Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas

Naoko Ishibe, Rashmi Sinha, David W. Hein, Martin Kulldorff, Paul Strickland, Adrian J. Fretland, Wong Ho Chow, Fred F. Kadlubar, Nicholas P. Lang, Nathaniel Rothman

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


High red meat intake has been linked with an increased risk of colorectal cancer and adenomas. During high temperature cooking of red meats, heterocyclic amines (HCAs) are generated; however, to be carcinogenic, they must be metabolized by enzymes including cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 (NAT1) and/or N-acetyltransferase 2 (NAT2). We have conducted a clinic-based case-control study of colorectal adenomas that focused on assessment of exposure to HCAs (estimated by use of a HCA database and meat cooking module) and modification of these exposures by genetic factors. We have previously reported that intake of MelQx was associated with an increased risk of colorectal adenomas [overall association at 80th percentile, > 27.00 ng/day: odds ratio (OR) = 2.68, 95% confidence interval (CI) 1.58-4.55]. Here, we report our evaluation of whether variation in CYP1A2, NAT1 and/or NAT2 modify the association between HCAs and colorectal adenoma formation in 146 cases and 228 frequency-matched controls. The NAT1* 10 allele was associated with a nonsignificant increased risk of colorectal adenomas (OR = 1.43; 95% CI 0.86-2.36). Further, when we analysed 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) intake as a categorical variable, we observed a six-fold increase in adenoma risk among rapid NAT1 acetylators who consumed more than 27 nga day (OR = 6.50; 95% CI 2.16-19.7), whereas among slow NAT1 acetylators, the increase in risk was two-fold (OR = 2.32; 95% CI 1.12-4.81). While suggestive, the results were not significantly different from each other on either an additive or multiplicative scale. In contrast, NAT2 genotype and CYP1A2 and NAT2 hepatic activity measured by caffeine urinary metabolites were not associated with adenoma risk, although an increase in risk with rapid CYP1A2 activity could not be ruled out (OR = 1.46; 95% CI 0.76-2.81). Moreover, there was no evidence that the effect of MelQx was enhanced among subjects in any subgroup defined by variation in these measures. These results are compatible with the hypothesis that high HCA exposure is associated with an increased risk of colorectal adenomas, particularly in genetically susceptible subgroups. Further study of larger populations is needed to confirm and extend these observations.

Original languageEnglish (US)
Pages (from-to)145-150
Number of pages6
Issue number2
StatePublished - 2002
Externally publishedYes


  • Colorectal adenomas
  • Heterocyclic amines
  • MeIQx
  • N-acetyltransferases

ASJC Scopus subject areas

  • Genetics
  • Pharmacology, Toxicology and Pharmaceutics(all)


Dive into the research topics of 'Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas'. Together they form a unique fingerprint.

Cite this