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ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide.
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2019-10-17 , DOI: 10.1038/s41397-019-0107-z
Annika Malmström 1, 2 , Malgorzata Łysiak 2 , Lisa Åkesson 2, 3 , Ingrid Jakobsen 4 , Munila Mudaisi 5 , Peter Milos 6 , Martin Hallbeck 2, 7 , Victoria Fomichov 8 , Helle Broholm 9 , Kirsten Grunnet 10 , Hans Skovgaard Poulsen 10, 11 , Charlotte Bratthäll 12 , Michael Strandeus 13 , Angeliki Papagiannopoulou 2, 7 , Marie Stenmark-Askmalm 14 , Henrik Green 4, 15 , Peter Söderkvist 2
Affiliation  

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.



中文翻译:

胶体母细胞瘤放疗与替莫唑胺联用的患者中ABCB1单核苷酸变异和存活率。

胶质母细胞瘤(GBM)患者的标准治疗方法是使用替莫唑胺(TMZ)进行手术和放射化学疗法(RCT)。TMZ是跨膜药物转运蛋白ABCB1的底物。已经提出,接受TMZ的GBM患者的存活受到ABCB1的不同单核苷酸变体(SNV)的影响。因此,我们检查了ABCB1的SNV:1199G> A,1236C> T,2677G> T / A和3435C> T,并与接受RCT的GBM患者的生存率相关。在一个试验队列(97名患者)中,发现SNV 1199G> A与生存率显着相关,变异型G / G患者的中位OS为18.2个月,而A / G为11.5个月(p = 0.012)。我们发现与其他SNV的生存率无关。然后,我们将该队列扩大到179例患者(扩展队列),还包括一个以SNV 1199G> A为重点的确诊队列(49例患者)。G / G与A / G加A / A的OS中位数分别 为:扩展队列的15.7和11.5个月(p = 0.085),而确认组的OS的中位数OS分别为13.8和16.8个月(p  = 0.19)。总之,在GBM患者接受RCT与TMZ,与生存无相关性被发现为SNV:■1236C> T,2677G> T / A,和3435C>的Ť ABCB1。尽管SNV 1199G> A可能会产生一些影响,但无法确定其临床意义。

更新日期:2020-01-16
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