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

基本信息

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
项目类别：
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

项目摘要

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.

子宫平滑肌瘤 (UL) 或肌瘤是最常见的子宫肿瘤，也是子宫肌瘤的主要来源妇科发病率。在美国 (U.S.)，有症状 UL 的终生风险约为 25- 30%。 UL 是子宫切除术的主要适应症，每年 UL 相关费用超过 344 亿美元。黑色的女性受 UL 影响的比例更高，诊断风险高出 3 倍，且诊断年龄较早和手术，并且平均比白人女性有更多有症状的肿瘤。尽管公共卫生领域规模巨大 UL 的负担，但对其自然史或发病机制知之甚少。动物数据和人体横断面数据研究提供了令人信服的初步证据，证明维生素 D 在 UL 发育和生长中的作用。育龄妇女普遍接触铅、汞和镉等重金属，非裔美国人和社会经济地位较低的人比其他群体的接触水平更高。由国家环境健康科学研究所 (NIEHS) 资助，环境研究，生活方式与肌瘤 (SELF) 是一项针对黑人女性 UL 决定因素的多年前瞻性队列研究底特律地区。 2011-2012 年，SELF 招募了 1,696 名年龄在 23-34 岁之间且从未参加过诊断为 UL。在基线时和每 20 个月一次，总共 5 年（总共 4 次就诊），SELF 参与者完成访谈，采集血液进行生物测量，并接受经阴道检查每次就诊时使用超声波进行 UL 的精确识别和绘图，有助于准确确定 UL 发育和成长（队列保留>85%）。最终计划的门诊就诊正在进行中。在这个申请后，我们建议将 SELF 的随访再延长五年。再一次到诊所就诊经阴道超声、生物样本采集和通过面谈进行的详细暴露评估将为实现以下具体目标而进行： 1) 描述 UL 起始和生长的自然历史；计算特定年龄的 UL 发病率；并评估肿瘤特征的变化（大小、数量和位置）超过 10 年； 2) 评估维生素 D 状态是否会影响 UL 的发病率和生长 10年期； 3) 评估选定的环境毒物对 UL 发病率和生长的影响。具体来说，我们将研究主动和被动吸烟对 UL 发病率的影响以及生长;评估全血中测量的 13 种金属和类金属（及其混合物）的暴露情况 10 年期间 UL 的发病率和增长情况；并确定维生素 D 状态是否会改变环境毒物与 UL 发病率之间的关联。凭借其前瞻性的设计，人口年轻的黑人女性，连续超声检查，重复收集暴露和协变量的数据，并小心在化学混合物分析中，SELF 是识别 UL 环境风险因素的理想选择。使用方法克服了先前研究的局限性，这将是可改变环境的最权威的研究 UL 的危险因素，可能对科学、临床护理和公共卫生政策产生重大影响。