Ethnicity delineates different genetic pathways in malignant glioma

In the United States and the San Francisco Bay Area, whites are nearly twic e as likely as non-whites to develop brain cancer. To test whether prevalen ce and types of alterations in the p53 pathway in brain tumor development m ay explain some of this difference in risk, we have analyzed the p53 status of astrocytic gliomas from a population-based sample of cases within our S an Francisco Bay Area Adult Glioma Study. We identified mutations in exons 5-8 of p53 using DNA extracted from formalin-fixed paraffin-embedded tissue blocks from 146 whites and 26 cion-whites with astrocytic glioma by PCR-si ngle-strand conformation polymorphism and direct sequencing. Tumor P53 prot ein (TP53) immunohistochemistry (IHC) available for 164 of these cases show ed that tumors from 50% (13 of 26) of non-whites and 32% (44 of 138) of whi tes contained intense IHC staining for TP53, indicating persistence of TP53 protein. Irrespective of IHC status, tumors from 42% (11 of 26) of non-whi tes versus 13% (19 of 146) of whites contained p53 mutations (age/gender-ad justed odds ratio, 5.7; 95% confidence interval, 2.2-15.1; P = 0.0004). Pat ients with p53 mutation-positive tumors were also significantly younger tha n patients with mutation-negative tumors and somewhat more likely to be fem ale. A higher proportion of tumors from non-whites than from whites had tra nsition mutations, but there were similar proportions of transversion mutat ions in tumors from whites and non-whites. Whites and non-whites also had s imilar proportions of tumors with p53 mutations that stained intensely for TP53 (78 and 82%, respectively). Because whites have higher risk for glioma than non-whites in this population, that the gliomas from whites were less likely than those from non-whites to have p53 mutation suggests that white s may be more likely than non-whites to be at risk for the more common type of astrocytic gliomas, which do not contain p53 mutations.