Oxidative response gene polymorphisms and risk of adult brain tumors.
Oxidative stress is believed to play a key role in tumor formation. Although this mechanism could be especially pertinent for brain tumors given the high oxygen consumption of the brain, very little has been published regarding brain tumor risk with respect to genes mediating oxidative stress. Using data from non-Hispanic whites in a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n=362), meningioma (n=134), and acoustic neuroma (n=69) compared to noncancer controls (n=494) with respect to nine single nucleotide polymorphisms from seven genes involved in oxidative stress response (CAT, GPX1, NOS3, PON1, SOD1, SOD2, and SOD3). We observed increased risk of glioma (odds ratio [OR](CT/CC)=1.3; 95% confidence interval [95% CI], 1.0-1.7) and meningioma (OR(CT/CC)=1.7; 95% CI, 1.1-2.7) with the C variant of SOD3 rs699473. There was also indication of increased acoustic neuroma risk with the SOD2 rs4880 Ala variant (OR(CT/CC)=2.0; 95% CI, 1.0-4.2) and decreased acoustic neuroma risk with the CAT rs1001179 T allele variant (OR(CT/TT)=0.6; 95% CI, 0.3-1.0). These relationships persisted when major groups of disease controls were excluded from the analysis. Our results suggest that common variants in the SOD2, SOD3, and CAT genes may influence brain tumor risk.
Rajaraman
Preetha
P
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-7238, USA. rajarama@mail.nih.gov
Hutchinson
Amy
A
Rothman
Nathaniel
N
Black
Peter M
PM
Fine
Howard A
HA
Loeffler
Jay S
JS
Selker
Robert G
RG
Shapiro
William R
WR
Linet
Martha S
MS
Inskip
Peter D
PD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002374:Catalase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics*; D000099156:Superoxide Dismutase 2
D002374:Catalase; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C441642:SOD3 protein, human