Polymorphisms in Xenobiotic Metabolizing Genes, Intakes of Heterocyclic Amines and Red Meat, and Postmenopausal Breast Cancer

Heterocyclic amines (HCAs) are mutagenic compounds generated when meats are cooked at high temperature and for long duration. The findings from previous studies on the relation between HCAs and breast cancer are inconsistent, possibly because of genetic variations in the enzymes metabolizing HCAs. To evaluate whether the associations of intakes of estimated HCAs, meat-derived mutagenicity (MDM), and red meat with risk of postmenopausal breast cancer were modified by N-acetyltransferase 2 (NAT2) acetylator genotype or cytochrome P450 1A2-164 A/C (CYP1A2) polymorphism, we conducted a nested case-control study with 579 cases and 981 controls within a prospective cohort, the Nurses’ Health Study. HCAs and MDM intakes were derived using a cooking method questionnaire administered in 1996. NAT2acetylator genotype, the CYP1A2 polymorphism, and intakes of HCAs, MDM, and red meat were not associated with risk of postmenopausal breast cancer. There was also no interaction between NAT2 acetylator genotype or CYP1A2 polymorphism and HCAs and MDM and red meat intake in relation to breast cancer. These results do not support the hypothesis that genetic polymorphisms of xenobiotic enzymes involved in the metabolism of HCAs may modify the associations between intakes of red meat or meat-related mutagens and breast cancer risk.

[1]  L. Le Marchand,et al.  Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic amines. , 2011, Chemical research in toxicology.

[2]  W. Willett,et al.  Meat Mutagens and Breast Cancer in Postmenopausal Women—A Cohort Analysis , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[3]  T. Illig,et al.  N-acetyltransferase 2, exposure to aromatic and heterocyclic amines, and receptor-defined breast cancer , 2010, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[4]  Jialei Wang,et al.  NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis , 2010, Breast Cancer Research and Treatment.

[5]  Keda Yu,et al.  Lack of association of CYP1A2-164 A/C polymorphism with breast cancer susceptibility: a meta-analysis involving 17,600 subjects , 2010, Breast Cancer Research and Treatment.

[6]  Teruhiko Yoshida,et al.  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 , 2009, Gastric Cancer.

[7]  L. Le Marchand,et al.  Biomonitoring of carcinogenic heterocyclic aromatic amines in hair: a validation study. , 2009, Chemical research in toxicology.

[8]  W. Zheng,et al.  Well-Done Meat Intake, Heterocyclic Amine Exposure, and Cancer Risk , 2009, Nutrition and cancer.

[9]  Teruhiko Yoshida,et al.  Association between dietary heterocyclic amine levels, genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 and risk of colorectal cancer: A hospital-based case-control study in Japan , 2009, Scandinavian journal of gastroenterology.

[10]  W. Willett,et al.  Meat Consumption, Heterocyclic Amines, NAT2, and the Risk of Breast Cancer , 2008, Nutrition and cancer.

[11]  D. Hein,et al.  4-Aminobiphenyl downregulation of NAT2 acetylator genotype-dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in primary mammary epithelial cell cultures from rapid and slow acetylator rats. , 2008, Toxicological sciences : an official journal of the Society of Toxicology.

[12]  Jeffrey S. Morris,et al.  Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer , 2008, Carcinogenesis.

[13]  Yu Shyr,et al.  Meat Intake, Heterocyclic Amine Exposure, and Metabolizing Enzyme Polymorphisms in Relation to Colorectal Polyp Risk , 2008, Cancer Epidemiology Biomarkers & Prevention.

[14]  A. Tjønneland,et al.  Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast cancer in Danish postmenopausal women , 2008, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[15]  R. Elston,et al.  A meta-analysis of the association of N-acetyltransferase 2 gene (NAT2) variants with breast cancer. , 2007, American journal of epidemiology.

[16]  W. Willett,et al.  A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer , 2007, Nature Genetics.

[17]  W. Willett,et al.  Red meat intake and risk of breast cancer among premenopausal women. , 2007, Archives of internal medicine.

[18]  J. Kleinjans,et al.  The CYP1A2-164A-->C polymorphism (CYP1A2*1F) is associated with the risk for colorectal adenomas in humans. , 2005, Cancer letters.

[19]  Federica Gemignani,et al.  A comprehensive analysis of phase I and phase II metabolism gene polymorphisms and risk of colorectal cancer , 2005, Pharmacogenetics and genomics.

[20]  W. Willett,et al.  Prospective study of N‐acetyltransferase‐2 genotypes, meat intake, smoking and risk of colorectal cancer , 2005, International journal of cancer.

[21]  Graham A. Colditz,et al.  The Nurses' Health Study: lifestyle and health among women , 2005, Nature Reviews Cancer.

[22]  C. Qiu,et al.  Steroid hormone receptor expression and proliferation in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. , 2005, Carcinogenesis.

[23]  G. Fakis,et al.  Arylamine N-Acetyltransferases: What We Learn from Genes and Genomes , 2005, Drug metabolism reviews.

[24]  Simak Ali,et al.  The cooked food derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine is a potent oestrogen: a mechanistic basis for its tissue-specific carcinogenicity. , 2004, Carcinogenesis.

[25]  T. Sugimura,et al.  Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish , 2004, Cancer science.

[26]  R. Turesky.  The role of genetic polymorphisms in metabolism of carcinogenic heterocyclic aromatic amines. , 2004, Current drug metabolism.

[27]  Graham A Colditz,et al.  Risk factors for breast cancer according to estrogen and progesterone receptor status. , 2004, Journal of the National Cancer Institute.

[28]  Tomoyuki Shirai,et al.  Detection of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[29]  Rashmi Sinha,et al.  An epidemiologic approach to studying heterocyclic amines. , 2002, Mutation research.

[30]  G. Becher,et al.  Biomarkers of exposure to heterocyclic amines: approaches to improve the exposure assessment. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[31]  R. Sinha,et al.  Excretion of the N(2)-glucuronide conjugate of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine in urine and its relationship to CYP1A2 and NAT2 activity levels in humans. , 2002, Carcinogenesis.

[32]  M. Colvin,et al.  Experimental and simulation studies of heat flow and heterocyclic amine mutagen/carcinogen formation in pan-fried meat patties. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[33]  R Fanelli,et al.  Effect of diet on serum albumin and hemoglobin adducts of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) in humans , 2000, International journal of cancer.

[34]  R. Sinha,et al.  Comparison of heterocyclic amine levels in home-cooked meats with exposure indicators (United States) , 2000, Cancer Causes & Control.

[35]  A. Folsom,et al.  N-Acetyltransferase-2 genetic polymorphism, well-done meat intake, and breast cancer risk among postmenopausal women. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[36]  E White,et al.  Breast cancer, heterocyclic aromatic amines from meat and N-acetyltransferase 2 genotype. , 2000, Carcinogenesis.

[37]  S R Tannenbaum,et al.  N-oxidative metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in humans: excretion of the N2-glucuronide conjugate of 2-hydroxyamino-MeIQx in urine. , 1999, Cancer research.

[38]  S R Tannenbaum,et al.  Biomonitoring of heterocyclic aromatic amine metabolites in human urine. , 1999, Cancer letters.

[39]  K. Turteltaub,et al.  DNA and protein adduct formation in the colon and blood of humans after exposure to a dietary-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[40]  R. Sinha,et al.  Diet, genetic susceptibility and human cancer etiology. , 1999, The Journal of nutrition.

[41]  G. Colditz,et al.  N‐acetyl transferase 2 genotypes, meat intake and breast cancer risk , 1999, International journal of cancer.

[42]  W. Willett,et al.  Predictors of dietary heterocyclic amine intake in three prospective cohorts. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[43]  M. Knize,et al.  Effects of marinating on heterocyclic amine carcinogen formation in grilled chicken. , 1997, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[44]  R. Sinha,et al.  Heterocyclic amine content in fast-food meat products. , 1995, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[45]  F. Dolbeare,et al.  Effect of microwave pretreatment on heterocyclic aromatic amine mutagens/carcinogens in fried beef patties. , 1994, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[46]  R. Minchin,et al.  N-and O-acetylation of aromatic and heterocyclic amine carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS-1 cells. , 1992, Biochemical and biophysical research communications.

[47]  G. Gross,et al.  Quantitation of mutagenic/carcinogenic heterocyclic aromatic amines in food products. , 1992, Journal of chromatography.

[48]  G A Colditz,et al.  Food-based validation of a dietary questionnaire: the effects of week-to-week variation in food consumption. , 1989, International journal of epidemiology.

[49]  H. Ohgaki,et al.  Induction of tumors in the Zymbal gland, oral cavity, colon, skin and mammary gland of F344 rats by a mutagenic compound, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline. , 1989, Carcinogenesis.

[50]  W. Willett,et al.  Reproducibility and validity of a semiquantitative food frequency questionnaire. , 1985, American journal of epidemiology.

[51]  B. Ames,et al.  Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. , 1975, Mutation research.

[52]  R. Sinha,et al.  Meat‐related mutagens/carcinogens in the etiology of colorectal cancer , 2004, Environmental and molecular mutagenesis.

[53]  E. Snyderwine.  Mammary gland carcinogenesis by food‐derived heterocyclic amines: Metabolism and additional factors influencing carcinogenesis by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) , 2002, Environmental and molecular mutagenesis.

[54]  K. Kulp,et al.  Human exposure to heterocyclic amine food mutagens/carcinogens: Relevance to breast cancer , 2002, Environmental and molecular mutagenesis.

[55]  K T Bogen,et al.  Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research. , 1995, Carcinogenesis.