Purpose: The purpose of this research was to investigate the relationship between glutathione S-transferase (GST) polymorphisms and survival, and chemotherapy-related toxicity in 278 glioma patients.Experimental Design: We determined genetic variants for GSTM1, GSTT1, and GSTP1 enzymes by PCR and restriction fragment length polymorphisms. We conducted Kaplan-Meier and Cox-proportional hazard analyses to examine whether the GST polymorphisms are related to overall survival, and logistic regression analysis to explore whether the GST polymorphisms are associated with toxicity.Results: For patients with anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, and anaplastic ependymoma (n ‫؍‬ 78), patients with GSTP1*A/ *A-M1 null genotype survived longer than did the rest of the group (median survival "not achieved," and 41 months, respectively; P ‫؍‬ 0.06). Among patients treated with nitrosoureas (n ‫؍‬ 108), those with GSTP1*A/*A and GSTM1 null genotype were 5.7 times (95% confidence interval, 0.9 -37.4) more likely to experience an adverse event secondary to chemotherapy, compared with the others.Conclusions: In patients with anaplastic astrocytoma, anaplastic oligodendroglioma, and anaplastic oligoastrocytoma, combination of germ-line GSTP1*A/*A and GSTM1 null genotype confers a survival advantage. Patients with this genotype also have an increased risk of adverse events secondary to chemotherapy that primarily comprised nitrosourea alkylating agents.

Evidence for familial aggregation of glioma has been documented in both case-control and cohort studies and occurs apart from the well-described rare inherited genetic syndromes involving glioma: neurofibromatosis type 1 and 2, tuberous sclerosis, Turcot's syndrome, and Li-Fraumeni syndrome. Nonsyndromic glioma families have been studied but no genes have been identified in the two published linkage studies of familial glioma probably due to the small number of families. Because glioma is a rare but devastating cancer, and a family history of glioma has been observed in f5% of the cases, we initiated an international consortium to identify glioma families not affected by syndromes to better understand the inherited factors related to this disease. The international consortium GLIOGENE is an acronym for ''glioma gene'' and includes 15 research groups in North America, Europe, and Israel to study familial glioma. The overarching goal is to characterize genes in glioma families using a genome-wide singlenucleotide polymorphism approach and conducting linkage analysis to identify new genomic regions or loci that could harbor genes important for gliomagenesis. Here, we review the rationale for studying familial glioma and our proposed strategy for the GLIOGENE study. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1730 -4)

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gamma-Radiation-induced mutagen sensitivity of lymphocytes may be associated with an increased risk for glioma, a result that supports our earlier preliminary findings.

A small proportion of brain tumors are attributed to a genetic predisposition; however, the hereditary proportion is undetermined. This study evaluates the degree of familial aggregation of cancer in a large series of brain tumor patients. Our study included 5,088 relatives of 639 probands (3,810 first‐ and 1,278 second‐degree), diagnosed with a glioma between June 1992 and June 1995 at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, with diagnosis under age 65 years, and residents of the United States or Canada. We conducted an in‐person or telephone interview with patients and/or their next‐of‐kin, and obtained family histories for the probands’ first‐degree (parents, siblings, offspring) and selected second‐degree relatives (aunts, uncles, grandparents) using a sequential sampling strategy. Reported cancers were documented by medical records and/or death certificates (if the relative was deceased and medical records were unavailable). We conducted segregation analysis using the Pedigree Analysis Program (PAP). The analyses were divided into two categories: (1) all 639 families, and (2) a subset of families whose gliomas stained positive on p53 immunohistochemistry analysis. We demonstrated that a multifactorial Mendelian model was favored, while a model postulating a purely environmental cause of brain cancer was rejected. This study indicates that familial cancer in relatives of glioma patients are probably a result of multigenic action, and familial clustering of cancer among relatives of glioma patients may involve unknown environmental exposures. Genet. Epidemiol. 20:258–270, 2001. © 2001 Wiley‐Liss, Inc.