Pharmacogenetic score predicts overall survival, progression-free survival and platinum sensitivity in ovarian cancer

Sara Gagno, Michele Bartoletti, Chiara Romualdi, Elena Poletto, Simona Scalone, Roberto Sorio, Martina Zanchetta, Elena De Mattia, Rossana Roncato, Erika Cecchin, Giorgio Giorda, Giuseppe Toffoli

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: To define the impact of polymorphisms in genes involved in platinum-taxane and estrogen activity in the outcome of platinum-based treated ovarian cancer patients (OCP). Patients & Methods: Two hundred and thirty OCP were analyzed for 124 germ-line polymorphisms to generate a prognostic score for overall survival (OS), progression-free survival (PFS) and platinum-free interval (PFI). Results: ABCG2 rs3219191D>I, UGT1A rs10929302G>A and UGT1A rs2741045T>C polymorphisms were significantly associated with all three parameters (OS, PFS and PFI) and were used to generate a score. Patients in high-risk group had a poorer OS (hazard ratio [HR]: 1.8; 95% CI: 1.3-2.7; p = 0.0019), PFS (HR: 2.0; 95% CI: 1.4-2.9; p < 0.0001) and PFI (HR: 1.9; 95% CI: 1.4-2.8; p = 0.0002) compared with those in low-risk group. Conclusion: The prognostic-score including polymorphisms involved in drug and estrogen pathways stratifies OCP according to OS, PFS and PFI.

Original languageEnglish
Pages (from-to)995-1010
Number of pages16
JournalPharmacogenomics
Volume21
Issue number14
DOIs
Publication statusPublished - Sep 2020

Keywords

  • estrogen
  • ovarian cancer
  • pharmacogenetics
  • platinum therapy
  • polymorphism
  • survival

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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