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）：25-30% 的育龄妇女被诊断出子宫平滑肌瘤 (UL)，导致相当大的妇科发病率和每年数十亿美元的美国医疗保健费用。非裔美国人的 UL 发病率是白人的 2-3 倍，且疾病严重程度更高。性类固醇激素与 UL 的病因有关。鉴于内分泌干扰化学品 (EDC) 可以改变激素的功能，我们建议评估与 3 类 EDC 相关的 UL 风险：邻苯二甲酸盐、多氯联苯 (PCB) 和苯酚，特别是双酚 A (BPA)。我们对化学品的选择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 EDC 和 UL 研究受到样本量小、回顾性设计造成的不确定时间性以及 EDC 和 UL 测量结果欠佳的限制。本研究将使用环境生活方式与子宫肌瘤研究 (SELF) 的数据和生物样本，这是一项 NIEHS 前瞻性队列研究，对象为 1,300 名 23-34 岁且基线时（2010-2012 年）无 UL 的非裔美国女性。问卷数据是在基线时收集的，并对受试者进行为期 5 年的跟踪调查。每 20 个月收集一次血液和尿液，并由训练有素的超声检查师进行超声波检查以检测 UL。我们请求支持 EDC 与 UL 发生率相关的实验室和统计分析。我们提出了一种具有成本效益的病例队列研究设计，其中包括 400 个 UL 事件病例和 400 个对照。我们将测量尿液中的邻苯二甲酸酯代谢物、血清 PCB 和尿液 BPA，根据 UL 危险因素描述暴露情况，并确定这些化学物质与 UL 发病率和肿瘤特征的关联。非持久性化学物质（邻苯二甲酸盐、BPA）将在基线、20 个月和 40 个月时进行测量。持久性化学品 (PCB) 将仅在基线处进行测量。 SELF 提供了一个独特的机会来评估常见 EDC 与 UL 风险之间的关联。该项目具有许多克服先前研究局限性的优势：大样本量、前瞻性数据收集、最先进的 EDC 测量、UL 连续超声筛查、重复 EDC 测量分析、评估 EDC 混合物的创新统计方法以及对多种混杂因素的控制。试点数据显示出较大的暴露变异性，为检验所提出的假设提供了极好的能力。这项针对非洲裔美国人（EDC 暴露和 UL 的高危人群）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，并向公众、科学界和政策制定者提供关键数据。