An international case-control study of glutathione transferase and functionally related polymorphisms and risk of primary adult brain tumors.

Division of Epidemiology and Biometrics, School of Public Health, Ohio State University, Starling-Loving Hall, 320 W. Tenth Avenue, Columbus, OH 43210, USA. schwartzbaum.1@osu.edu

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2007 Mar

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Glutathione transferases (GST) detoxify environmental and endogenous compounds and levels of two polymorphic GST proteins, GSTM3 and GSTP1, are high in the brain. Previous studies of GSTM3 and GSTP1 polymorphisms and adult brain tumor risk have produced inconsistent results, whereas the GSTM3 -63 variant is newly identified and, therefore, has not yet been studied in this context. We therefore examined associations between GSTM3 -63, GSTM3 *A/*B, GSTP1 105, and GSTP1 114 variants and adult brain tumor risk and the interaction of the effects of these same polymorphisms with cigarette smoking. In addition, the enzymes NQO1 and CYP1A1 alter susceptibility to oxidative brain damage. Because there is less previous evidence for a role of NQO1, CYP1A1, GSTM1, and GSTT1 variants, we restricted analysis of these variants to a small preliminary study. We genotyped DNA collected for an international population-based case-control study of 725 glioma cases, 329 of which were glioblastoma cases, 546 meningioma cases and 1,612 controls. Study participants were residents of Sweden, southeast England, Denmark, and Finland. We found no associations between the GSTM3, GSTP1, NQO1, CYP1A1, GSTM1, or GSTT1 polymorphisms and adult brain tumor risk with the possible exception of a weak association between the G-C (Val-Ala) GSTP1 105/114 haplotype and glioma [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54, 0.99], nor was there an interaction between the effects of the GSTM3 or GSTP1 polymorphisms and cigarette smoking. Overall, we observed no strong evidence for an association between GST or related enzyme polymorphisms and adult brain tumor risk.

Citation

Judith A Schwartzbaum, Anders Ahlbom, Stefan Lönn, Margareta Warholm, Agneta Rannug, Anssi Auvinen, Helle Collatz Christensen, Roger Henriksson, Christoffer Johansen, Carita Lindholm, Beatrice Malmer, Tiina Salminen, Minouk J Schoemaker, Anthony J Swerdlow, Maria Feychting. An international case-control study of glutathione transferase and functionally related polymorphisms and risk of primary adult brain tumors. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2007 Mar;16(3):559-65