title: Molecular prognosticators and genomic instability in papillary thyroid cancer.
abstract: OBJECTIVE
  Tumor progression has been attributed to the accumulation of DNA damage concurrent with selection of advantageous mutations; this DNA damage may result from failure to maintain genomic integrity or from susceptibility to carcinogens. Glutathione S-transferases (GSTs), enzymes that metabolize many carcinogens, may play a role in preserving genome integrity. The objectives of this study are to assess the relationship of GST genotypes with prognosis, clinicopathologic parameters, and genomic instability in papillary thyroid cancer.
  
  
  METHODS
  Prospective analysis.
  
  
  METHODS
  GSTM1 and GSTT1 genotypes of 35 matched normal and papillary thyroid cancer specimens were determined by polymerase chain reaction (PCR) using primers specific for the coding sequences of each gene. Genomic instability was measured by intersimple sequence repeat PCR for each tumor/normal pair and compared with the GAMES prognostic scoring system and clinicopathologic parameters including age, extrathyroidal extension, tumor grade, size, stage metastasis, sex, and smoking history.
  
  
  RESULTS
  GSTM1 and GSTT1 null genotypes were found in the normal tissues of 46% and 45%, respectively. No gene losses were detected in the tumor specimens. A significant association between the GSTM1 null genotype and increased risk of recurrence and death was observed. Elevated GII correlated with smoking and tumor stage but not with GST genotype.
  
  
  CONCLUSIONS
  The association of GSTM1 null genotype with intermediate and high risk GAMES categories suggests that GSTM1 provides some protection against disease progression. However, this protection does not confer resistance to disease onset. GST genotyping may be a useful adjunct prognosticator with GAMES.
authors.affiliation: Department of Head and Neck Surgery, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, U.S.A. nestor.rigual@roswellpark.org
authors.forename: Nestor R
authors.initials: NR
authors.lastname: Rigual
authors.forename: Garth R
authors.initials: GR
authors.lastname: Anderson
authors.forename: Thom R
authors.initials: TR
authors.lastname: Loree
authors.forename: Sam
authors.initials: S
authors.lastname: Wiseman
authors.forename: Sadir
authors.initials: S
authors.lastname: Alrawi
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Stoler
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D004273:DNA, Neoplasm / Q000032:analysis; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D005982:Glutathione Transferase