Effect of adiposity changes on endometrial tissue and blood biomarkers in women at increased risk for endometrial cancer

项目总结/摘要 在美国，子宫内膜癌（EC）的发病率在所有种族的妇女中都在增加 然而，黑人妇女的增长最为显著。众所周知，肥胖 增加EC风险比任何其他癌症都要多。随着肥胖症的患病率持续上升， EC也将增长，突出表明需要有效的初级预防战略。可逆性证据 通过减肥的EC风险正在出现。为了有效地干预以减少EC风险，我们必须确定 生物学机制是减肥和降低EC风险之间联系的基础。的主要目标 这项建议是为了研究体重减轻后身体成分的变化如何影响炎症反应， 活检收集的子宫内膜组织和血清中的生物标志物，以及这些过程是否在黑 和白色女人。炎症与过度肥胖有关，并与发生EC的风险较高有关。 申请人将进行一项试点队列研究，招募40名黑人和40名白色女性， 计划接受减肥手术，20名黑人和20名白色妇女参加了非手术减肥 程序（控制）。在基线时，我们将通过问卷调查评估EC风险因素，测量身体成分， 使用双X线吸收法（DXA），进行子宫内膜组织活检和抽血，以检测生物标志物 特征，并评估子宫内膜增生（EH），EC前体病变，使用病理学审查 (Aim 1）。手术或非手术减肥干预后六个月，我们将测量身体成分 组织和血清中的炎症，以评估体重减轻后的变化（目标2），我们将探讨种族 基线和时间依赖关系的差异（目标3）。K 01应用程序的结果将增加 我们对过度肥胖对局部炎症和癌症发生的影响的理解， 子宫内膜环境，并通过使用DXA提供更高分辨率的肥胖数据， 以前的研究只使用体重指数。此外，这项研究将增加关于种族差异的新数据， 这些过程，并产生关于EC预防的新假设。除了一个新的研究方向， 申请人提出一个明确的培训计划，对申请人获得主题至关重要 专业知识和专业知识适用于拟议的研究。申请人将接受以下方面的培训： 进行前瞻性流行病学和临床研究;健康差异研究;身体组成; 肥胖和癌症的生物学;干预研究的发展;纵向数据分析;翻译 研究;和生物信息学分析。这项培训将通过课程作业、出席 讲习班，研讨会，会议，最重要的是，从一个高素质的实践指导研究 导师和合作者的团队，反映了多个学科。强化培训计划和创新 本K 01申请中概述的研究将为申请人成功过渡到独立的 研究人员集中在肥胖与EC风险关系的分子机制上。

PROJECT SUMMARY/ABSTRACT In the United States (U.S.), endometrial cancer (EC) incidence is increasing among women of all racial subgroups; however, black women are experiencing the most dramatic increases. It is well known that obesity increases EC risk more so than any other cancer. As the prevalence of obesity continues to rise, the burden of EC will also grow, underscoring the need for effective primary prevention strategies. Evidence on the reversibility of EC risk through weight loss is emerging. To effectively intervene to reduce EC risk, we must identify the biological mechanisms that underlie associations between weight loss and lower EC risk. The primary goals of this proposal are to examine how changes in body composition following weight loss impact inflammatory biomarkers in biopsy-collected endometrial tissue and serum and whether these processes differ between black and white women. Inflammation is linked with excess adiposity and associated with higher risk of developing EC. The applicant will conduct a pilot cohort study enrolling 40 black and 40 white women medically cleared and scheduled to undergo bariatric surgery and 20 black and 20 white women enrolled in a non-surgical weight loss program (controls). At baseline, we will assess EC risk factors with a questionnaire, measure body composition using dual x-ray absorptiometry (DXA), conduct endometrial tissue biopsies and blood draws for biomarker characterizations, and assess endometrial hyperplasia (EH), an EC precursor lesion, using a pathology review (Aim 1). Six months after the surgical or non-surgical weight loss intervention, we will measure body composition and inflammation in tissue and serum to assess changes following weight loss (Aim 2), and we will explore racial differences in baseline and time-dependent relationships (Aim 3). Findings from this K01 application will increase our understanding of the effect of excess adiposity on inflammation and cancer initiation within the local endometrial environment and provide higher resolution data on adiposity through use of DXA as compared with previous studies that only use body mass index. Further, this study will add novel data on racial differences in these processes and generate new hypotheses regarding EC prevention. In addition to a novel line of research, the applicant proposes a well-defined program of training crucial for the applicant to obtain subject-matter expertise and proficiencies applicable to the proposed research. The applicant will receive training in: the design and conduct of prospective epidemiological and clinical studies; health disparities research; body composition; the biology of adiposity and cancer; development of intervention studies; longitudinal data analysis; translational research; and bioinformatics analysis. This training will be achieved through coursework, attendance at workshops, seminars, conferences, and most importantly, hands-on mentored research from a highly qualified team of mentors and collaborators, reflecting multiple disciplines. The intensive training plan and innovative research outlined in this K01 application will prepare the applicant to successfully transition into an independent investigator focused on the molecular mechanisms that underlie the obesity-EC risk relationship.