Polymorphisms of cytochrome P450 1A2 and N-acetyltransferase genes, meat consumption, and risk of colorectal cancer.
OBJECTIVE
Polymorphic cytochrome P-450 1A2, N-acetyltransferase 1, and 2 are important enzymes involved in the biotransformation of aromatic and heterocyclic amines known as carcinogens for colorectal cancer. A hospital-based study was designed to investigate the association between colorectal cancer and cytochrome P-450 1A2, N-acetyltransferase 1, and N-acetyltransferase 2, with the interaction of meat consumption.


METHODS
We genotyped these polymorphisms for 727 colorectal cancer cases and 736 healthy controls. Information on sociodemographic characteristics and diet were ascertained using a structured questionnaire.


RESULTS
The colorectal cancer risk was significantly increased in rapid N-acetyltransferase 1 carriers with high white meat consumption (almost every day) compared to those carrying the slow N-acetyltransferase 1 genotype with low white meat consumption (less than once a week, odds ratio, 3.00; 95 percent confidence interval, 1.83-4.92). Furthermore, a gene-gene interaction between cytochrome P-450 1A2*1C and N-acetyltransferase 1 was found and modulated by white meat consumption.


CONCLUSIONS
N-acetyltransferase 1 might compete with cytochrome P-450 1A2*1C to increase the colorectal cancer risk in intermediate white meat consumers, whereas the rapid N-acetyltransferase 1 genotype may exert a harmful effect on individuals with high carcinogen exposure.
Yeh
Chih-Ching
CC
Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan.
Sung
Fung-Chang
FC
Tang
Reiping
R
Chang-Chieh
Chung Rong
CR
Hsieh
Ling-Ling
LL
D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D003043:Cocarcinogenesis; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004032:Diet / Q000009:adverse effects*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006571:Heterocyclic Compounds; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008460:Meat / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D006571:Heterocyclic Compounds; D007527:Isoenzymes; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human