Modification by N-acetyltransferase 1 genotype on the association between dietary heterocyclic amines and colon cancer in a multiethnic study.
OBJECTIVE
Colorectal cancer incidence is greater among African Americans, compared to whites in the U.S., and may be due in part to differences in diet, genetic variation at metabolic loci, and/or the joint effect of diet and genetic susceptibility. We examined whether our previously reported associations between meat-derived heterocyclic amine (HCA) intake and colon cancer were modified by N-acetyltransferase 1 (NAT1) or 2 (NAT2) genotypes and whether there were differences by race.


METHODS
In a population-based, case-control study of colon cancer, exposure to HCAs was assessed using a food-frequency questionnaire with a meat-cooking and doneness module, among African Americans (217 cases and 315 controls) and whites (290 cases and 534 controls).


RESULTS
There was no association with NAT1*10 versus NAT1-non*10 genotypes for colon cancer. Among whites, there was a positive association for NAT2-"rapid/intermediate" genotype [odds ratio (OR)=1.4; 95% confidence interval (CI)=1.0, 1.8], compared to the NAT2-"slow" that was not observed among African Americans. Colon cancer associations with HCA intake were modified by NAT1, but not NAT2, regardless of race. However, the "at-risk" NAT1 genotype differed by race. For example, among African Americans, the positive association with 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) was confined to those with NAT1*10 genotype (OR=1.8; 95% CI=1.0, 3.3; P for interaction=0.02, comparing highest to lowest intake), but among whites, an association with 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was confined to those with NAT1-non*10 genotype (OR=1.9; 95% CI=1.1, 3.1; P for interaction=0.03).


CONCLUSIONS
Our data indicate modification by NAT1 for HCA and colon cancer associations, regardless of race. Although the at-risk NAT1 genotype differs by race, the magnitude of the individual HCA-related associations in both race groups are similar. Therefore, our data do not support the hypothesis that NAT1 by HCA interactions contribute to differences in colorectal cancer incidence between African Americans and whites.
Butler
Lesley M
LM
University of California-Davis, Department of Public Health Sciences, Division of Epidemiology, Davis, CA 95616, USA. lmbutler@ucdavis.edu
Millikan
Robert C
RC
Sinha
Rashmi
R
Keku
Temitope O
TO
Winkel
Scott
S
Harlan
Brent
B
Eaton
Allison
A
Gammon
Marilie D
MD
Sandler
Robert S
RS
D001741:Black or African American; D000368:Aged; D000588:Amines; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics*; D004032:Diet; D005787:Gene Frequency; D005838:Genotype; D006571:Heterocyclic Compounds; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008460:Meat; D011110:Polymorphism, Genetic; D044469:Racial Groups
D000588:Amines; D006571:Heterocyclic Compounds; D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human