A pivotal role for estrogens in breast cancer etiology has been known for decades. In women, the source of estrogens varies by menopausal status. The ovaries are the predominant source before menopause and peripheral conversion of androgens that are secreted by the ovaries and adrenals is the predominant source after menopause. Ovarian steroid hormone synthesis is complex and is intimately related to the underlying process of ovarian folliculogenesis. Anti-Mullerian Hormone (AMH) is a key regulator of ovarian folliculogenesis, and we recently observed a highly significant increased risk of breast cancer associated with elevated serum AMH levels. Genetics is a major determinant of ovarian function. The primary specific aim of the proposed study is to determine if putative functional polymorphisms and haplotype tagging SNPs (htSNPs) in the AMH gene and genes that encode its type 1 (ACVR1) and type 2 receptors (AMHR2) are associated with breast cancer risk. The study will be conducted using resources previously collected in the Women's Insights and Shared Experiences Study (WISE), which was a population-based case-control study conducted in the Philadelphia area. WISE included 878 cases and 1409 frequency matched controls who provided questionnaire data and DNA. Genotyping will be conducted on the Sequenom platform. The association of AMH, ACVR1 and AMHR2 genotype with breast cancer risk will be evaluated primarily using unconditional logistic regression.

Public Health Relevance

Public Health Relevance

TO PUBLIC HEALTH We recently observed a highly significant increased risk of breast cancer in women with elevated serum levels of anti-mullerian hormone (AMH). Identification of the underlying genetic basis for this association could substantially increase our understanding of breast cancer etiology. Ultimately, results could lead to identification of women at increased risk of breast cancer, advances in screening for detection of women at increased risk and development of interventions to lower risk in susceptible women.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA150072-01
Application #
7897148
Study Section
Special Emphasis Panel (ZCA1-SRLB-D (J1))
Program Officer
Nelson, Stefanie A
Project Start
2010-04-01
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
1
Fiscal Year
2010
Total Cost
$87,250
Indirect Cost
Name
Fox Chase Cancer Center
Department
Type
DUNS #
073724262
City
Philadelphia
State
PA
Country
United States
Zip Code
19111
Nan, Hongmei; Dorgan, Joanne F; Rebbeck, Timothy R (2015) Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans. Int J Mol Epidemiol Genet 6:33-40