Pharmacogenomic assessment of cisplatin-based chemotherapy outcomes in ovarian cancer

Pharmacogenomics. 2014 Feb;15(3):329-37. doi: 10.2217/pgs.13.237.


Aim: 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.

Materials & 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Pharmacological
  • Cisplatin / administration & dosage*
  • Disease-Free Survival
  • Drug-Related Side Effects and Adverse Reactions / genetics
  • Female
  • Genetic Association Studies
  • Humans
  • Inactivation, Metabolic / genetics*
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide


  • Biomarkers, Pharmacological
  • Cisplatin