Environmental and Genetic Determinants of Puberty

描述（由申请人提供）：在本申请中，研究者建议继续研究与青春期发育相关的生殖活性环境暴露和遗传学。在接下来的5年里，他们的黑人和拉丁裔女孩几乎都将达到初潮并达到成年身高。通过对这两个经历不同乳腺癌发病率的种族群体的持续随访，将有可能完成最初的目标以及研究里程碑，例如少数民族女孩发生更早的峰值身高增长速度，并且是乳腺癌的中间阶段。这些里程碑沿着青春期轨迹将由BCERP合作者每年评估一次;终点包括乳房分期、月经初潮、身高峰值速度、月经周期和全国1231名女孩队列中的身高。 环境暴露被假设为有助于这些生命阶段的时间和进展。 协会提出了不同的女孩与多态性编码较低与较高的酶活性的雌激素合成，生长和DNA调节，异源生物质代谢和肥胖症;缺乏饮食因素相关的生长和DNA甲基化;和不同的社会压力。 主要关注的是所谓的内分泌干扰物或ED，特别是那些暴露量足够高和足够强的物质，无论是单独还是潜在的组合，都达到了生物相关剂量。 年度访谈和考试将使用在三个国家地点继续标准化的方法量化结果、暴露和协变量。 关于接触源模式以及在生物样本中测量的化学品的大量现有信息将描述广泛的环境接触。将获得额外的生物样本、环境生物标志物测量结果和接触信息，以评估儿童期这些接触的变化，并确定具体的接触源。将调查多次接触的影响。根据初步信息和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对暴露影响的影响。 加速失效时间模型将用于估计风险因素与关键结局时的年龄以及与节奏或这些时间点之间的间隔的相关性。将根据每年收集的1231名女孩队列的大量数据调整风险估计值的混杂因素。 社区外展和翻译工作将联系建立黑人和西班牙裔乳腺癌倡导者在东哈莱姆，纽约与我们的研究，并将研究结果转化为我们的参与家庭，更广泛的社区，和国家选区。

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.