title: Glutathione S-transferase P1 c.313A > G polymorphism could be useful in the prediction of doxorubicin response in breast cancer patients.
abstract: BACKGROUND
  Identification of predicting factors for anthracyclines-based chemotherapy remains a clinical challenge. Glutathione S-transferase (GSTs) enzymes detoxify chemotherapy drugs and their metabolites. Several polymorphisms in GST genes result in reduced or no activity of the enzymes. Specifically, GSTM1 and GSTT1 genes are polymorphically deleted, the polymorphism GSTP1 c.313A>G (rs1695) determines the amino acid substitution Ile105Val, where the Val-containing enzyme has reduced activity. Also, GSTA1*B allele has reduced levels of GSTA1 enzyme. Several polymorphisms in GSTs have been associated with differences in survival for cancer patients treated with chemotherapy.
  
  
  METHODS
  We genotyped a total of five polymorphisms in GSTM1, GSTT1, GSTP1 and GSTA1 genes in 159 patients with locally advanced breast cancer, treated with single-agent doxorubicin or docetaxel (Taxotere). Gene expression microarrays were performed in 67 breast tumor samples. We correlate this data with treatment outcome.
  
  
  RESULTS
  In multivariate analysis, patients homozygous GG for GSTP1 c.313A>G SNP had a lower risk of chemoresistance when treated with doxorubicin (odds ratio 0.106; confidence interval 0.012-0.898; P=0.040). No association was found in the docetaxel arm. Also, we found that GSTP1 expression varied significantly among breast cancer molecular subtypes.
  
  
  CONCLUSIONS
  GSTP1 may constitute another tool contributing to individualized anthracycline-based therapy.
authors: Medical Oncology Department, Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.
authors: A
authors: A
authors: Romero
authors: M
authors: M
authors: Martín
authors: B
authors: B
authors: Oliva
authors: J
authors: J
authors: de la Torre
authors: V
authors: V
authors: Furio
authors: M
authors: M
authors: de la Hoya
authors: J A
authors: JA
authors: García-Sáenz
authors: A
authors: A
authors: Moreno
authors: J M
authors: JM
authors: Román
authors: E
authors: E
authors: Diaz-Rubio
authors: T
authors: T
authors: Caldés
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D000077143:Docetaxel; D004317:Doxorubicin; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D043823:Taxoids; C413545:glutathione S-transferase T1; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human