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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Annika Malmström
  • Malgorzata Łysiak
  • Lisa Åkesson
  • Ingrid Jakobsen
  • Munila Mudaisi
  • Peter Milos
  • Martin Hallbeck
  • Victoria Fomichov
  • Helle Broholm
  • Kirsten Grunnet
  • Hans Skovgaard Poulsen
  • Charlotte Bratthäll
  • Michael Strandeus
  • Angeliki Papagiannopoulou
  • Marie Stenmark-Askmalm
  • Henrik Green
  • Peter Söderkvist
Organisations
External organisations
  • Linköping University
  • Region Östergötland
  • Copenhagen University Hospital
  • Kalmar County Hospital
  • Ryhov County Hospital, Jönköping
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
JournalPharmacogenomics Journal
Publication statusE-pub ahead of print - 2019 Oct 17
Publication categoryResearch
Peer-reviewedYes