Early Life Determinants of Accelerated Pubertal Development in Adolescent Girls

描述（由申请人提供）：Kubo博士的长期职业目标是了解与肥胖和代谢失调相关的癌症风险因素的早期决定因素，并确定可以从早期干预策略中受益的高风险亚人群。她的主要研究目的是研究宫内暴露于母体妊娠期糖尿病（GDM）、妊娠期体重过度增加、肥胖和婴儿体重快速增加等因素是否会增加青春期女孩青春期加速发病的风险，青春期加速发病是一个重要的乳腺癌和生殖癌危险因素。她的第二个目的是探索所观察到的种族/民族在青春期时间上的差异的原因。之前没有研究调查过这些关联。这些研究目标将利用Kaiser Permanente Northern California （KPNC）提供的电子健康数据，这是一个覆盖约45万女孩的大型综合健康计划。提出了两种具体方法：1。在一项正在进行的青春期女孩性成熟预测因素前瞻性研究中，母亲和女儿的电子健康数据的联系（U01 ES/CA019435）（研究1）；, 2。利用KPNC内的电子数据库建立了一个由20,000对多民族母女组成的新队列（研究2）。研究1将利用CYGNET研究（PI: Lawrence H. Kushi，理学博士）的数据，该研究自2005年以来每年跟踪444名女孩，提供有关青春期发育和人体测量的广泛信息。KPNC GDM和妊娠糖耐量登记处（主任：Assiamira Ferrara， MD, PhD）将与CYGNET数据连接以完成研究1。此外，书记官处将用于建立一个新的母女配对队列。这将使Kubo博士获得建立和跟踪基于KPNC电子病历数据的队列的经验和技能，并探索青春期发病的种族/民族差异。最近在KPNC实施了常规儿科就诊Tanner阶段（一种已建立的评估青春期发育的五阶段分类方案）的电子文档，这种对大量不同儿科人群的可用性使本研究具有独特性和创新性。候选人的研究目标将辅以正式的，有指导的培训，通过课程和量身定制的儿科内分泌学，代际遗传代谢失调，高级生物统计学，癌症预防和健康差异，以及负责任的研究行为。KPNC的研究部是拟议培训的理想环境，因为它提供独特而广泛的电子数据库，可以访问来自大型，多民族成员和国际公认的多学科专家的数据。计划中的科学培训和指导将建立在候选人之前在营养学和癌症流行病学方面的培训基础上，并为她实现目标提供独特的位置。拟议的研究将为建立一个新的队列提供关键技能，为Kubo博士提供一个平台，以开发成功的R01研究，进一步阐明青春期发病和其他癌症风险因素的早期生活决定因素。

DESCRIPTION (provided by applicant): Dr. Kubo's long-term career goal is to understand early-life determinants of cancer risk factors that relate to obesity and metabolic dysregulation, and to identify high-risk sub-populations that can benefit from early intervention strategies. Her primary research aim is to examine whether factors such as intrauterine exposure to maternal gestational diabetes (GDM), excessive gestational weight gain, obesity, and rapid infant weight gain increase the risk of accelerated pubertal onset in adolescent girls, an important breast and reproductive cancer risk factor. Her secondary aim is to explore the causes of the observed racial/ethnic differences in timing of puberty. No previous studies have examined these associations. These research goals will take advantage of electronic health data that are available in Kaiser Permanente Northern California (KPNC), a large integrated health plan that covers about 450,000 girls. Two specific approaches are proposed: 1. Linkage of mothers' and daughters' electronic health data in an on-going prospective study of predictors of sexual maturation in adolescent girls (U01 ES/CA019435) (Study 1); and, 2. Establishment of a new cohort of 20,000 multiethnic mother-daughter pairs using the electronic databases within KPNC (Study 2). Study 1 will utilize data from the CYGNET study (PI: Lawrence H. Kushi, ScD), which has been following 444 girls annually since 2005 with extensive information on pubertal development and anthropometric measures. The KPNC GDM and Pregnancy Glucose Tolerance Registry (Director: Assiamira Ferrara, MD, PhD) will be linked to the CYGNET data to accomplish study 1. In addition, the Registry will be used to establish a new cohort of mother-daughter pairs. This will allow Dr. Kubo gain experience and skills in establishing and follow a cohort based on KPNC electronic medical record data, and to explore racial/ethnic differences in pubertal onset. Electronic documentation of Tanner stage (an established five-stage classification scheme to assess pubertal development) from routine pediatric visits has recently been implemented at KPNC, and this availability on a large and diverse pediatric population makes this study unique and innovative. The candidate's research goals will be complemented with formal, mentored training through coursework and tailored tutorials in pediatric endocrinology, intergenerational transmission of metabolic dysregulation, advanced biostatistics, cancer prevention and health disparities, and responsible conduct of research. KPNC's Division of Research is an ideal environment for the proposed training because it provides unique and extensive electronic databases, access to data from a large, multiethnic membership, and internationally-recognized multidisciplinary experts. The planned scientific training and mentorship will build on the candidate's previous training in nutrition and cancer epidemiology, and uniquely position her to attain her goals. The proposed studies will provide crucial skills in establishing a new cohort, providing a platform for Dr. Kubo to develop successful R01 research to further elucidate early life determinants of pubertal onset and other cancer risk factors.