ENVIRONMENTAL AND GENETIC DETERMINANTS OF PUBERTY

青春期的环境和遗传决定因素

• 批准号: 7718125
• 负责人: Mary S Wolff
• 金额: $ 7.48万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718125
• 关键词: 8 year old; Age; Age at Menarche; Biological Markers; Breast; Breast Cancer Risk Factor; Childhood; Clinic; Communities; Computer Retrieval of Information on Scientific Projects Database; Development; Endocrine Disruptors; Endocrine system; Enrollment; Environmental Exposure; Estrogens; Ethnic group; Etiology; Funding; Genetic Determinism; Genetic Polymorphism; Genetic Predisposition to Disease; Grant; Hazard Models; Hormonal; Hormones; Institution; Knowledge; Latina; Life Style; Menarche; New York City; Obesity; Oxidative Stress; Predisposition; Premenopause; Prevention; Puberty; Relative Risks; Research; Research Personnel; Resources; Risk Factors; Societies; Source; Staging; Testing; Time; Today; United States National Institutes of Health; cancer risk; cohort; experience; girls; improved; malignant breast neoplasm; social; stressor

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们建议研究与青春期发育相关的激素活性环境暴露和内源性激素决定因素。 纽约市东哈莱姆区的社区儿科诊所将招募一批 6 岁、7 岁和 8 岁的黑人和拉丁裔女孩。 这两个种族的乳腺癌风险不同，而且乳房发育的年龄也不同。 他们将被跟踪约 5 年，以确定乳房发育每个阶段的年龄、初潮年龄和节奏（定义为从第一次发育中断到初潮的持续时间）。 我们假设环境暴露，包括所谓的内分泌干扰物（或 ED），将导致早期乳房发育的发生和进展，但这种关联在雌激素形成遗传易感性较低和较高、氧化易感性较低的女孩中会有所不同。压力以及高肥胖与低肥胖。 为了检验这一假设，我们将研究环境暴露与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。 将使用雌激素特异性基因多态性、社会压力源和环境暴露（包括 ED 生物标志物）来表征激素和氧化环境。 ED 被选为当今社会最普遍的、也可能影响激素功能的、以及可靠的生物标志物。 在青春期之前和期间，这些危险因素可能会与荷尔蒙和氧化环境协同作用，从而扰乱荷尔蒙系统。 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 阶段和初潮的年龄）以及节奏之间的关联。 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能会提高我们对乳腺癌（尤其是绝经前乳腺癌）危险因素的了解。 如果我们能够识别可改变的外源性暴露和生活方式因素，早期预防是可能的。