writing skills, and provide novel data on the association of objectively measured sedentary time with cancer-related biomarkers. Taken together, the results of the proposed aims will inform an R01 proposal for a trial examining the efficacy of a sedentary behavior intervention to positively impact circulating biomarkers related to breast cancer prognosis. If funded, this K07 will build on my previous experience in physical activity while taking my career in an exciting new direction focused on sedentary behavior.