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ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide
Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Närvårdskliniken.ORCID-id: 0000-0001-8410-4939
Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.ORCID-id: 0000-0002-0244-759X
Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Regionledningskontoret, Regionalt cancercentrum.
Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.ORCID-id: 0000-0003-4450-0333
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2020 (engelsk)Inngår i: The Pharmacogenomics Journal, ISSN 1470-269X, E-ISSN 1473-1150, Vol. 20, nr 2, s. 213-219Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Nature Publishing Group, 2020. Vol. 20, nr 2, s. 213-219
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Identifikatorer
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
Merknad

Funding Agencies|Swedish Cancer SocietySwedish Cancer Society; County Council of ostergotland; South-East Sweden FORSS research grant; LiUCancer

Tilgjengelig fra: 2020-04-14 Laget: 2020-04-14 Sist oppdatert: 2021-12-28bibliografisk kontrollert

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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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