Polymorphic thymidylate synthase gene impacts on overall survival of patients with epithelial ovarian cancer after platinum-based chemotherapy

Pharmacogenomics. 2012 Nov;13(14):1609-19. doi: 10.2217/pgs.12.136.

Abstract

Aim: High levels of TS have been associated with a worse clinical outcome in several cancers including epithelial ovarian cancer (EOC). The TS gene (TYMS) is highly polymorphic and has an effect on mRNA/protein expression.

Materials & methods: Six TYMS polymorphisms were investigated for overall survival (OS) in 216 EOC patients: TYMS 1494ins/del, TSER (variable number of tandem repeats of 28 bp), TSER G>C, TYMS 1053C>T, TYMS IVS6-68C>T and TYMS 1122A>G.

Results: In a multivariate analysis, TYMS 1494 del/del genotype was associated with a significant increased OS compared with the ins/ins genotype (hazard ratio: 0.36; 95% CI: 0.16-0.82, p = 0.01). Similar results were obtained for the mutant genotypes TYMS 1053TT and TYMS IVS6-68TT. The event-free survival was significantly higher in TYMS 1053TT patients compared with wild-type patients (p = 0.05).

Conclusion: TYMS 1494ins/del, 1053C>T and IVS6-68C>T polymorphisms can be prognostic markers for OS in patients with EOC, independently from stage at diagnosis, median age and tumor histotype.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers, Pharmacological
  • Carcinoma, Ovarian Epithelial
  • Female
  • Follow-Up Studies
  • Genetic Association Studies
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial* / drug therapy
  • Neoplasms, Glandular and Epithelial* / genetics
  • Neoplasms, Glandular and Epithelial* / pathology
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Platinum / administration & dosage*
  • Prognosis
  • Thymidylate Synthase / genetics*

Substances

  • Biomarkers, Pharmacological
  • Platinum
  • Thymidylate Synthase