A POPULATION-BASED CASE-CONTROL STUDY OF THE CYP2D6 AND GSTT1 POLYMORPHISMS AND MALIGNANT BRAIN-TUMORS

Previous studies of associations of metabolic polymorphisms with the o ccurrence of malignant brain tumors have suggested that there is a sig nificantly increased risk of development of adult gliomas in individua ls who carry a poor metabolizer CYP2D6 variant allele and the GSTT1 nu ll genotype. To investigate this further, a population-based case cont rol study of adult glioma in the San Francisco Bay area was conducted. Patients (n = 188) diagnosed with brain tumors and controls (n = 166) were enrolled using random digit dialing and were frequency matched f or age, ethnicity and gender. Genotyping for the polymorphisms was per formed using standard PCR-based techniques. The analysis of the data w as restricted to Caucasians because the prevalence of these traits is known to vary by ethnicity. No overall association of either the GSTT1 null genotype or CYP2D6 homozygous variant PM genotype was observed w ith the occurrence of brain tumors. However, when stratified by histop athologic subtype, there was a significantly increased risk for oligod endroglioma associated with the GSTT1 null genotype, with an OR of 3.2 (95% CI 1.1-9.2). These data suggest that the GSTT1 polymorphism may play a role in the development of a subset of malignant brain tumors i n adults, and indicate the need for further studies.