Association between dietary heterocyclic amine levels, genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 and risk of stomach cancer: a hospital-based case-control study in Japan

Gastric Cancer. 2009;12(4):198-205. doi: 10.1007/s10120-009-0523-x. Epub 2010 Jan 5.


Background: Although the associations between grilled (broiled) or barbecued meats or fish intake and stomach cancer risk have been investigated, the evidence implicating heterocyclic amine (HCA) intake as a cause of stomach cancer is limited. We conducted a case-control study to investigate the association between HCA intake and stomach cancer risk. We also investigated the possible effect of genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on stomach cancer.

Methods: HCA exposure data were assessed using a self-administered food-frequency questionnaire, and estimated HCA intake was verified by measuring 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) values in human hair. A total of 149 cases and 296 controls were included in the analyses. Odds ratios (ORs) were calculated, using conditional logistic regression analysis, to compare intake levels between the first and third tertiles.

Results: Results showed no statistically significant increase in the risk of stomach cancer with respect to total HCA intake (OR, 1.11; 95% confidence interval [CI], 0.36, 3.49), or with respect to the intake of individual HCAs; namely, PhIP, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 did not influence the association of HCA intake with stomach cancer.

Conclusion: In the present study, with a limited sample size of subjects with low HCA exposure, no association was found between HCA intake and stomach cancer, nor was there any evidence of any influence by genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on the risk of stomach cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amines / administration & dosage*
  • Arylamine N-Acetyltransferase / genetics
  • Carcinogens / analysis
  • Case-Control Studies
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A2 / genetics
  • Diet Surveys
  • Female
  • Fish Products
  • Hair / chemistry
  • Heterocyclic Compounds / administration & dosage
  • Humans
  • Imidazoles / analysis
  • Japan / epidemiology
  • Logistic Models
  • Male
  • Meat Products
  • Middle Aged
  • Polymorphism, Genetic*
  • Stomach Neoplasms / epidemiology
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / genetics
  • Young Adult


  • Amines
  • Carcinogens
  • Heterocyclic Compounds
  • Imidazoles
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human