Abstract
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.
Highlights
About 14,000 people are diagnosed with and >10,000 die from glioma each year in the United States [1]
The study group consisted of 873 glioma subjects: 519 with glioblastoma, 105 with anaplastic astrocytoma, and the remaining with other histologic types (Table 2)
The following polymorphisms were not associated with glioma, glioblastoma, or anaplastic astrocytoma survival with P > 0.10: ERCC2 K751Q and R156R, GSTM1 deletion, GSTP1 I105V and A114V, IL4 C34T, MEH H113Y, MGMT I143V, and XRCC1 H280R
Summary
About 14,000 people are diagnosed with and >10,000 die from glioma each year in the United States [1]. Primary brain and central nervous system (CNS) tumors rank first among cancer types for the average years of life lost with an average of 20.1 years Histologic type and grade, age, extent of resection, tumor location, radiation therapy, some chemotherapy protocols, Karnofsky performance status, and other functionality measures have been consistently and convincingly linked to glioma survival [3, 4]. Investigators are currently trying to identify and understand tumor markers or patient characteristics that might influence survival or response to treatment Patients with long-term survival, uncommon for glioblastoma, could provide important clues to identify key pathways for developing future therapies
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