title: Glutathione-S-transferase (GST) polymorphisms are associated with relapse after radical prostatectomy.
abstract: BACKGROUND
  Organ confined prostate cancer (PCa) can be cured by radical retropubic prostatectomy (RRP); however, some tumors will still recur. Current tools fail to identify patients at risk of recurrence. Glutathione-S-transferases (GSTs) are involved in the metabolism of carcinogens, hormones and drugs. Thus, genetic polymorphisms that modify the GST activities may modify the risk of PCa recurrence.
  
  
  METHODS
  We retrospectively recruited Argentine PCa patients treated with RRP to study the association between GST polymorphisms and PCa biochemical relapse after RRP. We genotyped germline DNA in 105 patients for: GSTP1 c.313A>G (p.105 Ile>Val, rs1695) by PCR-RFLP; and GSTT1 null and GSTM1 null polymorphisms by multiplex PCR. Kaplan-Meier curves and Cox proportional hazard models were used to evaluate these associations.
  
  
  RESULTS
  Patients with GSTP1 c.313GG genotype showed shorter biochemical relapse-free survival (BRFS) (P = 0.003) and higher risk for recurrence in unadjusted (Hazard ratio (HR) = 3.16, 95% confidence interval (95% CI) = 1.41-7.06, P = 0.005) and multivariate models (HR = 3.01, 95% CI = 1.13-8.02, P = 0.028). We did not find significant associations for GSTT1 and GSTM1 genotypes. In addition, we found shorter BRFS (P = 0.010) and increased risk for recurrence for patients having two or more risk alleles when we combined the genotypes of the three GSTs in multivariate models (HR = 3.06, 95% CI = 1.20-7.80, P = 0.019).
  
  
  CONCLUSIONS
  Our results give support to the implementation of GSTs genotyping for personalized therapies as a novel alternative for PCa management for patients who undergo RRP. To the best of our knowledge, this is the first study that examined GST polymorphisms in PCa progression in Argentine men. Replication of our findings in larger cohort is warranted.
authors.affiliation: Department of Biological Chemistry, School of Sciences, University of Buenos Aires-IQUIBICEN, CONICET, Buenos Aires, Argentina. jcotignola@qb.fcen.uba.ar
authors.forename: J
authors.initials: J
authors.lastname: Cotignola
authors.forename: D B
authors.initials: DB
authors.lastname: Leonardi
authors.forename: A
authors.initials: A
authors.lastname: Shahabi
authors.forename: A D
authors.initials: AD
authors.lastname: Acuña
authors.forename: M C
authors.initials: MC
authors.lastname: Stern
authors.forename: N
authors.initials: N
authors.lastname: Navone
authors.forename: C
authors.initials: C
authors.lastname: Scorticati
authors.forename: A
authors.initials: A
authors.lastname: De Siervi
authors.forename: O
authors.initials: O
authors.lastname: Mazza
authors.forename: E
authors.initials: E
authors.lastname: Vazquez
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D012307:Risk Factors
chemical_list: D005982:Glutathione Transferase