This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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