Association of Glutathione S-Transferase P-1 (GSTP-1) rs1695 polymorphism with overall survival in glioblastoma patients treated with combined radio-chemotherapy

Invest New Drugs. 2018 Apr;36(2):340-345. doi: 10.1007/s10637-017-0516-2. Epub 2017 Sep 30.

Abstract

Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m2 during RT and 200 mg/m2 days 1 → 5 every 28 days) were enrolled. Survival curves were calculated using the Kaplan-Meier method, and the log-rank test was used to evaluate differences between curves. A trend to a statistically significant association with PFS in univariate and multivariate COX regression analysis was found with GSTP-1 rs1695 polymorphism (p = 0.087 and p = 0.097 on univariate and multivariate analyses, respectively). Conversely, the same GSTP-1 rs1695 SNP revealed a statistically significant association with OS (p = 0.007 and p = 0.042 on univariate and multivariate analysis, respectively). Our pharmacogenetic prospective study suggests that GSTP-1 rs1695 genotypes can be associated with different OS in GBM patients treated with RT and TMZ.

Keywords: Chemotherapy; GSTP-1; Glioblastoma; Radiotherapy; Single nucleotide polymorphism; rs1695.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemoradiotherapy*
  • Disease-Free Survival
  • Female
  • Genetic Association Studies*
  • Glioblastoma / enzymology
  • Glioblastoma / genetics*
  • Glioblastoma / therapy*
  • Glutathione S-Transferase pi / genetics*
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide / genetics*
  • Survival Analysis

Substances

  • GSTP1 protein, human
  • Glutathione S-Transferase pi