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）是美国子宫切除术的主要指标。尽管与肌瘤相关的发病率和高昂的医疗费用，但在美国，这种情况几乎没有流行病学研究。子宫平滑肌瘤在组织学上可识别为良性平滑肌肿瘤，并具有不同量相关的纤维组织。许多女性具有多个子宫平滑肌瘤，但每个女性似乎都在克隆上截然不同。在肿瘤组织中已经发现了几种特定的细胞遗传学变化，但大多数没有染色体异常。这些良性肿瘤依赖于激素。他们在青春期后发展并在更年期后退缩。雌激素和孕激素都被认为是重要的兴奋剂，或者至少是肿瘤生长的允许因素。 为了满足该领域的研究需求，我们设计了三项研究。第一个是一项大型流行病学研究，即Nieh子宫肌瘤研究，设计为1）估计黑人和白人女性平滑肌瘤的特定年龄特异性累积发生率，35-49岁，35-49，2）疾病的危险因素，3）鉴定肿瘤中的肌脉冲因素与肌分型的相关因素，并在肌分型中匹配的肌分流率，并在肌分流中匹配，并在肌分型中匹配的时间，并在肌分流中匹配。症状包括骨盆疼痛和子宫出血。第二项研究（Barbara Davis，PI）是旨在描述肌瘤生长的肌瘤的临床研究，并比较了生长与非肿瘤肿瘤的生长中间因素。第三项研究通过怀孕和产后子宫回归监测肌瘤的变化。 我们已经跟随妇女进行原始的累积发病率研究，以监测症状的发展。最后的现场工作将于2005年初完成。 在估计黑人和白人妇女子宫肌瘤的年龄特异性发生率后，我们开始检查子宫肌瘤的危险因素。怀孕是保护性的，尽管不是二十多岁之前发生的怀孕。我们关于病毒感染增加风险的假设不受病毒组织标记的支持。酒精似乎增加了风险。在两种情况下，我们从肌瘤的动物模型中复制了发现。我们发现肌瘤的位置在宿害和非偶然的女性中有所不同（9），并且对DES的产前暴露与肌瘤的发育增加有关。 LH的增加与肿瘤患病率的增加有关，从而对患有肌瘤女性的激素替代疗法的安全产生了进一步的怀疑。 使用超声筛查的数据，我们发现患有肌瘤的女性，尤其是大肌瘤的女性更大的子宫出血更大，但是粘膜粘膜纤维（邻近子宫内膜的肌瘤）并不比壁内（肌肉层中的肌瘤）更有问题。此外，知道自己患有肌瘤的女性似乎并没有过多地报告症状。 我们已经在该研究的血浆样品中测量了IGF-I和IGF-ibp3，并将检查这些生物学标记和肌瘤的发生。 NIEHS子宫肌瘤研究的组织样品的摘要组织学测量正在继续。 我们已经在产后子宫回归研究中招募了大约100名女性。 肌瘤生长研究正在继续。现场工作定于2004年9月30日结束。已经开发了基于MRI扫描的肌瘤生长的方法，我们正在系统地评估手术患者固定组织中增殖，血管和胶原蛋白的标志。微阵列分析已经完成，每月问卷数据已用于发展疼痛和出血量表。