Polyadenylation polymorphism in the acetyltransferase 1 gene (NAT1) increases risk of colorectal cancer.
Exposure to carcinogens present in the diet, cigarette smoke, or the environment may be associated with increased risk of colorectal cancer.
Aromatic amines (aryl-and heterocyclic) are a class of carcinogens that are important in these exposures.
These compounds can be N-or O-acetylated by the NATI or NAT2 enzymes, resulting in activation or in some cases detoxification.
Recent studies have shown that both NAT2 and NATI genes exhibit variation in human populations and that rapid acetylation by the NAT2 enzyme may be a risk factor for colorectal cancer.
In this study we have analyzed for genetic polymorphism in both NATI and NAT2 in a group of 202 colorectal cancer patients and 112 control subjects from Staffordshire, England.
We find significantly increased risk (odds ratio, 1.9 ; 95% confidence interval, 1.2-3.2 ; P=0.009) associated with the NAT1*10 allele of NAT1, an allele that contains a variant polyadenylation signal.
Individuals with higher stage tumors (Duke's C) were more likely to inherit this variant allele (odds ratio, 2.5 ; 95% confidence interval, 1.3-4.7 ; P=0.005).
This is the first study to test for cancer risk associated with the NATI gene, and these positive findings suggest that NATI alleles may be important genetic determinents of colorectal cancer risk.
Mots-clés Pascal : Tumeur maligne, Côlon, Rectum, Facteur risque, Phénotype acétylateur, Homme, Polymorphisme, Génétique, Epidémiologie moléculaire, Arylamine N-acetyltransferase, Acyltransferases, Transferases, Enzyme, Isozyme, Polyadénylation, Intestin pathologie, Appareil digestif pathologie, Angleterre, Grande Bretagne, Royaume Uni, Europe, Gène NAT1
Mots-clés Pascal anglais : Malignant tumor, Colon, Rectum, Risk factor, Acetylator phenotype, Human, Polymorphism, Genetics, Molecular epidemiology, Arylamine N-acetyltransferase, Acyltransferases, Transferases, Enzyme, Isozyme, Polyadenylation, Intestinal disease, Digestive diseases, England, Great Britain, United Kingdom, Europe
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 95-0485670
Code Inist : 002B13B01. Création : 01/03/1996.