An International Case-Control Study of Glutathione Transferase and Functionally Related Polymorphisms and Risk of Primary Adult Brain Tumors
- Judith A. Schwartzbaum1,2,3,
- Anders Ahlbom3,
- Stefan Lönn3,
- Margareta Warholm4,
- Agneta Rannug4,
- Anssi Auvinen5,6,
- Helle Collatz Christensen7,
- Roger Henriksson8,
- Christoffer Johansen7,
- Carita Lindholm6,
- Beatrice Malmer8,
- Tiina Salminen5,6,
- Minouk J. Schoemaker9,
- Anthony J. Swerdlow9 and
- Maria Feychting3
- 1Division of Epidemiology, School of Public Health, and 2Comprehensive Cancer Center, Ohio State University, Columbus, Ohio; 3Division of Epidemiology and 4Division of Work Environment Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 5Department of Epidemiology, Tampere School of Public Health, University of Tampere, Finland; 6Department of Research and Environmental Surveillance, Radiation and Nuclear Safety Authority, STUK-, Helsinki, Finland; 7Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; 8Department of Radiation Sciences, Oncology, Umeå University Hospital, Umeå, Sweden; and 9Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey, United Kingdom
- Requests for reprints:
Judith Schwartzbaum, Division of Epidemiology and Biometrics, School of Public Health, Ohio State University, Starling-Loving Hall, 320 W. Tenth Avenue, Columbus, OH 43210. Phone: 614-268-1548; Fax: 614-293-3937. E-mail: schwartzbaum.1{at}osu.edu
Abstract
Background: 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.
Methods: 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.
Results: 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.
Conclusions: Overall, we observed no strong evidence for an association between GST or related enzyme polymorphisms and adult brain tumor risk. (Cancer Epidemiol Biomarkers Prev 2007;16(3):559–65)
- glutathione transferase
- single nucleotide polymorphisms
- haplotype analysis
- Brain/central nervous system cancers
Footnotes
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Grant support: Nordic Cancer Union. All centers were also supported by the European Commission Fifth Framework Program “Quality of Life and Management of Living Resources” (Contract QLK4-CT-1999-01563) and the Unio Internationale Contra Cancrum (UICC; RCA/01/08). The UICC received funds for this study from the Mobile Manufacturers' Forum and the Global System for Mobile Communications Association. Provision of funds to the Interphone study investigators via UICC was governed by agreements that guaranteed Interphone's complete scientific independence. These agreements are publicly available at http://www.iarc.fr/ENG/Units/RCAd.html. The Swedish center was also supported by the Swedish Research Council, the Swedish Cancer Society, and the Cancer Research Foundation in Northern Sweden; the Danish center was supported by the Danish Cancer Society; the Finnish center was supported by the Cancer Society of Finland, the Emil Aaltonen Foundation, and the Academy of Finland; and the United Kingdom center was supported by the Mobile Telecommunications and Health Research Program. The views expressed in the publication are those of the authors and not necessarily those of the funders.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted January 5, 2007.
- Received October 30, 2006.
- Revision received December 4, 2006.
