title: NAT1 and NAT2 genetic polymorphisms and environmental exposure as risk factors for oesophageal squamous cell carcinoma: a case-control study.
abstract: BACKGROUND
  Tobacco smoking and red meat consumption are some of the known risk factors associated with the development of oesophageal cancer. N-acetytransferases (NAT1 and NAT2) play a key role in metabolism of carcinogenic arylamines present in tobacco smoke and overcooked red meat. We hypothesized that NAT1 and NAT2 genetic polymorphisms may influence the risk of oesophageal cancer upon exposure to environmental carcinogens.
  
  
  METHODS
  Single nucleotide polymorphisms (SNPs) in the NAT1 and NAT2 genes were investigated by genotyping 732 cases and 768 healthy individuals from two South African populations to deduce the acetylator phenotype (slow, intermediate or rapid) from the combination of the genotyped SNPs.
  
  
  RESULTS
  The 341 CC genotype (rs1801280) was significantly associated with a reduced risk for oesophageal cancer in the Mixed Ancestry population (OR = 0.31; 95% CI 0.11-0.87). The NAT2 slow/intermediate acetylator status significantly increased the risk among cigarette smokers in the Black population (OR = 2.76; 95% CI 1.69-4.52), as well as among alcohol drinkers in the Mixed Ancestry population (OR = 2.77; 95% CI 1.38-5.58). Similarly, the NAT1 slow/intermediate acetylator status was a risk factor for tobacco smokers in the Black population (OR = 3.41; 95% CI 1.95-5.96) and for alcohol drinkers in the Mixed Ancestry population (OR = 3.41; 95% CI 1.70-6.81). In a case-only analysis, frequent red meat consumption was associated with a significantly increased cancer risk for NAT2 slow/intermediate acetylators in the Mixed Ancestry population (OR = 3.55; 95% CI 1.29-9.82; P = 0.019), whereas daily white meat intake was associated with an increased risk among NAT1 slow/intermediate acetylators in the Black population (OR = 1.82; 95% CI 1.09-3.04; P = 0.023).
  
  
  CONCLUSIONS
  Our findings indicate that N-acetylation polymorphisms may modify the association between environmental risk factors and oesophageal cancer risk and that N-acetyltransferases may play a key role in detoxification of carcinogens. Prevention strategies in lifestyle and dietary habits may reduce the incidence of oesophageal cancer in high-risk populations.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Observatory, UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa. MTJMAR002@myuct.ac.za.|Division of Medical Biochemistry and IDM, UCT Faculty of Health Sciences, Cape Town, South Africa. MTJMAR002@myuct.ac.za.
authors.forename: Marco
authors.initials: M
authors.lastname: Matejcic
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Observatory, UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa. matjaz.vogelsang@gmail.com.|Division of Medical Biochemistry and IDM, UCT Faculty of Health Sciences, Cape Town, South Africa. matjaz.vogelsang@gmail.com.
authors.forename: Matjaz
authors.initials: M
authors.lastname: Vogelsang
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Observatory, UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa. y.wang@uct.ac.za.|Division of Medical Biochemistry and IDM, UCT Faculty of Health Sciences, Cape Town, South Africa. y.wang@uct.ac.za.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Observatory, UCT Medical Campus, Anzio Road, Observatory 7925, Cape Town, South Africa. Iqbal.Parker@icgeb.org.|Division of Medical Biochemistry and IDM, UCT Faculty of Health Sciences, Cape Town, South Africa. Iqbal.Parker@icgeb.org.
authors.forename: M
authors.initials: M
authors.lastname: Iqbal Parker
authors.forename: Iqbal M
authors.initials: IM
authors.lastname: Parker
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000208:ethnology* / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D004938:Esophageal Neoplasms / Q000208:ethnology* / Q000209:etiology / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008460:Meat / Q000009:adverse effects; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013019:South Africa / Q000208:ethnology
chemical_list: D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human