The Role of BRCA1 in Lethal Prostate Cancer

Abstract : BRCA1 is involved in DNA maintenance and repair as well as in cell cycle control. We hypothesized that activation of BRCA1 in prostate tumors is a consequence of an increased proliferation rate as a compensatory mechanism of tumor cells to allow DNA repair in highly replicating cells. As such, tumor expression of BRCA1 is a marker of lethal prostate cancer. In a recently submitted manuscript, we confirmed our previous results that BRCA1 positive tumors are characterized by an aggressive, lethal phenotype and increased indices of apoptosis and cell proliferation in a large cohort of men with prostate cancer from the Health Professionals Follow-up Study. Moreover, in preliminary analyses we see that genetic variation in BRCA1 captured by tagging SNPs is associated with increased risk of lethal cancer. We plan to correlate BRCA1 status in tumors with expression of cell cycle regulators, p27 and p21. This project s goals are to identify biomarkers of progression by examining BRCA1 tumor status and cancer mortality, as well as to understand aspects of tumor biology associated with BRCA1.