Endocrine disrupting chemicals and risk of uterine fibroids: a prospective study

内分泌干​​扰化学物质与子宫肌瘤的风险：一项前瞻性研究

• 批准号: 8963998
• 负责人: LAUREN A WISE
• 金额: $ 67.43万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8963998
• 关键词: African; African American; Age; Animals; Binding; Biological Markers; Blood; Body mass index; Centers for Disease Control and Prevention (U.S.); Characteristics; Chemical Exposure; Chemicals; Cohort Studies; Communities; Contraceptive Usage; Data; Data Collection; Diagnosis; Endocrine Disruptors; Endocrine system; Environment; Epidemiologic Studies; Estrogens; Etiology; Exposure to; Fibroid Tumor; Gonadal Steroid Hormones; Gynecologic; Health; Health Care Costs; Health Services Research; High Prevalence; Hormone Receptor; Hormones; Human; Hysterectomy; In Vitro; Incidence; Individual; Infertility; Laboratories; Laboratory Study; Life Style; Link; Location; Measurement; Measures; Menorrhagia; Methods; Morbidity - disease rate; National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences; Oral Contraceptives; Participant; Pelvic Pain; Phenols; Policy Maker; Polychlorinated Biphenyls; Population; Pregnancy Complications; Prevalence; Production; Progesterone; Prospective Studies; Questionnaires; Reproductive Process; Research; Research Design; Research Infrastructure; Research Priority; Risk; Risk Factors; Sample Size; Sampling; Serum; Severity of illness; Source; Symptoms; Testing; Time; Training; Ultrasonography; United States; United States National Institutes of Health; Urine; Uterine Fibroids; Woman; Women' s Health; aged; base; bisphenol A; case control; chemical association; clinically significant; cost; cost effective; design; disorder prevention; health care quality; high risk; human data; innovation; parity; phthalates; pollutant; prospective; public health relevance; racial disparity; reproductive; reproductive hormone; reproductive morbidity; screening; tumor; urinary

 DESCRIPTION (provided by applicant): Uterine leiomyomata (UL) are diagnosed in 25-30% of reproductive-aged women, resulting in considerable gynecologic morbidity and billions in U.S. health care costs annually. African Americans have 2-3 times the UL incidence of Whites and greater disease severity. Sex steroid hormones are involved in the etiology of UL. Given that endocrine disrupting chemicals (EDCs) can alter the functioning of hormones, we propose to evaluate UL risk in relation to 3 classes of EDCs: phthalates, polychlorinated biphenyls (PCBs), and phenols, specifically bisphenol A (BPA). Our choice of chemicals is informed by their high exposure prevalence in humans and by in vitro, animal, and human data documenting their effects on reproductive hormones and processes that could influence UL risk. Existing studies of EDCs and UL are limited by small sample size, uncertain temporality due to retrospective design, and suboptimal measurement of EDCs and UL. This study will use data and biospecimens from the Study of Environment Lifestyle and Fibroids (SELF), a NIEHS prospective cohort study of 1,300 African American women aged 23-34 and free of UL at baseline (2010-2012). Questionnaire data were collected at baseline and subjects are being followed for 5 years. Every 20 months, blood and urine are collected, and ultrasounds are performed by trained sonographers to detect UL. We request support for the laboratory and statistical analysis of EDCs in relation to UL incidence. We propose a cost-effective case-cohort study design that includes 400 incident UL cases and 400 controls. We will measure urinary phthalate metabolites, serum PCBs, and urinary BPA, characterize exposures according to UL risk factors, and determine the associations of these chemicals with UL incidence and tumor characteristics. Non-persistent chemicals (phthalates, BPA) will be measured at baseline, 20 months, and 40 months. Persistent chemicals (PCBs) will be measured at baseline only. SELF provides a unique opportunity to assess the association of common EDCs with UL risk. This project has many strengths that overcome the limitations of prior studies: large sample size, prospective data collection, state-of-the-art EDC measurement, serial ultrasound screening for UL, analysis of repeated EDC measures, innovative statistical approaches for evaluating EDC mixtures, and control for multiple confounders. Pilot data show large exposure variability, providing excellent power to test the proposed hypotheses. This study of African Americans, a high-risk population for EDC exposure and UL, will provide informative data on the effects of widespread pollutants on UL, seek explanations for the racial disparity in UL incidence, and provide critical data to the public, scientific community, and policy makers.

 描述（由申请人提供）：子宫平滑肌瘤（UL）在25-30%的育龄妇女中被诊断出来，导致相当多的妇科疾病发病率和美国每年数十亿美元的医疗保健费用。非裔美国人的UL发病率是白人的2-3倍，疾病严重程度更高。性类固醇激素参与UL的病因学。鉴于内分泌干扰物（EDCs）可以改变激素的功能，我们建议评估与3类EDCs相关的UL风险：邻苯二甲酸酯，多氯联苯（PCBs）和苯酚，特别是双酚A（BPA）。我们对化学品的选择是基于其在人类中的高暴露率以及记录其对生殖激素和可能影响UL风险的过程的影响的体外、动物和人类数据。现有的EDCs和UL研究受到样本量小、回顾性设计导致的不确定暂时性以及EDCs和UL测量不佳的限制。本研究将使用来自环境生活方式和纤维瘤研究（SELF）的数据和生物标本，这是一项NIEHS前瞻性队列研究，研究对象为1，300名年龄在23-34岁之间的非洲裔美国女性，基线时无UL（2010-2012）。在基线时收集问卷数据，并对受试者进行5年随访。每20个月，收集血液和尿液，并由受过训练的超声波检查员进行超声波检查，以检测UL。我们请求支持与UL发生率相关的EDCs的实验室和统计分析。我们提出了一个具有成本效益的病例队列研究设计，包括400例UL事件和400例对照。我们将测量尿邻苯二甲酸酯代谢物、血清PCB和尿BPA，根据UL风险因素描述暴露特征，并确定这些化学物质与UL发病率和肿瘤特征的关联。将在基线、20个月和40个月时测量非持久性化学物质（邻苯二甲酸盐、BPA）。持久性化学品（PCB）将仅在基线进行测量。SELF提供了一个独特的机会来评估常见的内分泌干扰物与UL风险的关联。该项目具有许多优势，克服了先前研究的局限性：大样本量，前瞻性数据收集，最先进的EDC测量，UL的连续超声筛查，重复EDC测量的分析，用于评估EDC混合物的创新统计方法，以及控制多种混杂因素。试点数据显示，大的曝光可变性，提供了很好的力量来检验所提出的假设。这项对非裔美国人（EDC暴露和UL的高风险人群）的研究将提供有关广泛污染物对UL影响的信息数据，寻求UL发病率种族差异的解释，并为公众，科学界和政策制定者提供关键数据。