title: Pharmacogenomic assessment of cisplatin-based chemotherapy outcomes in ovarian cancer.
abstract: OBJECTIVE
  Cisplatin and its analogs are potent antitumor agents. However, their use is restricted by significant variability in tumor response and toxicity. There is a great need to identify genetic markers to predict the most important adverse events and patient outcomes.
  
  
  METHODS
  We have evaluated the association between polymorphisms in 106 genes involved mainly in xenobiotic metabolism, DNA repair, the cell cycle and apoptosis, and outcomes in 104 ovarian cancer patients receiving cisplatin-cyclophosphamide chemotherapy. Arrayed primer extension technology was used to genotype 228 SNPs.
  
  
  RESULTS
  Ten SNPs in nine genes were found to be associated with one or more of the assessed clinical end points. SNPs in TPMT and NQO1 were significantly associated with progression-free survival. Polymorphisms in ERCC5, RAD52, MUTYH and LIG3 correlated with the occurrence of severe neutropenia. SNPs in NAT2 and EPHX1 were associated with anemia and nephrotoxicity, respectively. A SNP in ADH1C was correlated with complete tumor response.
  
  
  CONCLUSIONS
  The results obtained suggest that SNPs in different genes involved in drug metabolism can be important in identifying patients at risk for nonresponse to or toxicity from cisplatin-based treatment.
authors.affiliation: Department of Molecular Bases of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov sq., 2, Moscow, Russia.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Khrunin
authors.forename: Denis V
authors.initials: DV
authors.lastname: Khokhrin
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Moisseev
authors.forename: Vera A
authors.initials: VA
authors.lastname: Gorbunova
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Limborska
mesh_terms: D000328:Adult; D000368:Aged; D054316:Biomarkers, Pharmacological; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D054316:Biomarkers, Pharmacological; D002945:Cisplatin