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.

项目摘要/摘要 在美国（美国），所有种族的妇女中的子宫内膜癌（EC）的发病率正在增加 亚组；但是，黑人妇女正在经历最大的增长。众所周知肥胖 比任何其他癌症都会增加EC风险。随着肥胖症的患病率继续上升， EC还将增长，强调需要有效的初级预防策略。有关可逆性的证据 通过减肥的EC风险正在出现。为了有效干预以降低EC风险，我们必须确定 体重减轻和降低EC风险之间关联的生物学机制。主要目标 该提议是研究体重减轻后身体成分的变化如何影响炎症 活检回收的子宫内膜组织和血清中的生物标志物以及黑色之间的这些过程是否有所不同 和白人妇女。炎症与过量肥胖有关，并与较高的EC风险相关。 申请人将进行一项试验队列研究，招收40名黑人和40名白人妇女的医学清理和 计划进行减肥手术，并参加20名黑人和20名白人妇女参加非手术减肥 程序（控件）。在基线时，我们将通过问卷调查，测量身体成分来评估EC风险因素 使用双X射线吸收法（DXA），进行子宫内膜组织活检和血液用于生物标志物 使用病理综述，表征并评估EC前体病变的子宫内膜增生（EH）（EH） （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，以评估体重减轻后的变化（AIM 2），我们将探索种族 基线和时间相关关系的差异（AIM 3）。该K01申请的发现将增加 我们对过量肥胖对局部炎症和癌症开始的影响的理解 子宫内膜环境，并通过使用DXA提供更高的分辨率数据 以前仅使用体重指数的研究。此外，这项研究将添加有关种族差异的新数据 这些过程并产生有关EC预防的新假设。除了一项新的研究系列， 申请人提出了一个明确定义的培训计划，以便申请人获得主题。 适用于拟议的研究的专业知识和熟悉度。申请人将接受培训：设计 并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 研究;和生物信息学分析。该培训将通过课程工作，参加 讲习班，研讨会，会议，最重要的是，来自高素质的动手指导研究 导师和合作者团队，反映了多个学科。密集培训计划和创新 本K01申请中概述的研究将使申请人成功地过渡到独立 研究人员专注于肥胖-EC风险关系的基础的分子机制。

项目成果

Cancer Progress and Priorities: Uterine Cancer.

• DOI: 10.1158/1055-9965.epi-18-0264
• 发表时间: 2018-09
• 期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
• 作者: Felix AS;Brinton LA
• 通讯作者: Brinton LA

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。

• DOI: 10.1136/ijgc-2019-000728
• 发表时间: 2019
• 期刊: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
• 作者: Zhang,Xiaochen;Rhoades,Jennifer;Caan,BetteJ;Cohn,DavidE;Salani,Ritu;Noria,Sabrena;Suarez,AdrianA;Paskett,ElectraD;Felix,AshleyS
• 通讯作者: Felix,AshleyS

Where you live matters: A National Cancer Database study of Medicaid expansion and endometrial cancer outcomes.

• DOI: 10.1016/j.ygyno.2020.05.018
• 发表时间: 2020-08
• 期刊: Gynecologic oncology
• 影响因子: 4.7
• 作者: Barrington DA;Sinnott JA;Calo C;Cohn DE;Cosgrove CM;Felix AS
• 通讯作者: Felix AS

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

• DOI: 10.1016/j.jmig.2021.07.018
• 发表时间: 2022-03
• 期刊: Journal of minimally invasive gynecology
• 影响因子: 4.1
• 作者: Bixel K;Barrington DA;Vetter MH;Suarez AA;Felix AS
• 通讯作者: Felix AS

The association between histological subtype of a first primary endometrial cancer and second cancer risk.

第一原发性子宫内膜癌的组织学亚型与第二癌症风险之间的关联。

• DOI: 10.1136/ijgc-2018-000014
• 发表时间: 2019
• 期刊: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
• 作者: Rhoades,Jennifer;Vetter,MonicaHagan;Fisher,JamesL;Cohn,DavidE;Salani,Ritu;Felix,AshleyS
• 通讯作者: Felix,AshleyS