Environmental risk factors for uterine fibroids: a prospective ultrasound study

子宫肌瘤(UL)，或称肌瘤，是最常见的子宫肿瘤，也是主要来源 妇科疾病的发病率。在美国，有症状的UL的终生风险约为25%- 30%。UL是子宫切除术的主要适应症，与UL相关的费用每年超过344亿美元。黑色 女性受UL的影响不成比例，确诊风险高3倍，确诊年龄更早 和手术，以及平均比白人女性更多的有症状的肿瘤。尽管公共卫生规模很大 UL的负担，对其自然历史和发病机制知之甚少。动物数据和人体剖面图 研究已经提供了令人信服的初步证据，证明维生素D在UL的发育和生长中发挥了作用。 铅、汞和镉等重金属的暴露很普遍，育龄妇女， 非裔美国人，以及那些社会经济地位较低的人比其他群体接触水平更高。 国家环境健康科学研究所(NIEHS)资助的环境研究， 生活方式和肌瘤(SELF)是一项对来自中国的黑人女性UL决定因素的多年前瞻性队列研究 底特律地区。在2011-2012年间，SELF招募了1,696名年龄在23岁至34岁之间的黑人女性，她们从未 被诊断为UL。在基线上，每20个月，共5年(共4次诊所就诊)，自我 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 每次查房时使用超声波精确识别和绘制UL图，便于准确确定UL 发展和增长(队列保留率&85%)。最后计划的诊所就诊正在进行中。在这 申请后，我们建议将SELF的随访时间再延长五年。再来一次诊所 将通过面谈进行经阴道超声、生物脊髓液采集和详细的暴露评估 为实现以下具体目标而进行：1)描述UL发起和发展的自然历史； 计算特定年龄的UL发病率；并评估肿瘤特征(大小、数量和 地点)在10年内；2)评估维生素D状况是否影响UL的发病率和增长 3)评估选定的环境毒物对UL发病率和生长的影响。 具体地说，我们将研究主动和被动吸烟对UL发病率的影响以及 生长；评估在全血中测量的13种金属和类金属(及其混合物)的暴露 和UL在10年内的发病率和增长；并确定维生素D状态是否会改变 环境毒物与UL发病率之间的关系。凭借其前瞻性的设计，人口 年轻的黑人女性，连续的超声波，反复收集关于暴露和协变量的数据，并仔细 对于化学混合物的分析，SELF是识别UL环境风险因素的理想选择。使用方法 克服了以前研究的局限性，这将是对可改变环境的最明确的研究 UL的风险因素，并可能对科学、临床护理和公共卫生政策产生很大影响。

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.