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

Malmström A, Łysiak M, Åkesson L, Jakobsen I, Mudaisi M, Milos P, Hallbeck M, Fomichov V, Broholm H, Grunnet K, Poulsen HS, Bratthäll C, Strandeus M, Papagiannopoulou A, Stenmark-Askmalm M, Green H, Söderkvist P

Pharmacogenomics J. 20 (2) 213-219 [2020-04-00; online 2019-10-17]

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.

Bioinformatics Compute and Storage [Service]

Clinical Genomics Linköping

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PubMed 31624332

DOI 10.1038/s41397-019-0107-z

Crossref 10.1038/s41397-019-0107-z

pii: 10.1038/s41397-019-0107-z