Genes, Hormones and Breast Cancer Risk

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DESCRIPTION (provided by applicant): Dr. Wendy Setiawan received her Ph.D. in epidemiology from UCLA in 2002. She completed a year of postdoctoral training at Harvard and is currently at the Department of Preventive Medicine at USC where she is part of the highly interactive population/cancer genetics group headed by Dr. Brian E. Henderson. The goal of this career development award is to provide Dr. Setiawan with the knowledge and necessary skills to become an independent cancer researcher. A combination of research project, structured courses, seminars, workshops, and mentoring has been designed to accomplish this goal. Two highly qualified and experienced mentors with relevant expertise, Dr. Henderson (cancer epidemiology) and Dr. Duncan Thomas (biostatistics and genetics), will supervise her training. The scientific culture and collaborative research atmosphere in the department provide an ideal environment for the candidate's academic career development. The objective of Dr. Setiawan's research project is to identify environmental and genetic determinants of circulating endogenous sex-steroid hormone levels, because there are substantial inter-individual variations in circulating hormone levels and postmenopausal women with elevated estrogens and androgens are at an increased risk of breast cancer. A cross-sectional study of healthy postmenopausal women from the Multiethnic Cohort Study (MEC) will be conducted to 1) determine whether known/potential breast cancer risk factors are associated with plasma hormone levels, 2) characterize genetic variation of estrogen biosynthesis genes (CYP11A, CYP17, CYP19, HSD3B1, HSD3B2, HSD17B1, HSD17B2, and SHBG) using a two-pronged approach (putative functional variants and inferred haplotypes) and evaluate these in relation to hormone levels; 3) develop and implement a Bayesian hierarchical statistical model that allows for an efficient and pathway-driven examination of multiple gene-gene and a priori gene-environment interactions in influencing hormone levels. The unique feature of the proposed study is that it integrates a large multiethnic population-based study, cutting edge genomic resources, and novel statistical approaches to identify genetic and environmental factors responsible for inter-individual variations in endogenous hormone levels. Identification of these factors is important to understand the mechanisms by which they could influence breast cancer risk and ultimately to identify high-risk women for prevention strategies.