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

项目摘要/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，黑人妇女正在经历着最显著的增长。众所周知，肥胖 与任何其他癌症相比，增加EC风险的作用更大。随着肥胖率的持续上升，肥胖的负担 EC也将增长，强调需要有效的初级预防战略。关于可逆性的证据 通过减肥带来的食典性食典委风险正在显现。为了有效地干预以降低欧共体风险，我们必须确定 体重减轻和较低的EC风险之间的联系的生物学机制。的主要目标 这项建议是为了研究减肥后身体成分的变化如何影响炎症 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与黑人不同 还有白人女性。炎症与过度肥胖有关，并与发生EC的更高风险有关。 申请者将进行一项试点队列研究，招募40名黑人和40名白人妇女通过医学检查，并 计划接受减肥手术，20名黑人和20名白人女性参加非手术减肥 程序(控制)。在基线时，我们将通过问卷调查评估EC危险因素，测量身体成分 使用双X射线吸收测量仪(DXA)进行子宫内膜组织活检和采血以寻找生物标志物 子宫内膜增生症(EH)的特征和评估，这是一种EC的前驱病变，使用病理学回顾 (目标1)。手术或非手术减肥干预6个月后，我们将测量身体成分。 以及组织和血清中的炎症来评估减肥后的变化(目标2)，我们将探索种族 基线关系和时间依赖关系的差异(目标3)。此K01应用程序的调查结果将增加 我们对过度肥胖对局部炎症和肿瘤发生的影响的理解 并通过使用DXA提供更高分辨率的肥胖症数据 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，并产生了新的假说，关于食典委预防。除了一条新的研究路线外， 申请人提出明确的培训计划，这对申请人获得主题至关重要。 适用于拟议研究的专业知识和熟练程度。申请人将接受以下方面的培训：设计 和进行前瞻性流行病学和临床研究；健康差异研究；身体成分； 肥胖与癌症生物学；干预研究进展；纵向数据分析；翻译 研究；以及生物信息学分析。这项培训将通过课程作业、参加 研讨会、研讨会、会议，以及最重要的是，来自高度合格的 由导师和合作者组成的团队，体现了多种学科。强化训练计划和创新 这份K01申请中概述的研究将为申请者成功过渡到独立的 研究人员将重点放在肥胖与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.