Promoter polymorphisms of TOP2A and ERCC1 genes as predictive factors for chemotherapy in non‐small cell lung cancer patients

Autor: Anna Grenda, Justyna Błach, Michał Szczyrek, Paweł Krawczyk, Marcin Nicoś, Barbara Kuźnar Kamińska, Monika Jakimiec, Grażyna Balicka, Izabela Chmielewska, Halina Batura‐Gabryel, Marek Sawicki, Janusz Milanowski
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cancer Medicine, Vol 9, Iss 2, Pp 605-614 (2020)
Druh dokumentu: article
ISSN: 2045-7634
DOI: 10.1002/cam4.2743
Popis: Abstract Background Topoisomerase 2‐alpha (TOP2A) is an enzyme that controls topologic changes in DNA during transcription and replication. ERCC1 is an enzyme that takes part in DNA repair processes. The purpose of this study was to assess the predictive role of particular single nucleotide polymorphisms (SNPs) in the promoter regions of TOP2A and ERCC1 genes in non‐small cell lung cancer patients (NSCLC) treated with chemotherapy. Materials and methods We enrolled 113 NSCLC patients treated in the first line with platinum‐based chemotherapy. Effectiveness was available for 71 patients. DNA was isolated from whole blood using the Qiamp DNA Blood Mini kit (Qiagen). We examined five SNPs: rs11615 (ERCC1), rs3212986 (ERCC1), rs13695 (TOP2A), rs34300454 (TOP2A), rs11540720 (TOP2A). Quantitative PCR using the TaqMan probe (ThermoFisher) was performed on a Eco Illumina Real‐Time PCR system device (Illumina Inc). Results Patients with the A/A genotype in rs11615 of the ERCC1 gene had significantly longer median progression free survival (PFS) (8.5 months; P = .0088). Patients with the C/C genotype in rs3212986 of the ERCC1 gene had longer median PFS (7 months; P = .05). Patients with the C/C genotype in rs34300454 of TOP2A gene had significantly higher median PFS (7.5 months; P = .0029). Carriers of the C/C genotype in rs34300454 of the TOP2A gene had significantly longer median OS (15.5 months; P = .0017). Patients with the A/A genotype in rs11615 of the ERCC1 gene had significantly higher risk of neutropenia (P = .0133). Conclusions Polymorphisms of the TOP2A and ERCC1 genes may be a predictive factor of toxicities and survival for chemotherapy in NSCLC patients.
Databáze: Directory of Open Access Journals
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