Pilot--Androgen Receptor Polymorphisms in African Amer. &Eastern European Women

Columbia University Health Sciences, New York NY

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Abstract

The central hypothesis of this proposal addresses the question of whether there is a significant difference in Androgen Receptor (CAG) polymorphism between cases of African American (AA) and European American(EA) women with breast cancer, and whether this difference is related to the variability in mortality rates for breast cancer between these two groups. The Androgen Receptor (AR) is expressed in female breast tissue (1,2,3) and we postulate that AR polymorphisms may occur which are specific for AA women with breast cancer. We further postulate that these specific AR polymorphisms could result in overexpression of specific hormone responsive gene in the mammary epithelium in this population of women. This may contribute to the aggressiveness of breast cancer in AA women and may have clinical implications for prognosis and treatment, as is the case with estrogen receptor (ER) status in both AA and EA breast cancer patients. A few studies have demonstrated mutation spectra of both BRCA1 and BRCA2 in AA breast cancer patients are different from those found in EA women with breast cancer (4,5,6). In a study of EA women with BRCA1 mutations, AR (CAG) n repeat lengths > 29 were associated with an earlier onset of breast cancer (7). However, another study in EA women with breast cancer found that a shorter CAG repeat length was associated with a more aggressive form of breast cancer (8). To our knowledge, the pos role of specific polymorphisms in the AR in AA women with non-hereditary breast cancer has not been examined. In addition, the role of AR (CAG) polymorphisms as a risk factor for breast cancer in AA women has also not been studied in detail. In this proposal we will compare cases of AA and EA women with breast cancer (without BRCA1 and BRCA2 mutations) for possible differences in AR (CAG) polymorphism using the polymerase chain reaction method (PCR). Differences in AR (CAG) polymorphisms may have not only a diagnostic potential in breast cancer, but there may also have clinical implications for prognosis and treatment response as seen with the ER/PR and Her2-neu receptors in breast cancer.