Environmental and Genetic Determinants of Puberty

描述（由申请人提供）：在这份申请中，研究者建议继续他们的激素活性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到达月经初潮，达到她们成年时的身高。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，并研究诸如在少数民族女孩中更早出现的峰值身高速度，并且是乳腺癌的中间阶段。每年将与BCERP合作者一起评估这些里程碑以及青春期的轨迹；终点包括1231名全国队列女孩的乳房分期、初潮、最高身高速度、月经周期和达到的身高。

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.