title: Glutathione S-transferase P1 polymorphisms are associated with time to tumor progression in small cell lung cancer patients.
abstract: OBJECTIVE
  Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GSTs). The placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum-based chemotherapy. We investigated whether the polymorphism within the exons 5 and 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients.
  
  
  METHODS
  Ninety-four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala- 114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square test. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves.
  
  
  RESULTS
  We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly shorter TTP (5 vs. 8 months, p = 0.04). Moreover, patients with heterozygote exon 6 variant had presented with extensive-stage disease.
  
  
  CONCLUSIONS
  No individual effect of variant alleles was found in relation to chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome.
authors.affiliation: Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.
authors.forename: R
authors.initials: R
authors.lastname: Saip
authors.forename: F
authors.initials: F
authors.lastname: Sen
authors.forename: B
authors.initials: B
authors.lastname: Vural
authors.forename: E
authors.initials: E
authors.lastname: Ugurel
authors.forename: A
authors.initials: A
authors.lastname: Demirkan
authors.forename: D
authors.initials: D
authors.lastname: Derin
authors.forename: Y
authors.initials: Y
authors.lastname: Eralp
authors.forename: H
authors.initials: H
authors.lastname: Camlica
authors.forename: Z
authors.initials: Z
authors.lastname: Ustuner
authors.forename: U
authors.initials: U
authors.lastname: Ozbek
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D018450:Disease Progression; D005047:Etoposide / Q000008:administration & dosage; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011878:Radiotherapy; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000235:genetics* / Q000628:therapy; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; D005047:Etoposide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D002945:Cisplatin