Meat and heterocyclic amine intake, smoking, NAT1 and NAT2 polymorphisms, and colorectal cancer risk in the multiethnic cohort study.
BACKGROUND
N-acetyltransferases (NAT) 1 and 2 are polymorphic enzymes catalyzing the metabolic activation of heterocyclic amines. We investigated the modifying effects of NAT1 and NAT2 polymorphisms on the association of meat consumption, heterocyclic amine intake, and smoking with colorectal cancer risk.


METHODS
In the Multiethnic Cohort study, participants completed a smoking history and a food-frequency questionnaire at recruitment and a cooked meat module 5 years later to estimate heterocyclic amine intake (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline). Blood samples were collected from incident cases and age-, sex-, ethnicity-, frequency-matched controls to determine genotypes. For analysis of meat intake and smoking, data were available for 1,009 cases and 1,522 controls; for heterocyclic amine intake analyses, 398 cases and 1,444 controls were available. Multivariate logistic regression models were used to estimate odds ratios.


RESULTS
Smoking was associated with an increased colorectal cancer risk (odds ratio, 1.51; 95% confidence interval, 1.17-1.95) for > or =30 pack-years compared with never smokers (P trend = 0.0004). The association was stronger with presence of the "rapid" compared with the "slow/intermediate" NAT2 genotype (P interaction = 0.003). No significant associations were observed for intakes of red meat, processed meat, and heterocyclic amine, or meat doneness preference, but a dietary pattern high in meat showed a weak positive interaction with the NAT2 genotype (P interaction = 0.05).


CONCLUSIONS
The enhanced association between smoking and colorectal cancer risk in subjects with the NAT2 rapid genotype supports a role for NAT2 and tobacco smoke heterocyclic amines in the etiology of colorectal cancer. This study only provides weak support for a similar association with meat heterocyclic amines.
Nöthlings
Ute
U
Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA.
Yamamoto
Jennifer F
JF
Wilkens
Lynne R
LR
Murphy
Suzanne P
SP
Park
Song-Yi
SY
Henderson
Brian E
BE
Kolonel
Laurence N
LN
Le Marchand
Loïc
L
D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics; D004032:Diet; D005260:Female; D006254:Hawaii / Q000453:epidemiology; D006571:Heterocyclic Compounds / Q000009:adverse effects / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D016015:Logistic Models; D015141:Los Angeles / Q000453:epidemiology; D008297:Male; D008460:Meat; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D011795:Surveys and Questionnaires
D006571:Heterocyclic Compounds; D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human