Environmental risk factors for uterine fibroids: a prospective ultrasound study

子宫肌瘤的环境危险因素：一项前瞻性超声研究

• 批准号: 9361988
• 负责人: LAUREN A WISE
• 金额: $ 64.6万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9361988
• 关键词: 25-hydroxyvitamin D; Affect; African American; Age; Animal Model; Area; Benign; Biological; Blood; Cadmium; Cells; Characteristics; Chemicals; Clinic Visits; Cobalt; Collection; Common Neoplasm; Data; Data Collection; Diagnosis; Endocrine system; Enrollment; Environment; Environmental Risk Factor; Estrogens; Etiology; Exposure to; Fibroid Tumor; Follow-Up Studies; Funding; Genotype; Gonadal Steroid Hormones; Grant; Growth; Growth and Development function; Gynecologic; Gynecology; Health Care Costs; Health Policy; Health system; Heavy Metals; Hemorrhage; High Prevalence; Hormones; Human; Hysterectomy; Incidence; Infertility; Interview; Lead; Life Style; Location; Long-Term Effects; Longitudinal Studies; Maps; Measurement; Measures; Mercury; Metal exposure; Metals; Methods; Morbidity - disease rate; National Institute of Environmental Health Sciences; Natural History; Operative Surgical Procedures; Participant; Pathogenesis; Pelvic Pain; Persons; Population; Prevalence; Progesterone; Prospective cohort study; Public Health; Risk; Role; Science; Serum; Sex Behavior; Smoking; Source; Statistical Methods; Time; Toxic Environmental Substances; Transvaginal Ultrasound; Ultrasonography; United States; Urine; Uterine Fibroids; Uterine Neoplasms; Visit; Vitamin D; Vitamin D Deficiency; Vitamin D3 Receptor; Whole Blood; Woman; Work; aged; animal data; cigarette smoking; clinical care; cohort; cost; design; follow-up; hormone metabolism; lifetime risk; low socioeconomic status; novel; prospective; receptor binding; reproductive; toxicant; tumor

Uterine leiomyomata (UL), or fibroids, are the most common neoplasms of the uterus and are a major source of gynecologic morbidity. In the United States (U.S.), the lifetime risk of symptomatic UL is approximately 25- 30%. UL are the leading indication for hysterectomy, and UL-related costs exceed $34.4 billion annually. Black women are disproportionately affected by UL, with a 3-fold greater risk of diagnosis, earlier age at diagnosis and surgery, and more symptomatic tumors on average than white women. Despite the large public health burden of UL, little is known about its natural history or pathogenesis. Animal data and cross-sectional human studies have provided compelling preliminary evidence of a role for vitamin D in UL development and growth. Exposure to heavy metals such as lead, mercury, and cadmium is widespread, with reproductive-aged women, African Americans, and those of lower socioeconomic status having higher exposure levels than other groups. Funded by the National Institute of Environmental Health Sciences (NIEHS), the Study of Environment, Lifestyle and Fibroids (SELF) is a multi-year prospective cohort study of UL determinants in black women from the Detroit area. In 2011-2012, SELF enrolled 1,696 black women aged 23-34 years who had never been diagnosed with UL. At baseline and every 20 months for a total of 5 years (4 total clinic visits), SELF participants complete interviews, have blood collected for biological measurements, and undergo transvaginal ultrasounds for precise identification and mapping of UL at each visit facilitating accurate determination of UL development and growth (cohort retention >85%). The final planned clinic visits are underway. In this application, we propose to extend follow-up of SELF for an additional five years. One more clinic visit with transvaginal ultrasound, biospecimen collection and detailed exposure assessments via interview will be conducted to achieve the following specific aims: 1) Describe the natural history of UL initiation and growth; calculate age-specific UL incidence; and evaluate changes in tumor characteristics (size, number, and location) over a 10-year period; 2) Assess whether vitamin D status influences UL incidence and growth over a 10-year period; and 3) Evaluate the influence of selected environmental toxicants on UL incidence and growth. Specifically, we will examine the influence of active and passive cigarette smoking on UL incidence and growth; assess exposure to a panel of 13 metals and metalloids (and their mixtures) measured in whole blood and UL incidence and growth over a 10-year period; and determine whether vitamin D status modifies the associations between environmental toxicants and UL incidence. With its prospective design, population of young black women, serial ultrasounds, repeated collection of data on exposures and covariates, and careful analysis of chemical mixtures, SELF is ideal for identifying environmental risk factors for UL. Using methods that overcome the limitations of prior studies, this will be the most definitive study of modifiable environmental risk factors of UL and is likely to have high impact on science, clinical care, and public health policy.

子宫平滑肌（UL）或肌瘤是子宫最常见的肿瘤，是主要来源 妇科发病率。在美国（美国），有症状性UL的终生风险约为25-- 30％。 UL是子宫切除术的主要指标，与UL相关的成本每年超过344亿美元。黑色的 妇女受UL的影响不成比例，诊断风险更高3倍，诊断年龄更早 和手术，平均比白人女性更多。尽管公共卫生庞大 UL的负担对其自然病史或发病机理知之甚少。动物数据和横断面人类 研究为维生素D在UL发育和生长中的作用提供了令人信服的初步证据。 铅，汞和镉等重金属的暴露是普遍的，生殖年龄的妇女， 非洲裔美国人，社会经济地位较低的人的暴露水平高于其他群体。 由国家环境健康科学研究所（NIEHS）资助，环境研究 生活方式和肌瘤（自我）是一项多年的前瞻性队列研究，对黑人女性的UL决定因素 底特律地区。在2011 - 2012年，自学1,696名23-34岁的黑人妇女从未去过 被诊断为UL。在基线和每20个月的总计5年（4次诊所访问）中，自我 参与者完成访谈，收集血液进行生物学测量，并进行经阴道 超声波可在每次访问时进行精确识别和映射UL，从而有助于准确确定UL 发展与增长（队列保留> 85％）。最终计划的诊所就诊正在进行中。在这个 应用程序，我们建议将自我跟进延长五年。另外一次诊所访问 经阴道超声，生物循环收集和通过访谈的详细暴露评估将是 实现以下特定目的：1）描述UL启动和增长的自然历史； 计算特定年龄的UL发生率；并评估肿瘤特征的变化（大小，数量和 位置）在10年内； 2）评估维生素D状态是否影响U UL的发生率和增长 10年期； 3）评估选定的环境有毒物质对UL发生率和生长的影响。 具体而言，我们将研究活跃和被动吸烟对UL发生率和的影响 生长;评估在全血中测量的13种金属和金属（及其混合物）面板的暴露 在10年期间的发病率和增长；并确定维生素D状态是否修改 环境有毒物质与UL发生率之间的关联。具有前瞻性设计，人口 年轻的黑人妇女，串行超声波，一再收集有关暴露和协变量的数据以及仔细的 化学混合物的分析，自我是确定UL环境风险因素的理想选择。使用方法 这克服了先前研究的局限性，这将是可修改环境的最明确的研究 UL的危险因素，可能会对科学，临床护理和公共卫生政策产生很大影响。