N-acetyltransferase 2, exposure to aromatic and heterocyclic amines, and receptor-defined breast cancer

The role of N-acetyltransferase 2 (NAT2) polymorphism in breast cancer is still unclear. We explored the associations between potential sources of exposure to aromatic and heterocyclic amines (AHA), acetylation status and receptor-defined breast cancer in 1020 incident cases and 1047 population controls of the German GENICA study. Acetylation status was assessed as slow or fast. Therefore, NAT2 haplotypes were estimated using genotype information from six NAT2 polymorphisms. Most probable haplotypes served as alleles for the deduction of NAT2 acetylation status. The risks of developing estrogen receptor &agr; (ER) and progesterone receptor (PR)-positive or negative tumors were estimated for tobacco smoking, consumption of red meat, grilled food, coffee, and tea, as well as expert-rated occupational exposure to AHA with logistic regression conditional on age and adjusted for potential confounders. Joint effects of these factors and NAT2 acetylation status were investigated. Frequent consumption of grilled food and coffee showed higher risks in slow acetylators for receptor-negative tumors [grilled food: ER−: odds ratio (OR) 2.57, 95% confidence interval (CI) 1.07–6.14 for regular vs. rare; coffee: ER−: OR 2.55, 95% CI 1.22–5.33 for ≥4 vs. 0 cups/day]. We observed slightly higher risks for never smokers that are fast acetylators for receptor-positive tumors compared with slow acetylators (ER−: OR 1.32, 95% CI 1.00–1.73). Our results support differing risk patterns for receptor-defined breast cancer. However, the modifying role of NAT2 for receptor-defined breast cancer is difficult to interpret in the light of complex mixtures of exposure to AHA.

[1]  U. Nöthlings,et al.  Identification of a dietary pattern characterized by high-fat food choices associated with increased risk of breast cancer: the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. , 2008, The British journal of nutrition.

[2]  T. Ibiebele,et al.  Dietary pattern predicts breast cancer risk--evidence from the EPIC-Potsdam study. , 2008, The British journal of nutrition.

[3]  T. Illig,et al.  The CYP1B1_1358_GG genotype is associated with estrogen receptor-negative breast cancer , 2008, Breast Cancer Research and Treatment.

[4]  Noel S Weiss,et al.  Subgroup-Specific Associations in the Face of Overall Null Results: Should We Rush In or Fear to Tread? , 2008, Cancer Epidemiology Biomarkers & Prevention.

[5]  A. Gunes,et al.  Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. , 2008, Pharmacogenomics.

[6]  D. Hunter,et al.  Coffee, tea, caffeine and risk of breast cancer: A 22‐year follow‐up , 2008, International journal of cancer.

[7]  C. Ingvar,et al.  Coffee Consumption and CYP1A2*1F Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status , 2008, Cancer Epidemiology Biomarkers & Prevention.

[8]  H. Yatsuya,et al.  Active Smoking, Passive Smoking, and Breast Cancer Risk: Findings from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk , 2008, Journal of epidemiology.

[9]  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.

[10]  J. Chang-Claude,et al.  Cigarette Smoking, N-Acetyltransferase 2 Genotypes, and Breast Cancer Risk: Pooled Analysis and Meta-analysis , 2008, Cancer Epidemiology Biomarkers & Prevention.

[11]  A. Sparks,et al.  The Genomic Landscapes of Human Breast and Colorectal Cancers , 2007, Science.

[12]  Baljit Singh,et al.  Effects of Tobacco Smoke Condensate on Estrogen Receptor-α Gene Expression and Activity , 2007 .

[13]  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.

[14]  Hyon K. Choi,et al.  Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey. , 2007, Arthritis and rheumatism.

[15]  K. Moysich,et al.  Diet and breast cancer , 2007, Cancer.

[16]  A. Neugut,et al.  Cooked Meat and Risk of Breast Cancer—Lifetime Versus Recent Dietary Intake , 2007, Epidemiology.

[17]  B. Karlan,et al.  The CYP1A2 Genotype Modifies the Association Between Coffee Consumption and Breast Cancer Risk Among BRCA1 Mutation Carriers , 2007, Cancer Epidemiology Biomarkers & Prevention.

[18]  C. Holman,et al.  Green tea and the prevention of breast cancer: a case-control study in Southeast China. , 2006, Carcinogenesis.

[19]  H. Brauch,et al.  Expression of xenobiotic and steroid hormone metabolizing enzymes in human breast carcinomas , 2006, International journal of cancer.

[20]  S. Chanock,et al.  Tobacco smoking, NAT2 acetylation genotype and breast cancer risk , 2006, International journal of cancer.

[21]  M. Q. Kemp,et al.  The ligand status of the aromatic hydrocarbon receptor modulates transcriptional activation of BRCA-1 promoter by estrogen. , 2006, Cancer research.

[22]  A. Ascherio,et al.  Estrogen Prevents Neuroprotection by Caffeine in the Mouse 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Model of Parkinson's Disease , 2006, The Journal of Neuroscience.

[23]  T. Illig,et al.  Variation of the N-Acetyltransferase 2 Gene in a Romanian and a Kyrgyz Population , 2006, Cancer Epidemiology Biomarkers & Prevention.

[24]  Ulrike Peters,et al.  Is It Time to Abandon the Food Frequency Questionnaire? , 2005, Cancer Epidemiology Biomarkers & Prevention.

[25]  G. Windham,et al.  Cigarette Smoking and Effects on Hormone Function in Premenopausal Women , 2005, Environmental health perspectives.

[26]  Pierre Darlu,et al.  Inferring haplotypes at the NAT2 locus: the computational approach , 2005, BMC Genetics.

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

[28]  Thomas Brüning,et al.  ERCC2 genotypes and a corresponding haplotype are linked with breast cancer risk in a German population. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[29]  M. García-Closas,et al.  Etiology of hormone receptor-defined breast cancer: a systematic review of the literature. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[30]  A. Ziogas,et al.  Active smoking, household passive smoking, and breast cancer: evidence from the California Teachers Study. , 2004, Journal of the National Cancer Institute.

[31]  M. Denison,et al.  Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. , 2003, Annual review of pharmacology and toxicology.

[32]  Peter Donnelly,et al.  A comparison of bayesian methods for haplotype reconstruction from population genotype data. , 2003, American journal of human genetics.

[33]  Stephen S. Hecht,et al.  Tobacco carcinogens, their biomarkers and tobacco-induced cancer , 2003, Nature Reviews Cancer.

[34]  Thomas E Rohan,et al.  Cigarette smoking and the risk of breast cancer in women: a review of the literature. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[35]  P. Donnelly,et al.  A new statistical method for haplotype reconstruction from population data. , 2001, American journal of human genetics.

[36]  K. Anderson,et al.  Distribution and concordance of N-acetyltransferase genotype and phenotype in an American population. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[37]  T. J. Doyle,et al.  Tea consumption and cancer incidence in a prospective cohort study of postmenopausal women. , 1996, American journal of epidemiology.

[38]  E. Negri,et al.  Cigarette smoking and the risk of breast cancer , 1996, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[39]  R. Goldbohm,et al.  Consumption of black tea and cancer risk: a prospective cohort study. , 1996, Journal of the National Cancer Institute.

[40]  Z. Y. Wang,et al.  Tea and cancer. , 1993, Journal of the National Cancer Institute.

[41]  D. Grant Molecular genetics of the N-acetyltransferases. , 1993, Pharmacogenetics.

[42]  R. Hayes,et al.  Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. , 1992, Pharmacogenetics.

[43]  C. la Vecchia,et al.  The antiestrogenic effect of cigarette smoking in women. , 1990, American journal of obstetrics and gynecology.

[44]  Baljit Singh,et al.  Effects of tobacco smoke condensate on estrogen receptor-alpha gene expression and activity. , 2007, Endocrinology.

[45]  K. Ickstadt,et al.  Breast cancer: a candidate gene approach across the estrogen metabolic pathway , 2007, Breast Cancer Research and Treatment.

[46]  Jan Lubinski,et al.  Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers , 2006, International journal of cancer.

[47]  H. Brauch,et al.  Factors Modifying the Association Between Hormone-Replacement Therapy and Breast Cancer Risk , 2005, European Journal of Epidemiology.

[48]  Alicja Wolk,et al.  Coffee, tea, and caffeine consumption and breast cancer incidence in a cohort of Swedish women. , 2002, Annals of epidemiology.

[49]  M. Doll,et al.  Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[50]  A. Bergen,et al.  Cigarette smoking. , 1999, Journal of the National Cancer Institute.