© 2006 by the Society for Neuro-Oncology
Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors
Fred Hutchinson Cancer Research Center and University of Washington Department of Epidemiology, Seattle, WA 98109 (A.J.D.); Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892 (N.R., P.D.I.); Core Genotyping Facility, Center for Cancer Research, National Cancer Institute, Frederick, MD 20877 (M.B.); Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709 (D.A.B., G.S.P.); St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013 (W.R.S.); Western Pennsylvania Hospital, Pittsburgh, PA 15243 (R.G.S.); Neuro-Oncology Branch, National Cancer Institute, Bethesda, MD 20892 (H.A.F.); and Brigham and Women's Hospital, Boston, MA 02115 (P.M.B.); USA
1 Address correspondence to Anneclaire J. De Roos, Fred Hutchinson Cancer Research Center and University of Washington Department of Epidemiology, 1100 Fairview Avenue N, M4-B874, Seattle, WA 98109 (deroos{at}u.washington.edu).
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Abstract |
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Genes involved in phase I and phase II regulation of aromatic hydrocarbon-induced effects exhibit sequence variability that may mediate the risk of adult brain tumors. We evaluated associations between gene variants in CYP1A1, CYP1B1, GSTM3, EPHX1, and NQO1 and adult brain tumor incidence. Cases were patients with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) diagnosed from 1994 to 1998 at three U.S. hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples collected from 1277 subjects, and genotyping was conducted for CYP1A1 I462V, CYP1B1 V432L, EPHX1 Y113H, GSTM3 *A/*B (intron 6 deletion), and NQO1 P187S. The CYP1B1 V432L homozygous variant was associated with decreased risk of meningioma (odds ratio [OR] = 0.6; 95% CI, 0.3-1.0) but not the other tumor types. The GSTM3 *B/*B genotype was associated with increased risk of glioma (OR = 2.3; 95% CI, 1.0-5.2) and meningioma (OR = 3.6; 95% CI, 1.3-9.8). Increased risks associated with GSTM3 *B/*B were observed in younger subjects (age< 50) and older subjects (age 
50), in men and women, and within each study site. The magnitude of association for GSTM3 with glioma and meningioma was greater among ever-smokers than among those who had never smoked. None of the other genotypes showed consistent associations with any tumor type. The association with the GSTM3 *B allele, while intriguing, requires replication, and additional research is needed to clarify the function of the GSTM3 alleles studied here.
Keywords: acoustic neuroma, aromatic hydrocarbons, brain tumors, gene-environment interaction, glioma, meningioma
Received March 25, 2005; Accepted September 8, 2005
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