title: Impact of CYP1A1, GSTM1, and GSTT1 polymorphisms in overall and specific prostate cancer survival.
abstract: OBJECTIVE
  Prognostic biomarkers that distinguish between patients with good or poor outcome can be used to guide decisions of whom to treat and how aggressively. In this sense, several groups have proposed genetic polymorphisms as potential susceptibility and prognostic biomarkers; however, their validity has not been proven. Thus, the main goal of the present work was to investigate the potential role of single and combined CYP1A1, GSTM1, and GSTT1 genotypes as modifiers of cancer survival in Chilean patients with prostate cancer.
  
  
  METHODS
  A total of 260 histologically confirmed patients were recruited from a voluntary screening, and genomic DNA was obtained from their blood samples for genotyping analyses to detect the CYP1A1*2A polymorphism and GSTM1 and GSTT1 deletions. The progression of illness and mortality were estimated with a median follow-up of 8.82 years. Adjusted estimated genotype risks were evaluated by hazard ratio and 95% CI using the Cox proportional model. In addition, the Kaplan-Meier survival method and log-rank test were used to evaluate patient survival with regard to genotype.
  
  
  RESULTS
  The 9-year overall and specific survival rates were 67.6% and 36.6% in the GSTT1null group, 67.6% and 58.7% in the GSTM1non-null group, 69.0% and 51.6% in the *1A/*2A group, 63.9% and 61.5% in the *2A/*2A group vs. 76.2% and 62.3% in the GSTT1non-null group, 82.3% and 50% in the GSTM1null group, and 83.7% and 56.3% in the *1A/*1A group, respectively. The hazard ratios and the Kaplan-Meier curve results demonstrate that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes are significantly associated with mortality. Our study has two main limitations: a relatively small sample size and a low global mortality percentage (25.4%); thus, we need to continue the follow-up to confirm these findings.
  
  
  CONCLUSIONS
  Our results suggest that the GSTM1non-null, GSTT1null, and CYP1A1*2A genotypes may be good prognosis markers, particularly in patients with high-risk tumors.
authors: Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Center of Pharmacological and Toxicological Research (IFT), ICBM, Program of Molecular and Clinical Pharmacology, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Urology, University of Chile Clinical Hospital (HCUCH), Santiago, Chile; National Cancer Corporation (CONAC), Santiago, Chile.
authors: Cristián A
authors: CA
authors: Acevedo
authors: Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Center of Pharmacological and Toxicological Research (IFT), ICBM, Program of Molecular and Clinical Pharmacology, Faculty of Medicine, University of Chile, Santiago, Chile. Electronic address: lquinone@med.uchile.cl.
authors: Luis A
authors: LA
authors: Quiñones
authors: Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Center of Pharmacological and Toxicological Research (IFT), ICBM, Program of Molecular and Clinical Pharmacology, Faculty of Medicine, University of Chile, Santiago, Chile.
authors: Johanna
authors: J
authors: Catalán
authors: Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Center of Pharmacological and Toxicological Research (IFT), ICBM, Program of Molecular and Clinical Pharmacology, Faculty of Medicine, University of Chile, Santiago, Chile; Environmental Health Program, School of Public Health, Faculty of Medicine, University of Chile, Santiago, Chile.
authors: Dante D
authors: DD
authors: Cáceres
authors: National Cancer Corporation (CONAC), Santiago, Chile.
authors: Juan A
authors: JA
authors: Fullá
authors: Laboratory of Chemical Carcinogenesis and Pharmacogenetics, Center of Pharmacological and Toxicological Research (IFT), ICBM, Program of Molecular and Clinical Pharmacology, Faculty of Medicine, University of Chile, Santiago, Chile; Department of Processes Management and Care, SSMOC, Santiago, Chile.
authors: Angela M
authors: AM
authors: Roco
mesh_terms: D000368:Aged; D002677:Chile; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; 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; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C569463:CYP1A1 protein, human; C413545:glutathione S-transferase T1
keywords: Biomarkers; CYP; GST; Polymorphisms; Prostate cancer; Survival