ENVIRONMENTAL AND GENETIC DETERMINANTS OF PUBERTY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们建议研究激素活性环境暴露和内源性激素决定因素与青春期发育的关系。一组6岁、7岁和8岁的黑人和拉丁裔女孩将在纽约市东哈莱姆的社区儿科诊所注册。这两个民族患乳腺癌的风险不同，而且他们的乳房发育年龄也不同。随访约5年，以确定乳房发育各阶段的年龄、月经初潮年龄和节律（定义为从第一次早餐发育到月经初潮的时间）。我们假设，环境暴露，包括所谓的内分泌干扰物（ed），将有助于早期乳房发育的发生和进展，但这种关联在雌激素形成的遗传易感性较低与较高、氧化应激易感性和高与低肥胖的女孩之间有所不同。为了验证这一假设，环境暴露与青春期里程碑之间的关系将被研究，考虑到激素决定因素、氧化应激和肥胖。激素和氧化环境将通过雌激素特异性遗传多态性、社会压力源和环境暴露（包括ED生物标志物）来表征。ed被选为当今社会中最普遍的，那些可能也影响激素功能的，以及那些可靠的生物标志物。在青春期之前和期间，这些危险因素可能会通过与激素和氧化环境协同作用而扰乱激素系统。风险模型将用于估计风险因素与早熟（乳房发育的青春期B2、B3、B4、B4和初潮年龄）以及速度之间的关系。对联合创始人的相对风险估计将进行调整。更好地了解乳房发育的病因和时间可以提高我们对乳腺癌危险因素的认识，特别是绝经前乳腺癌。如果我们能够确定外源性暴露和生活方式因素是可以改变的，那么早期预防是可能的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose to investigate hormonally active environmental exposures and endogenous hormone determinants in relation to pubertal development. A cohort of 6, 7, and 8-year old Black and Latina girls will be enrolled at community pediatric clinics in East Harlem, New York City. These two ethnic groups experience disparate breast cancer risks, and they undergo breast development at different ages. They will be followed for ~5 years to ascertain age at each stage of breast development, age at menarche, and tempo, defined as the duration from first breakst development until menarche. We hypothesize that environmental exposures, including so-called endocrine disruptors (or EDs) will contribute to the onset and progression of early breast development, but that this association will differ among girls with lower vs. higher genetic susceptibility for estrogen formation, susceptibility to oxidative stress and high vs. low obesity. To test this hypothesis, relationships between environmental exposures and pubertal milestones will be examined, taking into consideration hormonal determinants, oxidative stress, and obesity. The hormonal and oxidative milieu will be characterized using estrogen-specific genetic polymorphisms, social stressors, and environmental exposures, including ED biomarkers. EDs have been selected as those that are most prevalent in society today, those that are likely also to influence hormone function, and those that are reliable biomarkers. Before and during puberty, these risk factors may perturb the hormonal system by acting in concert with the hormonal and oxidative milieu. Hazards models will be used to estimate the association between risk factors and early maturation (ages at pubertal stages B2, B3, B4, B4 of breast development and at menarche) as well as with tempo. Estimates of relative risk will be adjusted for cofounders. Better understanding of the etiology and timing of breast development may improve our knowledge about risk factors for breast cancer, especially premenopausal breast cancer. Early prevention may be possible if we can identify exogenous exposures and lifestyle factors that are modifiable.