Grant Number:	5R03CA150072-02 Interpret this number
Primary Investigator:	Dorgan, Joanne
Organization:	Fox Chase Cancer Center
Project Title:	Anti-Mullerian Hormone Genes and Breast Cancer Risk
Fiscal Year:	2011

DESCRIPTION (provided by applicant): ABSTRACT 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: 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.





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