An international case-control study of glutathione transferase and functionally related polymorphisms and risk of primary adult brain tumors.
BACKGROUND
Glutathione transferases (GST) detoxify environmental and endogenous compounds and levels of two polymorphic GST proteins, GSTM3 and GSTP1, are high in the brain. Previous studies of GSTM3 and GSTP1 polymorphisms and adult brain tumor risk have produced inconsistent results, whereas the GSTM3 -63 variant is newly identified and, therefore, has not yet been studied in this context. We therefore examined associations between GSTM3 -63, GSTM3 *A/*B, GSTP1 105, and GSTP1 114 variants and adult brain tumor risk and the interaction of the effects of these same polymorphisms with cigarette smoking. In addition, the enzymes NQO1 and CYP1A1 alter susceptibility to oxidative brain damage. Because there is less previous evidence for a role of NQO1, CYP1A1, GSTM1, and GSTT1 variants, we restricted analysis of these variants to a small preliminary study.


METHODS
We genotyped DNA collected for an international population-based case-control study of 725 glioma cases, 329 of which were glioblastoma cases, 546 meningioma cases and 1,612 controls. Study participants were residents of Sweden, southeast England, Denmark, and Finland.


RESULTS
We found no associations between the GSTM3, GSTP1, NQO1, CYP1A1, GSTM1, or GSTT1 polymorphisms and adult brain tumor risk with the possible exception of a weak association between the G-C (Val-Ala) GSTP1 105/114 haplotype and glioma [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54, 0.99], nor was there an interaction between the effects of the GSTM3 or GSTP1 polymorphisms and cigarette smoking.


CONCLUSIONS
Overall, we observed no strong evidence for an association between GST or related enzyme polymorphisms and adult brain tumor risk.
Schwartzbaum
Judith A
JA
Division of Epidemiology and Biometrics, School of Public Health, Ohio State University, Starling-Loving Hall, 320 W. Tenth Avenue, Columbus, OH 43210, USA. schwartzbaum.1@osu.edu
Ahlbom
Anders
A
Lönn
Stefan
S
Warholm
Margareta
M
Rannug
Agneta
A
Auvinen
Anssi
A
Christensen
Helle Collatz
HC
Henriksson
Roger
R
Johansen
Christoffer
C
Lindholm
Carita
C
Malmer
Beatrice
B
Salminen
Tiina
T
Schoemaker
Minouk J
MJ
Swerdlow
Anthony J
AJ
Feychting
Maria
M
D000293:Adolescent; D000328:Adult; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D004739:England / Q000453:epidemiology; D005260:Female; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D011110:Polymorphism, Genetic; D011159:Population Surveillance; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013548:Sweden / Q000453:epidemiology
D019363:Cytochrome P-450 CYP1A1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D005982:Glutathione Transferase