Increased frequency of rapid acetylator genotypes in patients with brain astrocytoma and meningioma.
OBJECTIVE
The arylamine N-acetyltransferase (NAT2) is a polymorphic enzyme involved in deactivation and activation of carcinogens through N- and O-acetylation. We investigated the association between the genetic NAT2 polymorphism and brain tumors by analysis of genomic DNA from 71 brain tumor patients and 258 healthy controls.


METHODS
Seven single nucleotide polymorphisms of the NAT2 gene were studied by using allele-specific polymerase chain reaction amplification.


RESULTS
Ten different NAT2 allelic variants were identified in both patient and control groups. A higher number of individuals carrying functional NAT2 genes, and therefore with a rapid acetylation phenotype, was found in brain tumor patients vs healthy volunteers (OR 1.79, 95% CI 1.05-3.05; P < 0.05). This is observed either for patients suffering from meningioma or astrocytoma, and this is due to an increase of the wild-type NAT2*4 allelic variant frequency (OR 1.48, 95% CI 0.99-2.19), and a reduction of the commonest defective allelic variant NAT2*5B in the brain tumor patients, compared with healthy subjects (OR 0.54, 95% CI 0.37-0.80).


CONCLUSIONS
This observation indicates that NAT2 could be considered as a low-penetrance gene for brain tumors, and that individuals carrying rapid acetylation alleles are at increased risk of developing brain tumors.
Olivera
M
M
Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
Martínez
C
C
Molina
J A
JA
Alonso-Navarro
H
H
Jiménez-Jiménez
F J
FJ
García-Martín
E
E
Benítez
J
J
Agúndez
J A G
JA
D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001254:Astrocytoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics*; D008579:Meningioma / Q000235:genetics*; D008875:Middle Aged; D019683:Penetrance; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human