Uterine Leiomyomas

子宫肌瘤

• 批准号: 7007383
• 负责人: DONNA D. BAIRD
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7007383
• 关键词: age difference; biomarker; cancer risk; clinical research; cytogenetics; disease /disorder etiology; disease /disorder onset; environmental exposure; female; human middle age (35-64); human subject; interview; lactation; leiomyoma; magnetic resonance imaging; neoplasm /cancer epidemiology; neoplasm /cancer genetics; neoplastic growth; obesity; phthalates; pregnancy; smoking; tobacco abuse; ultrasound; uterus neoplasms

Uterine leiomyomas (fibroids) are the leading indication for hysterectomy in the United States. Despite the morbidity and high medical costs associated with fibroids, there has been little epidemiologic study of this condition in the United States. Uterine leiomyomas are histologically identifiable as benign smooth muscle tumors with varying amounts of associated fibrous tissue. Many women have more than one uterine leiomyoma, but each appears to be clonally distinct. Several specific cytogenetic changes have been identified in tumor tissue, but most show no chromosomal abnormalities. These benign tumors are hormone-dependent. They develop after puberty and regress after menopause. Both estrogen and progesterone are considered important stimulants, or at least permissive factors for tumor growth. To address the research needs in this field we have designed three studies. The first is a large epidemiologic study, the NIEHS Uterine Fibroid Study, designed to 1) estimate the age-specific cumulative incidence of leiomyomas in black and white women, aged 35-49, 2) identify risk factors for the condition, 3) compare growth mediating factors in tumor and matching myometrial tissues collected at time of hysterectomy, and 4) to identify factors associated with development of fibroid symptoms including pelvic pain and uterine bleeding. The second study (Barbara Davis, PI) is a clinical study of fibroids designed to describe fibroid growth and compare the growth-mediating factors in growing vs nongrowing tumors. The third study monitors fibroid change with pregnancy and postpartum uterine regression. We have followed the women in the original cumulative incidence study to monitor symptom development. The final field work will be completed in early 2005. After estimating the age-specific incidence of uterine fibroids for black and white women, we began to examine risk factors for uterine fibroids. Pregnancy is protective, though not those that occur before the mid twenties. Our hypothesis that viral infection increases risk was not supported by viral tissue markers. Alcohol appears to increase risk. In two cases we have replicated findings from animal models of fibroids. We find that the location of fibroids is somewhat different for parous and nonpauous women (9), and that prenatal exposure to DES is associated with increased development of fibroids. Increasing LH is associated with increased prevalence of the tumors, raising further doubts about the safety of hormone replacement therapy for women with fibroids. Using the data from ultrasound screening, we find that heavy uterine bleeding is greater for women with fibroids, especially large fibroids, but that submucous fibroids (those that abut the endometrium) are not more problematic than intramural (those within the muscle layer). Furthermore, women who know they have fibroids do not appear to over-report their symptoms. We have measured IGF-I and IGF-IBP3 in plasma samples from the study, and will examine these biological markers and fibroid occurrence. Summary histological measures of the tissue samples from the NIEHS Uterine Fibroid Study are continuing. We have enrolled approximately 100 women in the Postpartum Uterine Regression Study. The Fibroid Growth Study is continuing. Field work is scheduled to end September 30, 2004. Methods for measuring fibroid growth based on the MRI scans have been developed, and we are systematically assessing markers of proliferation, vascularity and collagen in the fixed tissues from surgical patients. Micro-array analyses have been completed and monthly questionnaire data have been used to develop pain and bleeding scales.

子宫平滑肌瘤（肌瘤）是子宫切除术在美国的主要适应症。尽管与肌瘤相关的发病率和高昂的医疗费用，在美国很少有这种情况的流行病学研究。子宫平滑肌瘤在组织学上可被鉴别为良性平滑肌肿瘤，伴有不同数量的相关纤维组织。许多妇女有一个以上的子宫肌瘤，但每个似乎是克隆不同。在肿瘤组织中发现了几种特异性的细胞遗传学改变，但大多数没有显示染色体异常。这些良性肿瘤依赖于肿瘤生长。它们在青春期后发育，在绝经后退化。雌激素和孕激素都被认为是重要的刺激物，或者至少是肿瘤生长的允许因素。 为了满足这一领域的研究需求，我们设计了三项研究。第一项是大型流行病学研究，NIEHS子宫肌瘤研究，旨在1）估计年龄在35-49岁的黑人和白色妇女中平滑肌瘤的年龄特异性累积发病率，2）确定该疾病的风险因素，3）比较子宫切除术时收集的肿瘤和匹配的子宫肌层组织中的生长介导因子，和4）确定与纤维瘤症状包括盆腔疼痛和子宫出血的发展相关的因素。第二项研究（Barbara Davis，PI）是一项肌瘤临床研究，旨在描述肌瘤生长并比较生长与非生长肿瘤中的生长介导因子。第三项研究监测子宫肌瘤的变化与怀孕和产后子宫退化。 我们在最初的累积发病率研究中对妇女进行了随访，以监测症状的发展。最后的实地工作将于2005年初完成。 在估计了黑人和白色妇女子宫肌瘤的年龄特异性发病率后，我们开始研究子宫肌瘤的危险因素。怀孕是有保护作用的，但不是那些发生在20多岁之前的人。我们关于病毒感染增加风险的假设没有得到病毒组织标志物的支持。酒精似乎会增加风险。在两种情况下，我们复制了肌瘤动物模型的发现。我们发现经产妇女和非经产妇女子宫肌瘤的位置有所不同（9），产前暴露于DES与子宫肌瘤的发生增加有关。 LH增加与肿瘤患病率增加有关，进一步怀疑激素替代疗法对子宫肌瘤妇女的安全性。 使用超声筛查的数据，我们发现子宫肌瘤，特别是大肌瘤的女性子宫出血量更大，但粘膜下肌瘤（与子宫内膜相邻的肌瘤）并不比壁内肌瘤（肌肉层内的肌瘤）更有问题。此外，知道自己患有子宫肌瘤的女性似乎不会过度报告其症状。 我们已经测量了来自研究的血浆样本中的IGF-I和IGF-IBP 3，并将检查这些生物标志物和纤维瘤的发生。 NIEHS子宫肌瘤研究的组织样本的组织学测量总结仍在继续。 我们在产后子宫退化研究中招募了大约100名妇女。 子宫肌瘤生长研究仍在继续。实地工作定于2004年9月30日结束。已经开发出基于MRI扫描测量肌瘤生长的方法，我们正在系统地评估手术患者固定组织中的增殖、血管分布和胶原蛋白标记物。微阵列分析已经完成，每月问卷调查数据已被用于开发疼痛和出血量表。