RACIAL DISPARITY IN THE ASSOCIATION OF P53 GENE ALTERATIONS WITH BREAST-CANCER SURVIVAL

A significant black/white difference in breast cancer prognosis has be en observed in the United States. Alterations of p53 tumor suppressor gene in breast cancer have been associated with poor prognosis. This s tudy was designed to test the hypothesis that p53 gene alterations are related to the difference in prognosis between black and white breast cancer patients. Formalin-fixed paraffin-embedded breast tissue block s were available from 45 black and 47 white patients for PCR-single st rand conformation polymorphism analysis and DNA sequencing. The types of p53 gene alterations were compared between blacks and whites. Assoc iations between p53 gene alterations and survival were also evaluated. Three missense, 2 nonsense, 1 microdeletion, 1 intron, and 4 silent m utations were detected in blacks, while 7 missensc, 1 microdeletion, 1 silent mutation, and 3 polymorphisms were observed in whites. Among t he point mutations, G:C to A:T transitions at non-CpG sites mere found in 80.0% of blacks (8 of 10) and 63.5% of whites (5 of 8). Significan tly poorer survival associated with p53 gene alterations was observed for blacks (P = 0.012), but not for whites, Black patients with p53 al terations had a significant 4-5-fold excess risk of death from breast cancer than those without p53 alterations. Adjustment for stage, age, tumor histopathology, receptor status, and adjuvant treatment did not change the excess risk. The findings suggest that the types of p53 gen e alterations may contribute to the racial difference in breast cancer survival.