title: Platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma: glutathione S-transferase genetic polymorphisms as predictive biomarkers of disease outcome.
abstract: BACKGROUND
  The glutathione S-transferases (GSTs) are a group of multifunctional enzymes that catalyze the conjugation of glutathione with a variety of electrophilic compounds, including cytotoxic agents. A significant percentage of normal individuals exhibit genetic polymorphism with a homozygous deletion (null genotype) of the genes, leading to absence of the enzyme.
  
  
  METHODS
  In the present study we analyzed GSTM1 and GSTT1 polymorphisms in the genomic DNA isolated from peripheral blood of patients with ovarian cancer treated with chemotherapy (paclitaxel and cisplatinum) after cytoreductive surgery and assessed its correlation with the clinical outcome of these patients. The median follow-up for the patients was 30 months.
  
  
  RESULTS
  The estimated 3-year survival rate was 59.8% for all patients and 20.8% for carriers of GSTM1-wt/GSTT1-wt (wt indicates wild type) genotype combination (37.7% for GSTM1-wt alone) compared with 83.1% for non-GSTM1-wt/GSTT1-wt genotype carriers (100% for GSTM1-null). The mean survival time was significantly better in patients who are carriers of the GSTM1-null genotype (40.5 vs. 33.5; P=0.006) or carriers of non-GSTM1-wt/ GSTT1-wt genotypes (55.4 vs. 30.7; P=0.009). The progression-free interval was more favorable for GSTM1-null carriers (41.9 vs. 27.4; P=0.024).
  
  
  CONCLUSIONS
  The study suggests that characterization of the drug-metabolizing genetic individual profile can be of great interest in clinical oncology. It can define the optimal chemotherapy for each patient, improve the efficiency, and reduce the incidence of drug toxicity and poor drug responses.
authors.affiliation: Unit of Molecular Oncology, Laboratórios-PISO 4, Instituto Português de Oncologia-Porto, R. Dr. Ant. Bernardino Almeida, 4200-072 Porto, Portugal. ruimmms@mail.com
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.forename: Deolinda
authors.initials: D
authors.lastname: Pereira
authors.forename: Noémia
authors.initials: N
authors.lastname: Afonso
authors.forename: Carlos
authors.initials: C
authors.lastname: Palmeira
authors.forename: Cristina
authors.initials: C
authors.lastname: Faleiro
authors.forename: Carlos
authors.initials: C
authors.lastname: Afonso-Lopes
authors.forename: Margarida
authors.initials: M
authors.lastname: Freitas-Silva
authors.forename: André
authors.initials: A
authors.lastname: Vasconcelos
authors.forename: Sandra
authors.initials: S
authors.lastname: Costa
authors.forename: Teresa
authors.initials: T
authors.lastname: Osório
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001707:Biopsy, Needle; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D005982:Glutathione Transferase; D017239:Paclitaxel; D002945:Cisplatin