ENVIRONMENTAL AND GENETIC DETERMINANTS OF PUBERTY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们建议调查荷尔蒙活跃的环境暴露和内源性激素决定因素与青春期发育的关系。一群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区的社区儿科诊所登记。这两个民族患乳腺癌的风险不同，他们在不同的年龄经历乳房发育。他们将被跟踪大约5年，以确定乳房发育每个阶段的年龄、月经初潮年龄和节奏，节奏的定义是从第一次乳房破裂发育到初潮的持续时间。 我们假设，环境暴露，包括所谓的内分泌干扰物(EDs)，将有助于乳房早期发育的发生和发展，但这种联系在雌激素形成的遗传敏感度较低和较高、氧化应激易感性和肥胖度较高和较低的女孩中有所不同。为了验证这一假设，我们将研究环境暴露和青春期里程碑之间的关系，同时考虑荷尔蒙决定因素、氧化应激和肥胖。荷尔蒙和氧化环境将使用雌激素特有的遗传多态、社会应激源和环境暴露来表征，包括ED生物标志物。EDS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。在青春期之前和青春期期间，这些危险因素可能会与荷尔蒙和氧化环境协同作用，扰乱荷尔蒙系统。风险模型将被用来估计风险因素与早熟(乳房发育的青春期阶段B2、B3、B4、B4以及月经初潮时的年龄)以及节奏之间的关系。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机可能会提高我们对乳腺癌，特别是绝经前乳腺癌的危险因素的了解。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.