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

基本信息

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
项目类别：
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&apos 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

项目摘要

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，并且每年数十亿美元的美国非裔美国人的 UL 发病率是 UL 发病率的 2-3 倍。白人和更严重的疾病与 UL 的病因有关，因为内分泌干扰物 (EDC) 可以改变 UL 的功能。激素，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)。我们选择化学品的依据是它们在人类和体内的高暴露率。体外、动物和人类数据记录了它们对生殖激素和可能影响 UL 风险的过程的影响，现有的 EDC 和 UL 研究受到样本量小、时间不确定的限制。本研究将使用环境生活方式与肌瘤研究 (SELF) 的数据和生物样本，该研究是一项 NIEHS 前瞻性队列研究，对象为 1,300 名 23-34 岁且无 UL 的非裔美国女性。基线（2010-2012 年）收集问卷数据，并对受试者进行为期 5 年的随访，并收集血液和尿液。由训练有素的超声检查人员进行超声检查来检测 UL。我们请求对与 UL 发生率相关的 EDC 进行实验室和统计分析。我们提出了一项具有成本效益的病例队列研究设计，其中包括 400 例 UL 病例和 400 例对照。测量尿邻苯二甲酸酯代谢物、血清 PCB 和尿 BPA，根据 UL 危险因素表征暴露情况，并确定这些化学物质与 UL 发病率和肿瘤特征的关联。非持久性化学品（邻苯二甲酸盐、BPA）将在基线、20 个月时进行测量，而持久性化学品 (PCB) 将仅在基线时进行测量。SELF 提供了评估常见 EDC 与 UL 风险之间关系的独特机会。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 连续超声筛查、重复 EDC 测量分析、用于评估的创新统计方法EDC 混合物和对多种混杂因素的控制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。这项针对非裔美国人（EDC 暴露和 UL 的高风险人群）的研究将提供有关 EDC 暴露和 UL 影响的信息数据。 UL 中广泛存在的污染物，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。