Although the overall incidence of breast cancer is higher in Caucasian Americans (CA), the incidence of breast cancer in women below the age of 50yrs is higher in African-Americans (AA). In addition, AA women tend to present with more advanced stage breast cancer at the time of diagnosis. The underlying factors contributing to this increased incidence of early onset aggressive breast cancer are poorly understood. HYPOTHESIS: Our hypothesis is that the differences in tumor phenotype observed between African-American and Caucasian early onset breast cancer patients correlate with specific patterns of genomic aberrations. OBJECTIVE: To better understand the genetic basis for the observed racial disparities in breast cancer, chromosomal alteration and histopathologic profiles of breast tumors from Alabama AA and CA patients will be analyzed. In the long term, we seek to identify genomic loci that play a central role in the development and progression of early onset breast cancer.
SPECIFIC AIMS :
The specific aims are 1. Compare chromosomal aberration profiles in Alabama early onset breast cancer patients (Age <50yrs) using comparative genomic hybridization (CGH), 2. Characterize the histopathology of early onset breast cancer in Alabama AA and CA patients. STUDY DESIGN: Array CGH will be employed to examine chromosomal aberrations in each sample, and significant differences in copy number frequency between groups will be assessed. Pathological information will be gathered and evaluated for each ethnic group. Expression levels of known prognostic indicators (e.g., p53, p27, ER, PR and HER-2/neu) and candidate loci as revealed by array-CGH will be determined.
The proposed investigation has the potential to identify novel genes that contribute to early onset breast cancer and possibly identify new prognostic and therapeutic targets. In addition, identification of patterns of chromosomal aberration associated with specific histopathologic factors may lead to future application of the CGH technique in assessment of breast cancer prognosis. LAY STATEMENT: Compared to CA, AA have an increased incidence of early onset breast cancer with higher mortality rates. Genetic factors influencing these health disparities are poorly defined. ? ? ?
