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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们建议研究与青春期发育有关的激素活跃环境暴露和内源性激素决定因素。 纽约市东哈林的社区儿科诊所将招募6、7和8岁的黑人和Latina Girls组成的队列。 这两个族裔遭受不同的乳腺癌风险，并且在不同年龄段的乳房发育。 在乳房发育的每个阶段，初潮的年龄和节奏定义为从第一次断裂发展到初潮的持续时间。 我们假设环境暴露，包括所谓的内分泌破坏者（或EDS）将有助于早期乳房发育的发作和发展，但是这种关联在雌激素形成，较高的遗传易感性，氧化应激的易感性较低的女孩中会有所不同，对氧化应激的敏感性和高肥胖症。 为了检验这一假设，将研究荷尔蒙决定因素，氧化应激和肥胖症，将检查环境暴露与青春期里程碑之间的关系。 激素和氧化环境将使用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人，那些也可能影响激素功能的人以及那些是可靠的生物标志物的人。 在青春期之前和期间，这些危险因素可能通过与荷尔蒙和氧化环境一致作用来扰动激素系统。 危害模型将用于估计危险因素与早期成熟之间的关联（青春期阶段B2，B3，B4，B4，B4，B4的乳房发育和初潮）以及与Tempo。 联合创始人将调整相对风险的估计。 更好地了解乳房发育的病因和时机可以提高我们对乳腺癌危险因素的了解，尤其是绝经前乳腺癌。 如果我们可以识别可修改的外源性暴露和生活方式因素，则可能是可能的。