Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk.
Foreign compound-metabolizing enzymes may modify the risk of chemically induced cancer.
We wanted to examine enzymes with putative relevance in urinary bladder cancer using molecular genetic analyses of heritably polymorphic enzymes.
Arylamine N-acetyltransferase (NAT2) ; glutathione S-transferases (GSTs) M1 and T1 ; microsomal epoxide hydrolase ; and cytochrome P-450 enzymes (CYP) lAl, 2C19,2D6, and 2E1 were analyzed in 374 cases and in 373 controls in a hospital-based case-control study in Berlin.
Slow acetylation was a significant risk factor in heavy smokers [odds ratio (OR), 2.7 ; 95% confidence interval (Cl), 1.0-7.4], with the greatest risk noted for the allele NAT2*5B.
GSTM1 deficiency was a risk factor independent of smoking and occupation (OR, 1.6 ; CI, 1.2-2.2).
GSTT1 was associated with cancer risk in the nonsmoker subgroup (OR, 2.6 ; CI, 1.1-6.0).
The two amino acid polymorphisms that are known in microsomal epoxide hydrolase were not associated with bladder cancer risk.
CYP2D6 activity was rejected as a risk factor by phenotyping and by detailed molecular genetic analyses.
CYP2C19 may have a role in bladder cancer risk, but polymorphisms in CYP1A1 and 2E1 had no statistically significant impact.
Deficiencies in both NAT2 and GSTMI failed to show significant synergistic or antagonistic interactions. (...)
Mots-clés Pascal : Tumeur maligne, Vessie urinaire, Facteur risque, Glutathione transferase, Transferases, Enzyme, Cytochrome P450, Epoxide hydrolase, Ether hydrolases, Hydrolases, Arylamine N-acetyltransferase, Acyltransferases, Isozyme, Polymorphisme, Prédisposition, Drug-metabolizing enzyme, Pharmacogénétique, Homme, Phénotype, Epidémiologie moléculaire, Allemagne, Europe, Génétique, Vessie pathologie, Appareil urinaire pathologie
Mots-clés Pascal anglais : Malignant tumor, Urinary bladder, Risk factor, Glutathione transferase, Transferases, Enzyme, Cytochrome P450, Epoxide hydrolase, Ether hydrolases, Hydrolases, Arylamine N-acetyltransferase, Acyltransferases, Isozyme, Polymorphism, Predisposition, Drug-metabolizing enzyme, Pharmacogenetics, Human, Phenotype, Molecular epidemiology, Germany, Europe, Genetics, Bladder disease, Urinary system disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0414572
Code Inist : 002B14D02. Création : 10/04/1997.