The overall objective of the two proposed Center Collaborative Research Projects is to fill specific gaps in our knowledge of the impact of in utero, early postnatal and pubertal environmental exposures on mammary gland development at the cellular, molecular, organ and population levels and their influence on future breast cancer risk. This will be accomplished through 1) an epidemiological study to identify early exposures that can influence breast cancer risk through their effects on breast development in utero through puberty. This study takes advantage of a unique opportunity to follow-up a multiethnic cohort of 500 girls ages 4-11 for whom we have extensive in utero exposures and birth characteristics information and the opportunity to prospectively collect their childhood exposures that influence their hormonal milieu (estrogens, antiestrogens) and growth (diet, exercise, stress, insulin biomarkers), identify relevant genetic polymorphisms and relate them to the timing of pubertal development. 2) The second collaborative research project will use the mouse mammary gland model to determine the molecular mechanisms of mammary gland pubertal development and maturation through in vivo and in vitro studies on the mechanism of progesterone action focusing on the roles of PRA and PRB isoforms. In parallel with the epidemiological studies, the effects of in utero, lactational and postnatal exposures to environmental estrogens, antiestrogens and diet on mammary gland pubertal development and maturation will be determined. Finally, the effect of these environmental exposures on subsequent susceptibility to mammary tumor development will be determined. The overarching hypothesis is that in utero, lactational/formula feeding and post-lactational/childhood exposures to environmental stressors that affect the timing of pubertal development and sexual maturation impact on breast cancer risk. We specifically hypothesize that accelerated pubertal development and early onset of menarche increase breast cancer risk by increasing lifetime exposure to progesterone acting in concert with estrogen. To facilitate the inclusion of community concerns into Center Research Projects we will partner with community advocates and other stakeholders, and be responsive to the input from community-based, faith-based and advocacy organizations that are interested in breast cancer and environmental risks. To optimize translation of new findings into the most effective risk minimization, the Community Outreach and Translation Core will develop strategies and tools to transmit the information to populations of women and girls, as well as community stakeholders and policy-makers.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01ES012800-04
Application #
7109290
Study Section
Special Emphasis Panel (ZES1-JAB-D (BC))
Program Officer
Maull, Elizabeth A
Project Start
2003-09-29
Project End
2010-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2006
Total Cost
$761,355
Indirect Cost
Name
Michigan State University
Department
Physiology
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Wang, Weizhong; Do, Han Ngoc; Aupperlee, Mark D et al. (2018) C/EBP? LIP and c-Jun synergize to regulate expression of the murine progesterone receptor. Mol Cell Endocrinol 477:57-69
Wolff, Mary S; Pajak, Ashley; Pinney, Susan M et al. (2017) Associations of urinary phthalate and phenol biomarkers with menarche in a multiethnic cohort of young girls. Reprod Toxicol 67:56-64
Hiatt, Robert A; Stewart, Susan L; Hoeft, Kristin S et al. (2017) Childhood Socioeconomic Position and Pubertal Onset in a Cohort of Multiethnic Girls: Implications for Breast Cancer. Cancer Epidemiol Biomarkers Prev 26:1714-1721
Smith, Sandi W; Hitt, Rose; Russell, Jessica et al. (2017) Risk Belief and Attitude Formation From Translated Scientific Messages About PFOA, an Environmental Risk Associated With Breast Cancer. Health Commun 32:279-287
Deierlein, Andrea L; Wolff, Mary S; Pajak, Ashley et al. (2017) Phenol Concentrations During Childhood and Subsequent Measures of Adiposity Among Young Girls. Am J Epidemiol 186:581-592
Deierlein, Andrea L; Wolff, Mary S; Pajak, Ashley et al. (2016) Longitudinal Associations of Phthalate Exposures During Childhood and Body Size Measurements in Young Girls. Epidemiology 27:492-9
Mervish, Nancy A; Pajak, Ashley; Teitelbaum, Susan L et al. (2016) Thyroid Antagonists (Perchlorate, Thiocyanate, and Nitrate) and Childhood Growth in a Longitudinal Study of U.S. Girls. Environ Health Perspect 124:542-9
Wolff, Mary S; Teitelbaum, Susan L; McGovern, Kathleen et al. (2015) Environmental phenols and pubertal development in girls. Environ Int 84:174-80
Kale, Aarti; Deardorff, Julianna; Lahiff, Maureen et al. (2015) Breastfeeding versus formula-feeding and girls' pubertal development. Matern Child Health J 19:519-27
Wolff, M S; Teitelbaum, S L; McGovern, K et al. (2014) Phthalate exposure and pubertal development in a longitudinal study of US girls. Hum Reprod 29:1558-66

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