title: A slow acetylator genotype associated with an increased risk of advanced cervical cancer.
abstract: OBJECTIVE
  Human papillomavirus (HPV) is the major etiological agent associated with cervical cancer. However, other risk factors have been indicated, including carcinogen exposure, oral contraceptive usage, certain nutritional deficiencies, and genetic factors. N-acetyltransferase 2 (NAT2) has an important role in the metabolism of several carcinogens. NAT2 polymorphism modulates the activity of the enzyme, by activation, via O-acetylation, or through detoxification, via N-acetylation. This case-control study was designed to evaluate the association between NAT2 polymorphism and genetic susceptibility to cervical cancer.
  
  
  METHODS
  Genomic DNA was obtained from 125 women with advanced cervical cancer and 170 healthy women. PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphisms) was used to analyse two common mutant alleles at NAT2 loci.
  
  
  RESULTS
  The NAT2*6/NAT2*6 genotype, which corresponds to a slow acetylator genotype, was found to be associated with a 3.41-fold (95% CI: 1.35-8.94; P= 0.007) increase in the risk of cervical cancer. For the entire case groups the proportion of cervical cancer cases attributable (attributable proportion) to the NAT2*6/NAT2*6 genotype was 10.2%.
  
  
  CONCLUSIONS
  The results reported in this study suggest that NAT2 polymorphism is a genetic susceptibility factor involved in the carcinogenesis of cervical cancer, and also that the analysis of the allelic profile of populations in different geographic locations may help to understand the incidence of cervical cancer worldwide.
authors.affiliation: Unit of Molecular Oncology, Portuguese Institute of Oncology, Laboratórios - Piso 4, Rua Dr. Bernardino de Almeida, 4200-072 Porto, Portugal. sandracostas@hotmail.com
authors.forename: Sandra
authors.initials: S
authors.lastname: Costa
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.forename: André
authors.initials: A
authors.lastname: Vasconcelos
authors.forename: Daniela
authors.initials: D
authors.lastname: Pinto
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
mesh_terms: D000107:Acetylation; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*
chemical_list: D004273:DNA, Neoplasm; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human