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ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Närvårdskliniken.ORCID iD: 0000-0001-8410-4939
Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0002-0244-759X
Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Regional Cancer Center.
Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0003-4450-0333
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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
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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

Available from: 2020-04-14 Created: 2020-04-14 Last updated: 2021-12-28Bibliographically approved

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Malmström, AnnikaJakobsen Falk, IngridMudaisi, Munila

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Malmström, AnnikaLysiak, MalgorzataÅkesson, LisaJakobsen Falk, IngridMudaisi, MunilaMilos, PeterHallbeck, MartinFomichov Casaballe, VictoriaPapagiannopoulou, AngelikiGreen, HenrikSöderkvist, Peter
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Division of Cell BiologyFaculty of Medicine and Health SciencesNärvårdsklinikenDepartment of Biomedical and Clinical SciencesRegional Cancer CenterDivision of Drug ResearchDivision of Surgery, Orthopedics and OncologyDepartment of OncologyDivision of NeurobiologyDepartment of NeurosurgeryClinical pathologyDepartment of Medical and Health SciencesEnheten för folkhälsa
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