Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors.
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 > or = 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.
De Roos
Anneclaire J
AJ
Fred Hutchinson Cancer Research Center and University of Washington Department of Epidemiology, Seattle, WA 98109, USA. deroos@u.washington.edu
Rothman
Nathaniel
N
Brown
Merideth
M
Bell
Douglas A
DA
Pittman
Gary S
GS
Shapiro
William R
WR
Selker
Robert G
RG
Fine
Howard A
HA
Black
Peter M
PM
Inskip
Peter D
PD
D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000235:genetics*; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000378:metabolism*; D008297:Male; D008579:Meningioma / Q000235:genetics*; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009464:Neuroma, Acoustic / Q000235:genetics*; D012307:Risk Factors
D006841:Hydrocarbons, Aromatic; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D004851:Epoxide Hydrolases