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：
9302417
负责人：
LAUREN A WISE
金额：
$ 64.33万
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/9302417
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 Estrogens Etiology Exposure to Fibroid Tumor Gonadal Steroid Hormones Gynecologic Gynecology Health Care Costs Health Care Research High Prevalence Hormone Receptor Hormones Human Hysterectomy In Vitro Incidence Individual Infertility Laboratories Laboratory Study Life Style Link Location Measurement Measures Menorrhagia Methodology 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 Prospective cohort study Questionnaires Reproductive Process Research Research Design Research Infrastructure Research Priority Risk Risk Factors Sample Size Sampling Serum Severities Severity of illness Sex Behavior Source Statistical Data Interpretation Symptoms Testing Time Training Ultrasonography United States United States National Institutes of Health Urine Uterine Fibroids Woman Women&apos s Health aged animal data base bisphenol A case control chemical association clinically significant cost cost effective design disorder prevention epidemiology study health care quality high risk population human data innovation parity phthalates pollutant prospective public health relevance racial disparity racial health 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（由适用提供）：子宫平滑肌瘤（UL）在25-30％的生殖妇女中被诊断出，因此考虑到妇科发病率和数十亿美元的美国医疗保健费用。非洲裔美国人的白人事件的2-3倍和疾病严重程度更大。性类固醇激素参与UL的病因。鉴于内分泌干扰化学物质（EDC）可以改变激素的功能，我们建议评估与3种EDC相关的UL风险：邻苯二甲酸酯，多氯联苯双苯基（PCB）和苯酚，特别是双酚A（BPA）。我们选择的化学物质的选择是由于它们在人类中的高暴露率以及在体外，动物和人类数据中的高暴露率，这些数据记录了它们对可能影响UL风险的生殖激素和过程的影响。现有的EDC和UL研究受到样本量较小，由于回顾性设计而导致的时间不确定的限制以及EDC和UL的次优测量。这项研究将使用来自环境生活方式和肌瘤研究（自我）研究的数据和生物测量，对1300名23-34岁的非裔美国妇女的NIEHS前瞻性队列研究（2010-2012）。在基线时收集问卷数据，并遵循了5年的受试者。每20个月，血液和尿液我们将根据UL危险因素测量邻苯二甲酸酯代谢产物，血清PCB和尿BPA的特征，并确定这些化学物质与UL入射和肿瘤特征的关联。在基线，20个月和40个月时，将测量非持久化学物质（邻苯二甲酸盐，BPA）。仅在基线时测量持久化学物质（PCB）。自我提供了一个独特的机会来评估普通EDC与UL风险的关联。该项目具有许多优势，可以克服先前研究的局限性：大型样本量，前瞻性数据收集，最先进的EDC测量，用于UL的串行超声筛选，对重复EDC测量的分析，用于评估EDC混合物的创新统计方法以及多个混合物的控制。飞行员数据显示出较大的暴露变异性，为检验提出的假设提供了出色的能力。这项对非洲裔美国人的研究是一种用于EDC暴露和UL的高风险人群，将提供有关宽度污染物对UL的影响的信息数据，寻求解释UL事件中的种族差异，并向公共，科学界和政策制定者提供关键数据。