title: Evaluation of glutathione S-transferase polymorphisms and mutagen sensitivity as risk factors for the development of second primary tumors in patients previously diagnosed with early-stage head and neck cancer.
abstract: BACKGROUND
  The objective of this study was to evaluate the effects of polymorphisms in 2 genes in the glutathione S-transferase (GST) family and the mutagen-sensitivity phenotype on the risk of second primary tumors (SPTs) in patients with previously diagnosed early-stage head and neck squamous cell carcinoma. Data were available for 303 patients who were enrolled in a placebo-controlled chemoprevention trial of low-dose 13-cis-retinoic acid to reduce the occurrence of SPTs.
  
  
  METHODS
  A Cox proportional hazards model and survival tree analysis were used to evaluate the association between specified genetic variations and the development of SPTs. The average number of bleomycin-induced chromatid breaks per cell was used to quantify mutagen sensitivity as an individual patient's degree of sensitivity to genotoxicity.
  
  
  RESULTS
  The GST-M1 null genotype was associated with an increased risk for any SPTs (hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.11-3.56) and for tobacco-related SPTs (HR, 2.16; 95% CI, 1.01-4.62) after adjusting for covariates. The GST-T1 null genotype and bleomycin-induced chromatid breaks were not associated with a statistically significant increased risk for SPTs or tobacco-related SPTs after similar adjustment. Simultaneous nonnull status for both GST genotypes was associated with a decreased risk for any SPTs (HR, 0.52; 95% CI, 0.28-0.96) and tobacco-related SPTs (HR, 0.50; 95% CI, 0.22-1.11) compared with null status for GST-M1 accompanied by nonnull status for GST-T1.
  
  
  CONCLUSIONS
  An association was observed between the development of SPTs and the GST-M1 null genotype after successful treatment for early-stage head and neck squamous cell carcinoma. The GST-T1 null genotype and bleomycin-induced chromatid breaks were not associated with an increased risk, and no significant interactions were identified.
authors.affiliation: Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Minard
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Etzel
mesh_terms: D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D001761:Bleomycin / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018890:Chemoprevention / Q000379:methods; D019457:Chromosome Breakage; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors
chemical_list: D001761:Bleomycin; D005982:Glutathione Transferase; D015474:Isotretinoin; D009153:Mutagens; C413545:glutathione S-transferase T1