Environmental risk factors for uterine fibroids: a prospective ultrasound study(Supplement)

资助家长资助金摘要(R01-ES024749) 25%-30%的育龄妇女被诊断为子宫肌瘤(UL)，导致 每年有相当大的妇科发病率和数十亿美元的美国医疗费用。非洲 美国人的白人发病率是UL的2-3倍，疾病更严重。性激素 激素参与了UL的发病机制。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类激素相关的UL风险 内源性化合物：邻苯二甲酸盐、多氯联苯和酚，特别是双酚A(BPA)。 我们选择化学物质是因为它们在人体内的高暴露流行率和体外试验， 动物和人类数据记录了它们对生殖激素和生殖过程的影响 可能会影响UL风险。现有对EDCS和UL的研究受样本量小的限制， 由于追溯设计和EDC和UL的次优测量而导致的不确定时间性。 这项研究将使用环境生活方式和肌瘤研究中的数据和生物标本 (SELF)，NIEHS对1300名年龄在23-34岁和 基线(2010-2012年)不含UL。在基线和受试者处收集问卷数据 被跟踪了5年。每隔20个月，就会采集血液和尿液，并进行超声波检查 由训练有素的超声技师进行检查以检测UL。我们请求为实验室提供支持 内分泌细胞与UL发病率的统计分析。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例急性UL病例和400例对照。我们会测量尿量 根据UL，邻苯二甲酸盐代谢物、血清多氯联苯和尿双酚A是暴露的特征 危险因素，并确定这些化学物质与UL发病率和肿瘤的相关性 特点。非持久性化学品(邻苯二甲酸盐、双酚A)将在基线时进行测量，20 几个月，还有40个月。持久性化学品(多氯联苯)将仅在基线时进行测量。自性 提供了一个独特的机会来评估常见的EDC与UL风险的关联。这 该项目具有许多优点，克服了以前研究的局限性：样本量大， 前瞻性数据收集、最先进的EDC测量、系列超声筛查 UL，重复EDC测量分析，评估EDC的创新统计方法 混合物，以及对多个混杂物的控制。试点数据显示，暴露的可变性很大， 为检验所提出的假说提供了极好的动力。这项对非裔美国人的研究， EDC暴露和UL的高危人群，将提供有关以下影响的信息数据 UL上普遍存在的污染物，寻求解释UL发病率的种族差异，以及 向公众、科学界和政策制定者提供关键数据。

Abstract of Funded Parent Grant (R01-ES024749) 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.