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Short Communication |
Department of Epidemiology and Biostatistics [P. C., J. W., A. K-D., R. M., M. L., J. L., M. W.] and Neuropathology Unit [K. A.], School of Medicine, University of California, San Francisco, California 94143, and Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115 [K. K.]
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 CD3
-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.
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