Uterine Leiomyomas

子宫肌瘤

• 批准号: 8553708
• 负责人: DONNA D. BAIRD
• 金额: $ 51.4万
• 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/8553708
• 关键词: Address; African; African American; Age; Alcohol consumption; Attenuated; Benign; Blood Pressure; Blood Specimen Collection; Body mass index; Caliber; Categories; Cervical; Chromosome abnormality; Clinic Visits; Clinical Research; Coitus; Collaborations; Colposcopy; Computer Assisted; Cytogenetics; Data; Data Analyses; Detection; Development; Diagnosis; Dietary Factors; Disease; Enrollment; Environment; Epidemiologic Studies; Estrogens; European; Exhibits; Fertility; Fibroid Tumor; Food; Frequencies; Gene Expression Profile; Genomic Instability; Genomics; Goals; Growth; Health system; Height; Hemorrhage; High Prevalence; Histologic; Hormones; Human Papillomavirus; Hysterectomy; Incidence; Incidence Study; Intraobserver Variability; Lesion; Life; Life Style; Literature; Magnetic Resonance Imaging; Measurement; Measures; Medical; Menarche; Menopause; Menstrual cycle; Michigan; Monitor; Morbidity - disease rate; Mothers; National Institute of Environmental Health Sciences; Online Systems; Pain; Pap smear; Participant; Pattern; Postpartum Period; Postpartum Women; Pregnancy; Pregnancy Histories; Procedures; Progesterone; Prospective Studies; Puberty; Questionnaires; Race; Reporting; Reproductive Tract Infections; Research; Right-On; Risk; Risk Factors; Sampling; Self-Administered; Severities; Skin; Smooth Muscle Tumor; Specimen; Spontaneous abortion; Swab; Symptoms; Telephone Interviews; Testing; Time; Tissues; Transforming Growth Factors; Tumor Tissue; Ultrasonography; United States; Urine; Uterine Fibroids; Vagina; Vitamin D; Vitamin D Deficiency; Weight; Woman; aged; base; cost; design; diaries; early onset; protective effect; tumor; tumor growth

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 four studies. The first, the NIEHS Uterine Fibroid Study, is a large epidemiologic study of black and white women, aged 35-49, in which the randomly selected participants were screened for fibroids with ultrasound. The second study (Fibroid Growth Study, Shyamal Peddada, PI) is a clinical study of fibroids designed to describe fibroid growth. The third study, Postpartum Uterine Regression, monitored fibroid change with pregnancy and postpartum uterine regression. The fourth study, a prospective study of fibroid incidence and growth. All these studies contributed to our research this year. We continue to analyze data from the NIEHS Uterine Fibroid Study. We found that women low vitamin D status is associated with higher prevalence of fibroids in both black and white women. Dietary factors are currently being investigated. We are also analyzing data on the relationship between fibroid size and pain during sexual intercourse as well as fibroid burden and subsequent treatment needs. For the Fibroid Growth Study, stored tumor specimens from the Fibroid Growth Study were examined for genomic loss (and gain) of heterozygosity. We found that small gains were quite common, but major deletions were rare, indicating that tumors do not generally exhibit major genomic instability. Tumor tissue was also analyzed by micro-array to compare gene expression patterns by age and race categories to followup our finding about growth. For the Postpartum Uterine Regression Study, we found that the shrinkage of fibroids associated with pregnancy is attenuated for miscarriages. In addition, black women do not exhibit as much pregnancy-related tumor shrinkage as white women, and postpartum progesterone use appears to inhibit pregnancy-related tumor shrinkage. We began enrolment in a prospective study of fibroids in November, 2010. Our goal is to enroll 1600 African American women 23-34. We have enrolled 1417 to date. The Study of Environment, Lifestyle & Fibroids (SELF) is based in Detroit, Michigan with collaboration from Henry Ford Health Systems. Participants are screened for fibroids with ultrasound at enrollment (detection limit of lesion = 0.5 cm diameter). There will be three subsequent clinic visits at approximately 20-month intervals to monitor fibroids by ultrasound examinations in order to identify onset time. Those found to have fibroids at enrollment (newly detected, not previously clinically diagnosed) as well as those who develop fibroids during the study will be followed in the same manner to assess development of additional new fibroids and to measure fibroid growth. We collect risk factor and symptom data at enrollment and then prospectively for five years. The study is designed to collect a broad spectrum of exposure data including recognized risk factors for fibroids (age of menarche, pregnancy history, alcohol use, body mass index) and potential risk factors for which there has been only suggestive data. Three primary hypotheses will be tested. (1) Vitamin D deficiency is a risk factor for fibroids, (2) Reproductive tract infections are risk factors for fibroids, and (3) A higher proportion of African ancestry is associated with increased fibroid risk (African ancestry measured by informative SNPs known to have very different frequencies between Europeans and Africans). Enrollment activities include: orientation to study, pre-enrollment self-administered questionnaire, web-based questionnaire, food-frequency questionnaire, computer-assisted telephone interview, clinic visit with ultrasound. measure of blood pressure, weight, height, skin reflectance, specimen collection (blood, urine, vaginal swabs), menstrual cycle diary to prospectively record at least one menstrual cycle and bleeding pattern, and an early life questionnaire that the participant administers to her mother (if available). We assessed intra-observer variation in fibroid measurements (for the first 96 women with fibroids) in order to help us evaluate the minimal change we will need to observe (from one ultrasound to another) to determine that tumor growth has occurred. We have also begun examining human papillomavirus-related (HPV) data from the first approximately 700 participants, approximately 28% of whom had fibroids (though no prior diagnosis). Prior data from the literature showed a protective effect of abnormal Pap smear. In our sample a prior abnormal Pap smear was non-significantly associated with a reduced risk of fibroids; colposcopy (the procedure used to followup abnormal Pap results when they persist) was more strongly associated; treatment of cervical lesions was even more strongly associated and the inverse association with fibroids was statistically significant. I also collaborate with Kathie Hartmann on the Right From the Start Study, a pregnancy study that screens participants for fibroids with ultrasound early in their pregnancies. Data from that large study showed no evidence of fibroid related decline in fecundability, but do show increased risk of C-section delivery for those with fibroids. We also replicated previous reports that early age of menarche is a risk factor for fibroids, and extended previous findings by showing that there is increased risk regardless of the type or size of fibroid seen. However, the strength of association was elevated for multiple fibroids suggesting that early age of menarche may be a marker for earlier onset disease or for increased severity.

子宫肌瘤（纤维瘤）是美国子宫切除术的主要适应症。尽管与肌瘤相关的发病率和高昂的医疗费用，在美国却很少有关于这种情况的流行病学研究。子宫肌瘤在组织学上可识别为良性平滑肌肿瘤，具有不同数量的相关纤维组织。许多女性患有不止一种子宫肌瘤，但每一种似乎都具有克隆特征。在肿瘤组织中已经发现了几种特定的细胞遗传学变化，但大多数没有表现出染色体异常。这些良性肿瘤具有激素依赖性。它们在青春期后发展，并在更年期后消退。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。 为了满足该领域的研究需求，我们设计了四项研究。第一项是 NIEHS 子宫肌瘤研究，是一项针对 35-49 岁黑人和白人女性的大型流行病学研究，其中随机选择的参与者通过超声波筛查肌瘤。第二项研究（肌瘤生长研究，Shyamal Peddada，PI）是一项肌瘤临床研究，旨在描述肌瘤生长。第三项研究“产后子宫退化”监测了妊娠期间子宫肌瘤的变化和产后子宫退化。第四项研究是肌瘤发病率和生长的前瞻性研究。所有这些研究都对我们今年的研究做出了贡献。 我们继续分析 NIEHS 子宫肌瘤研究的数据。我们发现，女性维生素 D 水平较低与黑人和白人女性肌瘤患病率较高有关。目前正在研究饮食因素。我们还在分析有关肌瘤大小和性交疼痛以及肌瘤负担和后续治疗需求之间关系的数据。 对于肌瘤生长研究，检查了肌瘤生长研究中保存的肿瘤样本的基因组杂合性丢失（和增加）。我们发现小的增益很常见，但主要的缺失很少见，这表明肿瘤通常不会表现出主要的基因组不稳定性。 还通过微阵列分析肿瘤组织，以按年龄和种族类别比较基因表达模式，以跟踪我们关于生长的发现。 在产后子宫退化研究中，我们发现与怀孕相关的肌瘤收缩因流产而减弱。此外，黑人女性与妊娠相关的肿瘤缩小程度不如白人女性，而且产后使用黄体酮似乎可以抑制与妊娠相关的肿瘤缩小。 我们于 2010 年 11 月开始招募一项肌瘤前瞻性研究。我们的目标是招募 1600 名 23-34 岁的非裔美国女性。迄今为止，我们已经注册了 1417 名学生。环境、生活方式和肌瘤研究 (SELF) 总部位于密歇根州底特律，与亨利·福特健康系统公司合作。参与者在入组时通过超声筛查肌瘤（病变检测限 = 0.5 厘米直径）。随后将每隔大约 20 个月进行 3 次临床就诊，通过超声检查监测肌瘤，以确定发病时间。那些在入组时发现患有肌瘤的人（新发现的，以前没有临床诊断过的）以及那些在研究期间出现肌瘤的人将以相同的方式进行跟踪，以评估其他新肌瘤的发展并测量肌瘤的生长。我们在入组时收集风险因素和症状数据，然后前瞻性地收集五年数据。该研究旨在收集广泛的暴露数据，包括已知的肌瘤风险因素（初潮年龄、怀孕史、饮酒、体重指数）以及仅有提示性数据的潜在风险因素。将测试三个主要假设。 (1) 维生素 D 缺乏是肌瘤的危险因素，(2) 生殖道感染是肌瘤的危险因素，(3) 较高比例的非洲血统与肌瘤风险增加相关（非洲血统通过信息丰富的 SNP 进行测量，已知欧洲人和非洲人之间的频率差异很大）。 招生活动包括：学习指导、招生前自填问卷、网络问卷、食物频率问卷、计算机辅助电话访谈、超声就诊。血压、体重、身高、皮肤反射率的测量、样本采集（血液、尿液、阴道拭子）、前瞻性记录至少一个月经周期和出血模式的月经周期日记，以及参与者向其母亲进行的早期生活调查问卷（如果有）。 我们评估了观察者内部肌瘤测量值的变化（针对前 96 名患有肌瘤的女性），以帮助我们评估我们需要观察的最小变化（从一个超声到另一个超声）以确定肿瘤生长已经发生。 我们还开始检查首批约 700 名参与者的人乳头瘤病毒相关 (HPV) 数据，其中约 28% 患有肌瘤（尽管之前没有诊断）。 先前的文献数据显示异常子宫颈抹片检查具有保护作用。 在我们的样本中，先前异常的子宫颈抹片检查与肌瘤风险降低没有显着相关性。阴道镜检查（当巴氏涂片检查结果持续存在异常时，用于对其进行随访的程序）的相关性更强；宫颈病变的治疗与子宫肌瘤的相关性更强，并且与子宫肌瘤的负相关性具有统计学意义。 我还与凯西·哈特曼 (Kathie Hartmann) 合作开展“从一开始就正确的研究”(Right From the Start Study)，这是一项妊娠研究，在参与者怀孕早期通过超声波筛查肌瘤。 这项大型研究的数据显示，没有证据表明子宫肌瘤与生育能力下降有关，但确实表明子宫肌瘤患者剖腹产的风险增加。 我们还重复了之前的报告，即月经初潮过早是肌瘤的危险因素，并扩展了之前的发现，表明无论肌瘤的类型或大小如何，风险都会增加。 然而，多发性肌瘤的关联强度升高，表明初潮年龄早可能是疾病早发或严重程度增加的标志。