Serum IgE, tumor epidermal growth factor receptor expression, and inherited polymorphisms associated with glioma survival.
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.
Wrensch
Margaret
M
Department of Neurological Surgery, University of California San Francisco, San Francisco, California 94102, USA. margaret.wrensch@ucsf.edu
Wiencke
John K
JK
Wiemels
Joe
J
Miike
Rei
R
Patoka
Joe
J
Moghadassi
Michelle
M
McMillan
Alex
A
Kelsey
Karl T
KT
Aldape
Kenneth
K
Lamborn
Kathleen R
KR
Parsa
Andrew T
AT
Sison
Jennette D
JD
Prados
Michael D
MD
D001254:Astrocytoma / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D005909:Glioblastoma / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008875:Middle Aged; D011110:Polymorphism, Genetic
D014408:Biomarkers, Tumor; D007073:Immunoglobulin E; D066246:ErbB Receptors