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.
Over the past century, adolescent girls have been maturing significantly earlier in the United States, with substantial racial/ethnic differences. Early-maturing girls are at risk for a variety of negative health outcomes, including increased risk of breast and other reproductive cancers, though aside from obesity, little is known as to what early life factors influence the timing of pubertal development. The proposed research will allow me to better understand early determinants of accelerated pubertal development in girls and to identify high risk populations, which can inform future effective upstream cancer prevention strategies.
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