The overall goal of this project is the identification of breast cancer gene expression profiles in African Americans and Caucasians and the translation of this information into clinical markers for prognosis, treatment, and targets for therapy design. Breast cancer mortality is higher in African Americans than in Caucasians because of the late stage of disease on diagnosis, aggressive estrogen receptor-negative and poorly-differentiated tumors, and early onset breast cancer. The hypothesis to be tested is that breast cancers in African American and Caucasians are characterized by many common but some distinct molecular alterations that result in altered patterns of gene expression and differences in clinical presentation and behavior. Prominent changes in gene expression will be identified in primary invasive breast cancers stratified and compared by age, estrogen receptor (ER) status, tumor differentiation, and race using customized cDNA microarray filters containing preselected genes important in breast cancer pathogenesis. Expression profiles will also be derived between primary tumors and tumors and lymph node metastasis from both populations by microarray analysis. We will identify clusters of co-expressing genes associated with specific subsets of the disease. These results will enable the development of a comparative molecular profiles for African American and Caucasian breast cancer, and a progression model for breast cancer based on molecular alterations. Our previous SAGE analysis identified several gene alterations in breast cancer. Quantitative reverse transcriptase polymerase chain reaction of over-expressed genes (Claudin-7, BRCG-1) and methylation-specific PCR analysis of under- expressed genes (cyclin D2, RARbeta2, Twist and ER) will be used to investigate the association between these highly affected markers and clinical/pathological characteristics, such as estrogen receptor status, tumor differentiation, age of onset, metastasis, and survival in African Americans compared to Caucasians. These studies will enable the development of markers useful for early detection, prevention, prognosis and treatment of breast cancer.
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