Environmental and Genetic Determinants of Puberty

描述(由申请人提供)：在这份申请中，研究人员建议继续他们对荷尔蒙活跃的环境暴露和与青春期发育有关的遗传学的研究。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月经初潮并达到成年身高。通过对这两个乳腺癌发病率不同的民族的持续跟踪，将有可能完成最初的目标以及研究里程碑，例如在少数族裔女孩中出现得更早的峰值身高速度，这是乳腺癌的中间阶段。这些里程碑以及整个青春期的轨迹将与BCERP的合作者一起每年进行评估；终点包括乳房阶段、月经初潮、身高峰值速度、月经周期和在全国1231名女孩队列中达到的身高。 环境暴露被认为有助于这些生命阶段的时间和进程。研究表明，在女孩中，雌激素合成、生长和DNA调节、异物代谢和肥胖；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的多态编码的酶活性较低或较高，其相关性不同。最令人感兴趣的是所谓的内分泌干扰物或ED，特别是那些暴露在足够高和足够有效的环境中，无论是单独接触还是潜在的组合，都能达到生物相关的剂量。 年度面试和考试将使用在三个国家网站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在生物检疫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情况。将获得额外的生物标记物、环境生物标记物测量和暴露信息，以评估这些暴露在儿童时期的可变性，并确定具体的暴露来源。将调查多次曝光的影响。在初步信息和EDS生物学的基础上，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修改。 加速失效时间模型将被用来估计危险因素与关键结局时的年龄以及节奏或这些时间点之间的间隔的关联。对混杂因素的风险估计将从每年收集的1231名女孩队列的广泛数据中进行调整。 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，并将研究结果翻译给我们的参与家庭、更广泛的社区和全国选民。

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.