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Serum IgE, Tumor Epidermal Growth Factor Receptor Expression, and Inherited Polymorphisms Associated with Glioma Survival

¹ Department of Neurological Surgery and ² Comprehensive Cancer Center Biostatistics Core, University of California San Francisco, San Francisco, California; ³ Department of Genetics and Complex Diseases, Harvard School of Public Health, Harvard University, Boston, Massachusetts; and ⁴ Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Margaret Wrensch, Department of Neurological Surgery, University of California San Francisco, Suite 503, 44 Page Street, San Francisco, CA 94102. Fax: 415-502-1787; E-mail: margaret.wrensch{at}ucsf.edu.

In population-based glioma patients, we examined survival in relation to potentially pertinent constitutive polymorphisms, serologic factors, and tumor genetic and protein alterations in epidermal growth factor receptor (EGFR), MDM2, and TP53. Subjects were newly diagnosed adults residing in the San Francisco Bay Surveillance Epidemiology and End Results Area during 1991 to 1994 and 1997 to 1999 with central neuropathology review (n = 873). Subjects provided blood for serologic studies of IgE and IgG to four herpes viruses and constitutive specimens for genotyping 22 polymorphisms in 13 genes (n = 471). We obtained 595 of 697 astrocytic tumors for marker studies. We determined treatments, vital status, and other factors using registry, interview, medical record, and active follow-up data. Cox regressions for survival were adjusted for age, gender, ethnicity, study series, resection versus biopsy only, radiation, and chemotherapy. Using a stringent P < 0.001, glioma survival was associated with ERCC1 C8092A [hazard ratio (HR), 0.72; 95% confidence limits (95% CL), 0.60-0.86; P = 0.0004] and GSTT1 deletion (HR, 1.64; 95% CL, 1.25-2.16; P = 0.0004); glioblastoma patients with elevated IgE had 9 months longer survival than those with normal or borderline IgE levels (HR, 0.62; 95% CL, 0.47-0.82; P = 0.0007), and EGFR expression in anaplastic astrocytoma was associated with nearly 3-fold poorer survival (HR, 2.97; 95% CL, 1.70-5.19; P = 0.0001). Based on our and others' findings, we recommend further studies to (a) understand relationships of elevated IgE levels and other immunologic factors with improved glioblastoma survival potentially relevant to immunologic therapies and (b) determine which inherited ERCC1 variants or other variants in the 19q13.3 region influence survival. We also suggest that tumor EGFR expression be incorporated into clinical evaluation of anaplastic astrocytoma patients. (Cancer Res 2006; 66(8): 4531-41)

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