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Gut 62:416-422 doi:10.1136/gutjnl-2011-300665
  • Colon
  • Original article

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

  1. Loïc Le Marchand1
  1. 1University of Hawaii Cancer Center, Honolulu, Hawaii, USA
  2. 2Kaiser Permanente Hawaii, Honolulu, Hawaii, USA
  3. 3Pacific Health Research and Education Institute, Honolulu, Hawaii, USA
  1. Correspondence to Dr Loïc Le Marchand, Epidemiology Program, University of Hawaii Cancer Center, 1236 Lauhala Street, Suite 407, Honolulu, HI 96813, USA; loic{at}cc.hawaii.edu
  1. Contributors All authors contributed to either the conception and design, or analysis and interpretation of data, and to drafting the article or revising it critically for important intellectual content. All authors also approved the final version to be published.

  • Revised 18 January 2012
  • Accepted 19 January 2012
  • Published Online First 24 May 2012

Abstract

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.

Footnotes

  • Funding This study was funded by the National Cancer Institute, National Institutes of Health grant R01 CA72520.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was received from the University of Hawaii Committee on Human Studies and the institutional review boards of Kaiser Permanente Hawaii and Hawaii Pacific Health.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Data sharing statement Proposals for collaboration will be considered. Results will also be provided for meta-analyses.

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