Uterine Leiomyomas

子宫肌瘤

• 批准号: 8929726
• 负责人: DONNA D. BAIRD
• 金额: $ 100.46万
• 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/8929726
• 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; Depo Provera; Detection; Development; Diagnosis; Dietary Factors; Disease; Enrollment; Environment; Epidemiologic Studies; Estrogens; European; Exhibits; Extracellular Matrix; 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; Infant; Infection; Intraobserver Variability; Keloid; 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; Visit; Vitamin D; Vitamin D Deficiency; Weight; Woman; aged; base; cost; design; diaries; early onset; feeding; follow-up; protective effect; response; soy; 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 low vitamin D status is associated with higher prevalence of fibroids in both black and white women. Dietary factors are currently being investigated. We have also analyzed 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. We completed enrolment of nearly 1700 African American women 23-34 during this fiscal year. 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 collected 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). We have completed approximately half of the ultrasound examinations for the first of the three follow-up study visits. Enrollment activities included: 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 examined human papillomavirus-related (HPV) data from the first approximately 1200 participants, approximately 25% 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 and colposcopy (the procedure used to followup abnormal Pap results when they persist) were non-significantly associated with a reduced risk of fibroids. For women who were treated for cervical lesions (indicative of the most persistent HPV infections) there was a significant inverse association with fibroids. In an additional analysis of the first 1200 SELF participants, we found that keloids, which had been hypothesized to be associated with fibroids due to their similar extracellular matrix disarray, were not more prevalent in women women with fibroids. We have nearly completed the first 20-month follow-up (response rate so far of 86%). The second follow-up has begun. Twenty-two percent of the participants had fibroids at enrollment. The enrollment data are currently being examine for associations of the following exposures with prevalent fibroids: being fed soy formula as an infant, Depo Provera use, vitamin D (25(OH)D. 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 did 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，我们设计了四项研究。第一项NIEHS子宫肌瘤研究是一项针对黑人和白人妇女的大型流行病学研究，年龄在35-49岁，其中对随机选择的参与者进行了超声检查的肌瘤。第二项研究（肌瘤生长研究，Shyamal Peddada，PI）是一项旨在描述肌瘤生长的肌瘤的临床研究。第三项研究是产后子宫回归，通过怀孕和产后子宫回归监测肌瘤的变化。第四项研究，一项关于肌瘤发生率和生长的前瞻性研究。所有这些研究为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，低维生素D状态与黑人和白人妇女的肌瘤患病率较高有关。目前正在研究饮食因素。我们还分析了性交期间肌瘤大小与疼痛之间的关系的数据，以及肌瘤负担以及随后的治疗需求。 对于肌瘤生长研究，检查了肌瘤生长研究中储存的肿瘤标本的杂合性基因组丧失（和增益）。我们发现，较小的收益非常普遍，但是很少有重大缺失，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，以比较按年龄和种族类别进行基因表达模式，以跟进我们对生长的发现。 对于产后子宫回归研究，我们发现与怀孕有关的肌瘤的收缩因流产而衰减。此外，黑人妇女的肿瘤收缩不如白人妇女表现出那么多，产后孕激素的使用似乎会抑制与妊娠相关的肿瘤收缩。 我们于2010年11月开始入学一项对肌瘤的前瞻性研究。在这个财政年度，我们完成了近1700名非裔美国妇女的入学率。对环境，生活方式和肌瘤（自我）的研究由亨利·福特卫生系统的合作，位于密歇根州底特律。参与者在入学时进行超声检查（病变的检测极限= 0.5 cm）。随后的诊所将在大约20个月的时间间隔内进行三次诊所就诊，以通过超声检查监测肌瘤，以识别发作时间。那些发现在入学率（新检测到的，未经临床诊断的新发现）以及在研究中发展肌瘤的人将以相同的方式遵循，以评估其他新的新肌瘤的发展并测量肌瘤生长。我们在入学时收集了危险因素和症状数据，然后前瞻性五年。该研究旨在收集广泛的暴露数据，包括肌瘤的公认风险因素（初潮，怀孕史，饮酒，体重指数）和仅具有暗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缺乏症是肌瘤的危险因素，（2）生殖道感染是肌瘤的危险因素，（3）（3）非洲血统的较高比例与肌瘤风险增加有关（非洲血统通过欧洲人和非洲人之间的频率非常不同的频率与非洲祖先衡量的相关性）。 在三个后续研究访问中的第一次，我们已经完成了大约一半的超声检查。 入学活动包括：学习介绍，注册前自我管理问卷，基于Web的问卷，食品频率问卷，计算机辅助电话采访，超声检查的诊所访问。血压，体重，身高，皮肤反射率，标本收集（尿液，阴道拭子），月经周期日记的度量，以预期记录至少一个月经周期和出血模式，以及参与者向母亲管理的早期生活调查表（如果有的话）。 我们评估了肌瘤测量（对于前96名具有肌瘤女性）的观察者内变异，以帮助我们评估我们需要观察（从一个超声到另一个超声），以确定发生了肿瘤生长。 我们还研究了大约1200名参与者的人乳头瘤病毒相关（HPV）数据，其中约25％患有肌瘤（尽管没有事先诊断）。 文献中的先前数据显示出异常子宫颈抹片检查的保护作用。 在我们的样品中，先前的异常子宫颈抹片检查和阴道镜（用于持续存在时用于跟进异常子宫颈抹片结果的程序）与肌瘤风险降低无关。 对于接受宫颈病变治疗的妇女（表明最持续的HPV感染）与肌瘤有显着的反相关性。 在对前1200名自我参与者的附加分析中，我们发现，由于其类似的细胞外基质混乱而导致其相似的乳突与肌瘤相关，但在患有辅助女性的女性中并不是更普遍的。 我们几乎完成了第一个20个月的随访（迄今为止的回应率为86％）。 第二次后续行动已经开始。 22％的参与者患有肌瘤。 目前，正在研究注册数据，以了解以下暴露与普遍的肌瘤的关联：被喂食大豆配方作为婴儿，使用Depo Provera，维生素D（25（OH）d）。 我还与凯西·哈特曼（Kathie Hartmann）合作，从开始研究开始，这是一项妊娠研究，该研究在怀孕初期对肌瘤的参与者进行了超声检查。 这项大型研究的数据没有表明肌瘤相关的屈光度下降的证据，但确实显示出患有肌瘤患者的剖腹产风险增加。 我们还复制了先前的报道，即初潮的幼年是肌瘤的危险因素，并通过表明风险增加而不管看到的肌瘤的类型或大小增加了先前的发现。 然而，多种肌瘤的关联强度升高，表明初潮的幼年可能是早期发作疾病或严重程度增加的标志。