Polymorphisms of cytochrome P450 1A2 and N-acetyltransferase genes, meat consumption, and risk of colorectal cancer.

Abstract

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. 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. 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. 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.