Publications (2)11.98 Total impact
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Article: Ethnicity delineates different genetic pathways in malignant glioma.
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ABSTRACT: In the United States and the San Francisco Bay Area, whites are nearly twice as likely as non-whites to develop brain cancer. To test whether prevalence and types of alterations in the p53 pathway in brain tumor development may 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 San 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 non-whites with astrocytic glioma by PCR-single-strand conformation polymorphism and direct sequencing. Tumor P53 protein (TP53) immunohistochemistry (IHC) available for 164 of these cases showed that tumors from 50% (13 of 26) of non-whites and 32% (44 of 138) of whites contained intense IHC staining for TP53, indicating persistence of TP53 protein. Irrespective of IHC status, tumors from 42% (11 of 26) of non-whites versus 13% (19 of 146) of whites contained p53 mutations (age/gender-adjusted odds ratio, 5.7; 95% confidence interval, 2.2-15.1; P = 0.0004). Patients with p53 mutation-positive tumors were also significantly younger than patients with mutation-negative tumors and somewhat more likely to be female. A higher proportion of tumors from non-whites than from whites had transition mutations, but there were similar proportions of transversion mutations in tumors from whites and non-whites. Whites and non-whites also had similar 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 whites 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.Cancer Research 06/2001; 61(10):3949-54. · 7.86 Impact Factor -
Article: Association of an ERCC1 polymorphism with adult-onset glioma.
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ABSTRACT: Gliomas include several histologically distinct types of tumors whose molecular profiles suggest different etiologies. Because the ERCC1 protein is essential for nucleotide excision repair and influences genomic instability, polymorphisms in ERCC1 may play a role in human tumors. We determined the presence of the A versus C polymorphism at nucleotide 8092 of ERCC1 using a single-strand conformational polymorphism assay and DNA sequencing in adults with glioma and controls from a population-based study. Among 318 alleles from 159 controls, 27% (86) were A and 73% were C. Prevalences of the CC genotype were 51% (81 of 159), 48% (30 of 62), 63% (20 of 32), and 82% (23 of 28) for controls and subjects with glioblastoma multiforme, astrocytoma, and oligoastrocytoma, respectively (Fisher's exact P = 0.009). The age-adjusted odds ratio for genotype CC in all cases versus controls was 1.4 (95% confidence interval, 0.9-2.3), whereas that for subjects with oligoastrocytoma versus controls was 4.6 (95% confidence interval, 1.6-13.2). The median age at diagnosis was 46 years for glioma patients with the CC genotype compared with 54 years for patients with the AA or AC genotype (P = 0.04). This is the first study to report a significant association of a polymorphism in ERCC1 with the risk of brain tumors. This A/C polymorphism, which may affect mRNA stability for ERCC1, also results in an amino acid substitution of lysine to glutamine in a recently described nucleolar protein (ASE-1) and T-cell receptor complex subunit CD3epsilon-associated signal transducer (CAST). This finding, if confirmed in other series, may provide a foundation on which to study novel mechanisms of carcinogenesis in subsets of glioma.Cancer Epidemiology Biomarkers & Prevention 09/2000; 9(8):843-7. · 4.12 Impact Factor
