Glutathione-S-transferase variants and adult glioma

Abstract

Introduction: Conflicting findings have been reported for associations of primary brain tumors and constitutive polymorphisms in glutathione-S-transferases (GSTs). Methods: We genotyped population-based cases ascertained through rapid case ascertainment and controls identified through random-digit dialing in the San Francisco Bay Area between 1991-1994 (series 1) and 1997-2000 (series 2) for homozygous deletion or presence of GSTM1 (μ) and GSTT1 (θ) genes and for two variants in GSTP (π; i.e., I105V and A114V). A single neuropathologist for each series determined histological type. Blood or buccal swabs were obtained from about 53.8% of cases and 64.6% of controls. Case-control genotype frequencies were compared overall and by histological type and by age group (≤40, 41-60, and >60), gender, and series. Results: Among whites, 367 cases (179 glioblastoma, 62 other astrocytoma, 94 oligodendroglioma or oligoastrocytoma, and 32 other histologies) and 428 controls were genotyped for all four polymorphisms. Multivariate logistic models including the four GST loci, age, gender (except in gender-specific models), and series showed no significant case-control differences for GST genotypes. Among cases over age 60, prevalence of GSTP I105V Val/Val was 6.4% of 108 cases versus 15% of 176 controls [odds ratio (OR) 0.38; 95% confidence interval (CI) 0.15-0.93; P = 0.03]. GSTT1 deletion was nearly significantly more common among glioblastoma cases with tumor p53 mutation than for those whose tumors did not have p53 mutation (OR 2.8; 95% CI 0.93-8.4; P = 0.07). Conclusions: There is little evidence for associations of GST variants with major glioma histological subtypes, but GST polymorphisms might influence certain molecular subtypes or progression.