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Clinical Investigations |
1 Fred Hutchinson Cancer Research Center and University of
Washington Department of Epidemiology
2 Division of Cancer Epidemiology and Genetics, National
Cancer Institute
3 Core Genotyping Facility, Center for Cancer Research,
National Cancer Institute
4 Laboratory of Computational Biology and Risk Analysis,
National Institute of Environmental Health Sciences
5 St. Joseph's Hospital and Medical Center,
Phoenix
6 Western Pennsylvania Hospital, Pittsburgh
7 Neuro-Oncology Branch, National Cancer
Institute
8 Brigham and Women's Hospital, Boston
* To whom correspondence should be addressed. E-mail: 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.
Key Words: acoustic neuroma, aromatic hydrocarbons, brain tumors, gene-environment interaction, glioma, meningioma
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