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. Background: Past studies suggest that early menarche, growth velocity, and specific hormonal patterns during breast development may be critical in determining risk of breast cancer later in life. Nutritional factors (i.e., adiposity, physical activity and diet) during childhood and puberty, and inherited genetic factors are suspected to modulate these early-life exposures. However, the biological processes involved remain poorly understood. These factors may explain the remarkable increase in breast cancer incidence observed among US-born Asian women. Objective: We propose to test the relationships of nutrition, genetic factors and hormonal levels with early life events contributing to breast cancer risk in a unique cohort of 349 adolescent girls of Caucasian or Asian ancestry originally recruited for the Female Adolescent Maturation (FAM) Study (USDA NRI grant 99-00700, PI: R. Novotny). These girls were first studied in 1999-2000 at age 9-14 years and, again two years later in 2002-2003, for dietary intake, body size and composition, sexual maturation (Tanner staging), growth and bone density. Data collection will be extended by conducting a third examination and obtaining blood and urine samples for DNA genotyping and hormone analysis at a time when almost all girls will have attained menarche. A cross-sectional sample of 140 additional girls will also be recruited.
Specific Aims :
The aims i nclude the testing of the associations of functional polymorphisms in genes involved in sex hormone metabolism, or coding for growth promoting hormones and related-proteins, with early menarche, early breast development, accelerated growth, higher bone density, and elevated sex and IGF-I hormones, which have all been associated with an elevated risk of developing breast cancer later in life. Another aim will test the associations of adolescent diet, physical activity, abdominal adiposity and pubertal stage with decreased levels of IGFBP-1, and elevated levels of estradiol, IGF-I, leptin, and C-peptide, a marker of insulin secretion. Study Design: Data, blood and urine will be collected on 160 girls, aged 13-18 years, who participated in the FAM study, a cohort study on the nutritional determinants of childhood obesity and bone health. The repeat measures include a 3-day food record, physical activity record, anthropometric measures, calcaneal bone ultrasound, DXA scan for bone density and body composition, and Tanner staging by clinical exam for pubertal maturation. The new measures will include genotype for functional polymorphisms in the genes mentioned above and serum levels of sex steroid hormones, IGF-I hormones, leptin and C-peptide. Another 140 new participants, aged 13-17 years, will be recruited in the same way and provide the same data as the FAM participants to increase the sample size to 300 girls. Relevance: The study would provide critical evidence in support of the causal involvement of specific biological pathways in early maturation and may reveal possible means for the early prevention of breast cancer through lifestyle modification.
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