Environmental and Genetic Determinants of Puberty

青春期的环境和遗传决定因素

• 批准号: 8870704
• 负责人: Mary S Wolff
• 金额: $ 4.76万
• 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 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8870704
• 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育相关的激素活性环境暴露和遗传学。在接下来的五年内，他们的黑人和拉丁裔女孩几乎都将迎来初潮并达到成年身高。通过对这两个乳腺癌发病率不同的族群进行持续随访，将有可能完成最初的目标以及研究里程碑，例如少数民族女孩出现得更早且处于乳腺癌中间的峰值身高速度。这些里程碑以及青春期的轨迹将与 BCERP 合作者每年进行评估；终点包括全国 1231 名女孩的乳房阶段、初潮、身高峰值速度、月经周期和身高。 假设环境暴露会影响这些生命阶段的时间和进展。 女孩之间的关联被认为是不同的，多态性编码的雌激素合成、生长和 DNA 调节、外源代谢和肥胖的酶活性较低与较高；与生长和 DNA 甲基化相关的饮食因素不足；以及不同的社会压力。 人们最感兴趣的是所谓的内分泌干扰物或 ED，特别是那些暴露量足够高且足够有效的物质，无论是单独使用还是组合使用，都可以达到生物学相关剂量。 年度访谈和考试将使用将在三个国家站点继续标准化的方法来量化结果、暴露和协变量。 关于暴露源模式以及生物样本中测量的化学物质的大量现有信息将描述广泛的环境暴露。将获得额外的生物样本、环境生物标志物测量和暴露信息，以评估这些暴露在儿童时期的变异性并确定特定的暴露来源。将调查多次暴露的影响。根据初步信息和 ED 生物学，将研究与生长和表观遗传学相关的遗传和饮食因素对暴露效应的修改。 加速失效时间模型将用于估计风险因素与关键结果的年龄以及节奏或这些时间点之间的间隔的关联。风险估计将根据每年收集的 1231 名女孩群体的广泛数据中的混杂因素进行调整。 社区外展和翻译工作将把纽约州东哈莱姆区的黑人和西班牙裔乳腺癌倡导者与我们的研究联系起来，并将研究结果转化为我们的参与家庭、更广泛的社区和全国选区。