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Genetic Polymorphisms of Glutathione S-Transferases and the Risk of Adult Brain Tumors: A Meta-analysis

Departments of ¹ Clinical Epidemiology and Biostatistics and ² Neurosurgery, McMaster University; ³ Juravinski Cancer Center; and ⁴ Center for the Evaluation of Medicine, St. Joseph Healthcare, Hamilton, Ontario, Canada

Requests for reprints: Rose Lai, The Neurological Institute of Columbia University Division of Neuro-oncology, 710 West 168^th Street 2^nd Floor New York, NY 10032. Phone: (212) 305-1718; Fax: (212) 305-1716. E-mail: lairk{at}mcmaster.ca

Background: Studies investigating the association between genetic polymorphisms of glutathione S-transferases (GST) and risk of adult brain tumors have reported conflicting results. The rationale of this meta-analysis was to determine whether GST variants increase the susceptibility of adult brain tumors by pooling data.

Methods: Two investigators independently searched the HuGENet database, MEDLINE, EMBASE, conference articles, and manually reviewed bibliographies of retrieved articles. Papers were included if they were observational studies investigating the influence of GSTM1, GSTT1, GSTP1 I105V, or GSTP1 A114V on the development of adult brain cancers. Potential sources of heterogeneity between studies were explored in a meta-regression.

Results: We identified eight eligible studies, which included 1,630 cases of glioma, 245 cases of meningioma, and 7,151 controls. Using the random effects model, there was no association between any of the GST variants and the risk of glioma [overall odds ratio (OR), 1.08; 95% confidence interval (95% CI), 0.95-1.22]. Subgroup analyses also showed no relationship between GST variants and histopathologic groups; the overall ORs were 1.13 (95% CI, 0.88-1.43) for high-grade glioma and 1.08 (95% CI, 0.76-1.55) for low-grade glioma. A random effects meta-regression suggested that the use of in-hospital controls produced larger effect estimates in glioma than the use of population controls (overall OR, 1.30; 95% CI, 1.03-1.65). The T1 null genotype was significantly associated with a risk of meningioma (OR, 1.95; 95% CI, 1.02-3.76), but the M1 variant was not.

Conclusion: This study did not suggest any relationship between GST variants and risks of glioma; the T1 null genotype may influence the susceptibility of meningioma, but larger studies are needed to substantiate this relationship.

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