ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomideShow others and affiliations
2020 (English)In: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 20, no 2, p. 213-219Article in journal (Refereed) Published
Abstract [en]
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 1199Gamp;gt;A, 1236Camp;gt;T, 2677Gamp;gt;T/A, and 3435Camp;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 1199Gamp;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 1199Gamp;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 1236Camp;gt;T, 2677Gamp;gt;T/A, and 3435Camp;gt;T of ABCB1. Although the SNV 1199Gamp;gt;A might have some impact, a clinically significant role could not be confirmed.
Place, publisher, year, edition, pages
Nature Publishing Group, 2020. Vol. 20, no 2, p. 213-219
National Category
Clinical Medicine
Identifiers
URN: urn:nbn:se:liu:diva-165049DOI: 10.1038/s41397-019-0107-zISI: 000521728100006PubMedID: 31624332Scopus ID: 2-s2.0-85074510229OAI: oai:DiVA.org:liu-165049DiVA, id: diva2:1423144
Note
Funding Agencies|Swedish Cancer SocietySwedish Cancer Society; County Council of ostergotland; South-East Sweden FORSS research grant; LiUCancer
2020-04-142020-04-142021-12-28Bibliographically approved