Heterocyclic amine intake, smoking, cytochrome P450 1A2 and N-acetylation phenotypes, and risk of colorectal adenoma in a multiethnic population

Objective Heterocyclic amines (HAA) are animal carcinogens that are present in meat cooked at high temperature and in tobacco smoke. These compounds require activation by cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase-2 (NAT2) before they can damage DNA. This study tested the hypotheses that well-done meat and cigarette smoking increase the risk of adenoma, the precursor to most colorectal cancers, especially in individuals with rapid CYP1A2 and rapid NAT2 activities. Design An endoscopy-based case-control study of adenoma was conducted among Caucasians, Japanese and native Hawaiians to test this hypothesis. The overall diet and consumption of well-done meat cooked by various high-temperature methods were assessed by interview in 1016 patients with a first adenoma and 1355 controls with a normal endoscopy. A caffeine test was used to assess CYP1A2 and NAT2 activities in 635 cases and 845 controls. Logistic regression was used to account for matching factors and potential confounders. Results Smoking was associated with an increased risk of adenoma. Weak non-significant elevated OR were observed for the main effects of HAA intakes or NAT2 activity. However, the combined effects of HAA intakes and NAT2 activity were statistically significant. Subjects in both the upper tertiles of NAT2 activity and HAA intake were at increased risk of adenoma compared with subjects in the lower tertiles of NAT2 activity and exposure (2-amino-3,4,8-dimethylimidazo[4,5-f] quinoxaline intake OR 1.70, 95% CI I 1.06 to 2.75; 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline intake OR 1.91, 95% CI 1.16 to 3.16; and 2-amino-1-methyl-6-phenylimidazo[ 4,5-b] pyridine intake OR 2.14, 95% CI 1.31 to 3.49). Conclusion The data suggest that rapid N-acetylators with high HAA intake may be at increased risk of adenoma.