ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide

Pharmacogenomics J. 2020 Apr;20(2):213-219. doi: 10.1038/s41397-019-0107-z. Epub 2019 Oct 17.

Abstract

Standard treatment for glioblastoma (GBM) patients is surgery and radiochemotherapy (RCT) with temozolomide (TMZ). TMZ is a substrate for ABCB1, a transmembrane drug transporter. It has been suggested that survival for GBM patients receiving TMZ is influenced by different single-nucleotide variants (SNV) of ABCB1. We therefore examined SNV:s of ABCB1, namely 1199G>A, 1236C>T, 2677G>T/A, and 3435C>T and correlated to survival for GBM patients receiving RCT. In a pilot cohort (97 patients) a significant correlation to survival was found for SNV 1199G>A, with median OS for variant G/G patients being 18.2 months versus 11.5 months for A/G (p = 0.012). We found no correlation to survival for the other SNV:s. We then expanded the cohort to 179 patients (expanded cohort) and also included a confirmatory cohort (49 patients) focusing on SNV 1199G>A. Median OS for G/G versus A/G plus A/A was 15.7 and 11.5 months, respectively (p = 0.085) for the expanded cohort and 13.8 versus 16.8 months (p = 0.19) for the confirmatory. In conclusion, in patients with GBM receiving RCT with TMZ, no correlation with survival was found for the SNV:s 1236C>T, 2677G>T/A, and 3435C>T of ABCB1. Although the SNV 1199G>A might have some impact, a clinically significant role could not be confirmed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Adult
  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy
  • Chemoradiotherapy / methods*
  • Cohort Studies
  • Female
  • Genetic Variation / genetics
  • Glioblastoma / genetics*
  • Glioblastoma / mortality
  • Glioblastoma / therapy
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Polymorphism, Single Nucleotide / genetics*
  • Survival Rate / trends
  • Sweden / epidemiology
  • Temozolomide / administration & dosage*
  • Treatment Outcome

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Antineoplastic Agents, Alkylating
  • Temozolomide