Association of an ERCC1 Polymorphism with Adult-Onset Glioma

Association of an ERCC1 Polymorphism with Adult-Onset Glioma1

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.]

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 CD3ε-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.

Footnotes

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↵1 Supported by CA52689 and CA57220 from National Cancer Institute, ES04705 and ES06717 from National Institute of Environmental Health Sciences, Grant IRG-97-150-01-IRG from the American Cancer Society, and a grant from the National Institutes of Environmental Health Sciences, through funds provided by the United States Environmental Protection Agency. The results represent the opinions of the authors and not necessarily the official views of the Environmental Protection Agency.
↵2 To whom requests for reprints should be addressed, at Department of Epidemiology and Biostatistics, 44 Page Street, Suite 503, University of California, San Francisco, CA 94143-1215.
↵3 The abbreviations used are: SSCP, single-strand conformational polymorphism; OR, odds ratio; CI, confidence interval; ASE-1, antisense of ERCC1; CAST, CD3ε-associated signal transducer.
- Accepted May 16, 1900.
- Received July 19, 1999.
- Revision received May 3, 1900.