This study is predicated on the hypotheses that endogenous and exogenous factors can lead to the production or selection of genomic structural changes in susceptible breast epithelial cells and that these changes in turn affect phenotype and behavior of breast cancers. This project brings together an interdisciplinary team skilled in genomics, pathology, epidemiology, biostatistics and clinical research to: 1) identify frequent losses and gains of genetic material using array CGH analysis on a large set of purified breast tumor samples and 2) determine the relationship between specific regions of copy number change and particular patient and tumor attributes. The identification of altered chromosomal regions in breast tumors in relation to race, risk factors, tumor characteristics and breast cancer survival is an important step toward understanding the underlying biology and clinical behavior of the disease in African American and white women. To specifically address our overall goals, we will: 1) use array-based CGH methods to identify chromosomal regions that show frequent amplification and/or deletion in tumors of 398 women (307 Caucasian and 91 African American), 2) examine the association between genetic changes race, risk factors, patient characteristics and breast cancer survival, and 3) use high-resolution arrays to refine candidate regions that are associated with risk factors or survival. ? ?
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