The role of p53 mutation in BRCA1-associated ovarian cancer.

Ovarian cancer remains the most deadly gynecologic malignancy, resulting in an estimated 23,300 new cases and 13,900 deaths in the United States in the year 2002. The discovery of the BRCA1 gene in 1994 has proven to be of great interest to the study of hereditary ovarian cancer. BRCA1 gene mutation confers a 16-42% lifetime risk of the development of ovarian cancer in those affected. Although BRCA1 functions as a tumor suppressor gene, conflicting studies have shown that BRCA1 dysfunction alone may not be sufficient for tumorigenesis. p53 is a tumor suppressor gene found to be dysfunctional in nearly 50% of all human cancers and in up to 80% of ovarian malignancies. The p53 protein product plays a crucial role in DNA surveillance and repair at the Gap 1-synthesis (G1-S) cell cycle checkpoint. Studies exhibiting the interaction of BRCA1 and p53 and the role of this interaction in DNA damage response led many investigators to suggest that p53 gene mutation is required for BRCA1-associated tumor development. This review explores the evidence for BRCA1 and p53 interplay, and outlines the crucial role p53 may play in BRCA1-related ovarian cancer.