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

肥胖变化对子宫内膜癌风险增加的女性子宫内膜组织和血液生物标志物的影响

• 批准号: 10376326
• 负责人: Ashley S. Felix
• 金额: $ 13.36万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10376326
• 关键词: Adipose tissue; Affect; Asian; Bioinformatics; Biological; Biological Markers; Biology; Biopsy; Blood; Body Composition; Body Weight decreased; Body fat; Body mass index; Body measure procedure; C-reactive protein; Cancer Burden; Clinical Research; Cohort Studies; Control Groups; Data; Data Analyses; Discipline; Educational workshop; Endometrial; Endometrial Carcinoma; Endometrial Hyperplasia; Enrollment; Environment; Epidemiology; Future; Goals; Health Disparities Research; Hispanic; Incidence; Inflammation; Inflammatory; Interleukin-1 Receptors; Interleukin-6; Intervention; Intervention Studies; Leadership; Lesion; Link; Literature; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Measures; Medical; Mentors; Mentorship; Minority; Mission; Molecular; National Cancer Institute; Obesity; Operative Surgical Procedures; Pathology; Play; Prevalence; Prevention strategy; Primary Prevention; Process; Public Health; Questionnaires; Race; Research; Research Personnel; Resolution; Risk; Risk Factors; Roentgen Rays; Role; Schedule; Serum; Subgroup; Surveys; TNF gene; TNFR-Fc fusion protein; TNFRSF1A gene; Testing; Thinness; Time; Tissues; Training; Training Programs; Translational Research; United States; Visceral; Weight maintenance regimen; Woman; anakinra; antagonist; bariatric surgery; base; black women; cancer epidemiology; cancer health disparity; cancer initiation; cancer prevention; cancer risk; carcinogenesis; career development; design; endometrial cancer prevention; epidemiology study; experience; high body mass index; high risk; innovation; muscle form; novel; premalignant; programs; prospective; racial difference; reduced muscle mass; response; skills; study population; symposium; therapy development; weight loss intervention; weight loss program

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.

项目概要/摘要 在美国（U.S.），各种族女性的子宫内膜癌（EC）发病率均呈上升趋势 亚组；然而，黑人女性的增长最为显着。众所周知，肥胖 与任何其他癌症相比，EC 风险增加得更多。随着肥胖患病率持续上升，人们的负担 EC 也将增长，凸显了有效初级预防策略的必要性。可逆性的证据 减肥带来的 EC 风险正在出现。为了有效干预降低 EC 风险，我们必须确定 减肥与降低 EC 风险之间关联的生物学机制。主要目标 该提案旨在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在黑人之间是否存在差异 和白人妇女。炎症与过度肥胖有关，并与发生 EC 的较高风险相关。 申请人将进行一项试点队列研究，招募 40 名黑人和 40 名白人女性，她们均经过体检并获得批准。 计划接受减肥手术，20 名黑人和 20 名白人女性参加了非手术减肥 程序（控制）。在基线时，我们将通过问卷评估 EC 风险因素，测量身体成分 使用双 X 射线吸收测定法 (DXA)，进行子宫内膜组织活检和抽血以检测生物标志物 表征，并使用病理学检查评估子宫内膜增生 (EH)（一种 EC 前体病变） （目标 1）。手术或非手术减肥干预后六个月，我们将测量身体成分 以及组织和血清中的炎症来评估体重减轻后的变化（目标 2），我们将探讨种族 基线和时间依赖性关系的差异（目标 3）。此 K01 应用程序的调查结果将会增加 我们对过度肥胖对局部炎症和癌症发生的影响的理解 与子宫内膜环境相比，通过使用 DXA 提供更高分辨率的肥胖数据 以前的研究仅使用体重指数。此外，这项研究将添加有关种族差异的新数据 这些过程并产生关于 EC 预防的新假设。除了新颖的研究路线外， 申请人提出了一个明确的培训计划，这对于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 进行前瞻性流行病学和临床研究；健康差异研究；身体成分； 肥胖和癌症的生物学；干预研究的发展；纵向数据分析；翻译的 研究;和生物信息学分析。该培训将通过课程作业、参加 讲习班、研讨会、会议，最重要的是，由高素质人士指导的实践研究 由导师和合作者组成的团队，反映了多个学科。强化培训计划和创新 本 K01 申请中概述的研究将为申请人成功过渡到独立 研究人员专注于肥胖与 EC 风险关系背后的分子机制。

项目成果

The prognostic significance of aortic lymph node metastasis in endometrial cancer: Potential implications for selective aortic lymph node assessment.

子宫内膜癌主动脉淋巴结转移的预后意义：选择性主动脉淋巴结评估的潜在影响。

• 发表时间: 2019
• 影响因子: 4.7
• 作者: Cosgrove, Casey M;Cohn, David E;Rhoades, Jennifer;Felix, Ashley S
• 通讯作者: Felix, Ashley S

Determinants of Surgical Approach and Survival Among Women with Endometrial Carcinoma.

子宫内膜癌女性手术方法和生存的决定因素。

• 发表时间: 2022-02
• 作者: Bixel, Kristin;Barrington, David A;Vetter, Monica H;Suarez, Adrian A;Felix, Ashley S
• 通讯作者: Felix, Ashley S

Black and Hispanic women are less likely than white women to receive guideline-concordant endometrial cancer treatment.

黑人和西班牙裔女性接受符合指南的子宫内膜癌治疗的可能性低于白人女性。

• 发表时间: 2020
• 影响因子: 9.8
• 作者: Kaspers, Mara;Llamocca, Elyse;Quick, Allison;Dholakia, Jhalak;Salani, Ritu;Felix, Ashley S
• 通讯作者: Felix, Ashley S

Cancer Progress and Priorities: Uterine Cancer.

癌症进展和优先事项：子宫癌。

• 发表时间: 2018-09
• 作者: Felix, Ashley S;Brinton, Louise A
• 通讯作者: Brinton, Louise A

Intentional weight loss, weight cycling, and endometrial cancer risk: a systematic review and meta-analysis.

有意减肥、体重循环和子宫内膜癌风险：系统评价和荟萃分析。

• 发表时间: 2019
• 作者: Zhang, Xiaochen;Rhoades, Jennifer;Caan, Bette J;Cohn, David E;Salani, Ritu;Noria, Sabrena;Suarez, Adrian A;Paskett, Electra D;Felix, Ashley S
• 通讯作者: Felix, Ashley S