Heterocyclic amines, cytochrome P4501A2, and N-acetyltransferase: issues involved in incorporating putative genetic susceptibility markers into epidemiological studies.
OBJECTIVE
Heterocyclic amines (HCAs), which are found mainly in well-cooked meat, require metabolic activation to function as mutagens and animal carcinogens. Enzymes such as cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) perform this task and are subject to interindividual variation. The source of this variation may be genetic, as in the case of NAT2, or both genetic and environmental as with CYP1A2. The present study examined the effect of HCAs on the NAT2 and CYP1A2 phenotypes in 33 males and 33 females.


METHODS
The subjects consumed a low HCA-containing diet for 1 week followed by a high HCA diet for the subsequent week. The subjects were phenotyped for CYP1A2 and NAT2 at the time of entry into the study (free-living), 1 week later (end of low-HCA or low-induction diet) and 2 weeks later (end of high-HCA or high-induction diet).


RESULTS
Consistent with genetic sources of variability, NAT2 showed little effect of a high-HCA diet and exhibited high intraindividual correlation. CYP1A2, in contrast, was induced by a high-HCA diet and exhibited a more modest intraindividual correlation.


CONCLUSIONS
Incorporating putative genetic susceptibility makers in population studies requires consideration of issues of induction and inhibition of metabolizing enzymes, and effects of covariates.
Sinha
R
R
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20892, USA.
Caporaso
N
N
D000588:Amines / Q000378:metabolism*; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis / Q000235:genetics*; D004032:Diet; D004198:Disease Susceptibility; D004790:Enzyme Induction; D004812:Epidemiologic Methods; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006571:Heterocyclic Compounds / Q000378:metabolism*; D006801:Humans; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D016011:Normal Distribution; D010641:Phenotype; D011110:Polymorphism, Genetic
D000588:Amines; D006571:Heterocyclic Compounds; D009153:Mutagens; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase