title: Polymorphisms in NAT2 and GSTP1 are associated with survival in oral and oropharyngeal cancer.
abstract: BACKGROUND
  Functional polymorphisms in drug metabolizing enzymes (DMEs) may be determinants of survival in oral and oropharyngeal squamous cell carcinoma (OOSCC).
  
  
  METHODS
  OOSCC cases (N=159) with a history of either tobacco or alcohol use were genotyped for polymorphisms in eight DMEs. Overall and disease-specific survival were analyzed using Kaplan-Meier plots and the log-rank test. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) in exploratory analyses of patient subgroups.
  
  
  RESULTS
  Kaplan-Meier analyses showed N-acteyltransferase-2 (NAT2) fast acetylators experienced a 19.7% higher 5-year survival rate than slow acetylators (P=0.03) and this association was similar in oropharyngeal and oral cancer. After multiple adjustment, including tumor site and stage, the NAT2 fast acetylator phenotype was associated with improved overall survival (vs. slow acetylators) provided chemotherapy or radiation were not used (HR, 0.26; 95% CI, 0.10-0.66). However, NAT2 phenotype was unrelated to survival in patients treated with chemoradiotherapy (HR, 1.21; 95% CI, 0.54-2.73) or radiotherapy (HR, 0.67; 95% CI, 0.31-1.59) (P-for-NAT2/treatment-interaction=0.04). Normal activity GSTP1 was associated with a 19.2% reduction in 5-year disease-specific survival relative to reduced activity GSTP1 (P=0.04) but this association was not modified by treatment.
  
  
  CONCLUSIONS
  Our results suggest that functional polymorphisms in NAT2 and GSTP1 are associated with OOSCC survival. Confirmation of these results in larger studies is required.
authors.affiliation: Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15232, USA. jesse.troy@gmail.com
authors.forename: Jesse D
authors.initials: JD
authors.lastname: Troy
authors.forename: Joel L
authors.initials: JL
authors.lastname: Weissfeld
authors.forename: Brenda
authors.initials: B
authors.lastname: Diergaarde
authors.forename: Ada O
authors.initials: AO
authors.lastname: Youk
authors.forename: Shama C
authors.initials: SC
authors.lastname: Buch
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D059248:Chemoradiotherapy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012907:Smoking / Q000453:epidemiology; D015996:Survival Rate
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi