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

Malmström, Annika ; Łysiak, Malgorzata ; Åkesson, Lisa ; Jakobsen, Ingrid ; Mudaisi, Munila ; Milos, Peter ; Hallbeck, Martin ; Fomichov, Victoria ; Broholm, Helle and Grunnet, Kirsten , et al. (2020) In Pharmacogenomics Journal 20(2). p.213-219
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmacogenomics Journal
volume
20
issue
2
pages
7 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:31624332
  • scopus:85074510229
ISSN
1470-269X
DOI
10.1038/s41397-019-0107-z
language
English
LU publication?
yes
id
2458c2c8-a42c-4cff-9580-fd6d1e50384a
date added to LUP
2019-11-26 14:43:23
date last changed
2024-05-01 00:50:44
@article{2458c2c8-a42c-4cff-9580-fd6d1e50384a,
  abstract     = {{<p>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&gt;A, 1236C&gt;T, 2677G&gt;T/A, and 3435C&gt;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&gt;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&gt;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&gt;T, 2677G&gt;T/A, and 3435C&gt;T of ABCB1. Although the SNV 1199G&gt;A might have some impact, a clinically significant role could not be confirmed.</p>}},
  author       = {{Malmström, Annika and Łysiak, Malgorzata and Åkesson, Lisa and Jakobsen, Ingrid and Mudaisi, Munila and Milos, Peter and Hallbeck, Martin and Fomichov, Victoria and Broholm, Helle and Grunnet, Kirsten and Poulsen, Hans Skovgaard and Bratthäll, Charlotte and Strandeus, Michael and Papagiannopoulou, Angeliki and Stenmark-Askmalm, Marie and Green, Henrik and Söderkvist, Peter}},
  issn         = {{1470-269X}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{213--219}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Pharmacogenomics Journal}},
  title        = {{ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide}},
  url          = {{http://dx.doi.org/10.1038/s41397-019-0107-z}},
  doi          = {{10.1038/s41397-019-0107-z}},
  volume       = {{20}},
  year         = {{2020}},
}