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

Pharmacogenomics. 2020 Sep;21(14):995-1010. doi: 10.2217/pgs-2020-0049. Epub 2020 Sep 8.

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.

Keywords: estrogen; ovarian cancer; pharmacogenetics; platinum therapy; polymorphism; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Disease-Free Survival
  • Female
  • Humans
  • Middle Aged
  • Organoplatinum Compounds / therapeutic use*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Pharmacogenetics / methods
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Progression-Free Survival
  • Young Adult

Substances

  • Organoplatinum Compounds