The global burden of breast cancer is on the rise making it the malignancy with the highest incidence among women worldwide. Yet, much of the international variation of breast cancer incidence cannot be explained with known or suspected risk factors. Attention has shifted to earlier time periods of a women's life recognizing the specil susceptibility of the prepubertal mammary gland tissue to environmental influences. The considerable time lag between events prior to or at puberty and diagnosis of breast cancer spanning several decades have made prospective studies difficult to accomplish. Early onset of mammary gland development and high breast density have been associated with an increased risk of breast cancer and can serve as early putative markers of breast cancer risk. A high proportion of radiographically dense area of the breast is one of the strongest known risk factor for breast cancer and may be established at the time of breast development at puberty. We propose to use an existing cohort of about 515 prepubertal Chilean girls born in 2002 to address the relation between putative early markers of breast cancer risk, specifically onset of mammary gland development (Tanner stage 2) and volume of dense breast tissue measured by DXA at Tanner stage 4 and a number of antecedents: endocrine-disrupting chemicals, specifically bisphenol A and phthalates; frequent consumption of high fat dairy products and red meat; blood levels of inflammatory markers, specifically interleukin-6, tumor necrosis factor, and C-reactive protein; global DNA methylation, promoter methylation pattern, and methylation of the ER gene.

Public Health Relevance

Assessing antecedents of the onset of mammary gland development and of breast density at puberty is of paramount importance for understanding determinants of breast cancer susceptibility and pathways through which early breast development and breast density affect breast cancer risk.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA158313-04
Application #
8903737
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Lam, Tram K
Project Start
2012-09-13
Project End
2017-07-31
Budget Start
2015-08-01
Budget End
2017-07-31
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
Binder, Alexandra M; Corvalan, Camila; Calafat, Antonia M et al. (2018) Childhood and adolescent phenol and phthalate exposure and the age of menarche in Latina girls. Environ Health 17:32
Binder, Alexandra M; Stiemsma, Leah T; Keller, Kristen et al. (2018) Inverse association between estrogen receptor-? DNA methylation and breast composition in adolescent Chilean girls. Clin Epigenetics 10:122
Binder, Alexandra M; Corvalan, Camila; Mericq, Ver├│nica et al. (2018) Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls. Epigenetics 13:85-94
Accomando Jr, William P; Michels, Karin B (2018) Multiplexed Reduced Representation Bisulfite Sequencing with Magnetic Bead Fragment Size Selection. Methods Mol Biol 1708:137-159
Binder, Alexandra M; Corvalan, Camila; Pereira, Ana et al. (2018) Prepubertal and Pubertal Endocrine-Disrupting Chemical Exposure and Breast Density among Chilean Adolescents. Cancer Epidemiol Biomarkers Prev 27:1491-1499
Gaskins, Audrey J; Pereira, Ana; Quintiliano, Daiana et al. (2017) Dairy intake in relation to breast and pubertal development in Chilean girls. Am J Clin Nutr 105:1166-1175
Pereira, Ana; Garmendia, Maria Luisa; Uauy, Ricardo et al. (2017) Determinants of volumetric breast density in Chilean premenopausal women. Breast Cancer Res Treat 162:343-352
Gaskins, Audrey J; Corvalán, Camila; Michels, Karin B et al. (2017) Reply to AT Wijayabahu. Am J Clin Nutr 106:707
Carwile, Jenny L; Willett, Walter C; Wang, Molin et al. (2015) Milk Consumption after Age 9 Years Does Not Predict Age at Menarche. J Nutr 145:1900-8
Carwile, J L; Willett, W C; Spiegelman, D et al. (2015) Sugar-sweetened beverage consumption and age at menarche in a prospective study of US girls. Hum Reprod 30:675-83

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