Environmental and Genetic Determinants of Puberty

青春期的环境和遗传决定因素

• 批准号: 8143397
• 负责人: Mary S Wolff
• 金额: $ 108.39万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8143397
• 关键词: Acceleration; Address; Adolescence; Adult; Advocate; Age; Biological; Biological Markers; Biology; Birth; Body Size; Body fat; Breast; Breast Cancer Risk Factor; Carbon; Characteristics; Chemical Exposure; Chemicals; Childhood; Code; Communities; Community Outreach; DNA; DNA Methylation; Data; Development; Diet; Dietary Factors; Dose; Endocrine Disruptors; Enrollment; Entire hair of pubis; Environment; Environmental Exposure; Epigenetic Process; Estrogens; Ethnic group; Exposure to; Failure; Family; Folate; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Variation; Growth; Height; Hispanics; Incentives; Incidence; Inherited; Intake; Interview; Latina; Life; Link; Measurement; Measures; Mediating; Medical History; Menarche; Metabolism; Methods; Minority; Modeling; Modification; Neighborhoods; Nucleic Acid Regulatory Sequences; Obesity; Outcome; Participant; Pathway interactions; Pattern; Perinatal Exposure; Periodicity; Peroxisome Proliferator-Activated Receptors; Physical activity; Policies; Population Study; Principal Investigator; Production; Puberty; RNA; Regulation; Reporting; Research Personnel; Risk Estimate; Risk Factors; Sampling; Site; Snow; Source; Staging; Steroids; Structure; Thyroid Gland; Time; Translating; Translations; Vitamin D; Xenobiotic Metabolism; base; cohort; design; endocrine disruptor exposure; enzyme activity; experience; follow-up; girls; interest; malignant breast neoplasm; outreach; phthalates; psychosocial; social stress; socioeconomics

DESCRIPTION (provided by applicant): In this application, the investigators propose to continue their study of hormonally active environmental exposures and genetics in relation to pubertal development. Within the next 5 years, their cohort of Black and Latina girls will have virtually all reached menarche and attained their adult height. Through continued follow-up of these two ethnic groups who experience disparate breast cancer incidence rates, it will be possible to complete the original aims as well as study milestones such as peak height velocity that occur much earlier in minority girls and are intermediate to breast cancer. These milestones along with the trajectories through adolescence will be assessed annually with BCERP collaborators; endpoints include breast stages, menarche, peak height velocity, menstrual cyclicity, and attained height in the national cohort of 1231 girls. Environmental exposures are hypothesized to contribute to the timing and progression of these life stages. Association are proposed to differ among girls with polymorphisms coding for lower vs. higher enzyme activity for estrogen synthesis, growth and DNA regulation, xenobiotic metabolism, and obesity; for deficient dietary factors related to growth and DNA methylation; and for differing social stress. Of major interest are the so-called endocrine disrupters or EDs, particularly those with exposures that are high enough and potent enough, both individually and potentially in combination, that achieve a biologically relevant dose. Annual interviews and exams will quantify outcomes, exposures and covariates using methods that will continue to be standardized across three national sites. Extensive existing information on exposure source patterns as well as chemicals measured in biospecimens will describe a broad range of environmental exposures. Additional biospecimens, environmental biomarker measurements, and exposure information will be obtained to assess variability of these exposures over childhood and to identify specific sources of exposure. The impact of multiple exposures will be investigated. Based on preliminary information and the biology of EDs, modification of exposure effects by genetic and dietary factors related to growth and epigenetics will be studied. Accelerated failure time models will be used to estimate the association of risk factors with ages at the critical outcomes as well as with tempos, or intervals between these time points. Risk estimates will be adjusted for confounders from the extensive data collected annually on the cohort of 1231 girls. The Community Outreach and Translation efforts will link established black and Hispanic breast cancer advocates in East Harlem, NY with our study and will translate findings to our participating families, the wider community, and the national constituency.

描述（由申请人提供）：在本申请中，研究人员建议继续研究与青春期发展有关的荷尔蒙活跃环境暴露和遗传学。在接下来的5年内，他们的黑人和拉丁裔女孩队伍几乎全部达到了初潮，并达到了成人身高。通过持续的这两个族裔群体，他们经历了不同的乳腺癌发病率，可以完成原始目标以及研究里程碑，例如峰值高度速度，在少数族裔女孩中发生得很早，并且涉及乳腺癌。这些里程碑以及通过青春期的轨迹以及BCERP合作者每年都会进行评估；终点包括乳房阶段，初潮，峰高速度，月经循环以及在1231名女孩的国家队列中达到的高度。 假设环境暴露有助于这些生活阶段的时间和发展。 提出关联是在编码雌激素合成，生长和DNA调节，异种生物代谢和肥胖症的较低酶活性的多态性和较高酶活性的女孩中的不同。对于与生长和DNA甲基化有关的缺乏饮食因素；以及不同的社会压力。 主要感兴趣的是所谓的内分泌烦恼或ED，尤其是那些具有足够高且有效的曝光的人，无论是单独和潜在的，都可以实现与生物学相关的剂量。 年度访谈和考试将使用将继续在三个国家地点进行标准化的方法来量化结果，暴露和协变量。 有关暴露源模式以及在生物测量中测得的化学物质的广泛现有信息将描述广泛的环境暴露。还将获得其他生物测量，环境生物标志物测量和暴露信息，以评估童年时期这些暴露的变异性并确定特定的暴露源。将研究多次暴露的影响。基于初步信息和ED的生物学，将研究与生长和表观遗传学有关的遗传和饮食因素的暴露效应。 加速故障时间模型将用于估计危险因素与关键结果以及节奏的年龄的关联，或这些时间点之间的间隔。从每年收集的1231名女孩队列中收集的大量数据中，将对混杂因素进行调整的风险估计。 社区外展和翻译工作将与我们的研究联系在纽约州东哈林市建立的黑人和西班牙乳腺癌倡导者，并将发现结果转化为我们参与的家庭，更广阔的社区和国家选区。