Genetic Polymorphisms in GSTM1, -P1, -T1, and CYP2E1 and the Risk of Adult Brain Tumors
- Anneclaire J. De Roos1,
- Nat Rothman,
- Peter D. Inskip,
- Martha S. Linet,
- William R. Shapiro,
- Robert G. Selker,
- Howard A. Fine,
- Peter M. Black,
- Gary S. Pittman and
- Douglas A. Bell
- Division of Cancer Epidemiology and Genetics [A. J. D., N. R., P. D. I., M. S. L.] and Neuro-oncology Branch [H. A. F.], National Cancer Institute, Bethesda, Maryland 20892-7240; St. Joseph’s Hospital and Medical Center, Phoenix, Arizona [W. R. S.]; Western Pennsylvania Hospital, Pittsburgh, Pennsylvania [R. G. S.]; Brigham and Women’s Hospital, Boston, Massachusetts [P. M. B.]; and Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina [G. S. P., D. A. B.]
Abstract
GST and CYP2E1 genes are involved in metabolism of several compounds (e.g., solvents) that may play a role in brain cancer etiology. We evaluated associations between polymorphisms in these genes and adult brain tumor incidence. Cases were 782 patients with brain tumors diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples that had been collected from 1277 subjects (80% of all subjects; 604 controls; 422 gliomas, 172 meningiomas, and 79 acoustic neuromas), and genotyping was successfully conducted for GSTM1 null, GSTT1 null, GSTP I105V, GSTP A114V, CYP2E1 RsaI, and CYP2E1 Ins96. The GSTP1 105 Val/Val genotype was associated with increased glioma incidence [odds ratio (OR), 1.8; 95% confidence limits (CLs), 1.2, 2.7], with the estimated effect following a trend of increasing magnitude by number of variant alleles (Ile/Ile: OR, 1.0; Ile/Val: OR, 1.3; Val/Val: OR, 2.1). The CYP2E1 RsaI variant was weakly associated with glioma (OR, 1.4; 95% CL, 0.9, 2.4) and acoustic neuroma (OR, 2.3; 95% CL, 1.0, 5.3), with some indication of stronger associations among younger subjects. Estimated effects of the gene variants differed by glioma subtype. There was evidence of supermultiplicativity of the joint effect of GSTP1 I105V and CYP2E1 RsaI variants on both glioma and acoustic neuroma, even following adjustment of estimates toward a common prior distribution using hierarchical regression models. Previously reported associations between the GSTT1 null genotype and overall glioma incidence were not replicated, but an association with meningioma was observed (OR, 1.5; 95% CL, 1.0, 2.3). These findings may provide clues to both genetic and environmental determinants of brain tumors.
Footnotes
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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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↵1 To whom requests for reprints should be addressed, at National Cancer Institute, 6120 Executive Boulevard, EPS 8109, Bethesda, MD 20892-7240. Phone: (301) 594-7901; Fax: (301) 402-1819; E-mail: deroosa{at}mail.nih.gov
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↵2 The abbreviations used are: GST, glutathione S-transferase; CYP, cytochrome P450; NIEHS, National Institute of Environmental Health Sciences; OR, odds ratio; CL, confidence limit.
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- Accepted October 29, 1902.
- Received November 30, 1901.
- Revision received October 9, 1902.
