ERCC2 gene single-nucleotide polymorphism as a prognostic factor for locally advanced head and neck carcinomas after definitive cisplatin-based radiochemotherapy

Maja Guberina, Ali Sak, Christoph Pöttgen, Ingeborg Tinhofer-Keilholz, Volker Budach, Panagiotis Balermpas, Jens Von der Grün, Claus Michael Rödel, Eleni Gkika, Anca Ligia Grosu, Amir Abdollahi, Jürgen Debus, Claus Belka, Steffi Pigorsch, Stephani E. Combs, David Mönnich, Daniel Zips, Chiara De-Colle, Stefan Welz, Annett LingeFabian Lohaus, Gustavo Baretton, Thomas Gauler, Michael Baumann, Mechthild Krause, Martin Schuler, Agnes Bankfalvi, Benedikt Höing, Stephan Lang, Martin Stuschke

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Identifying patients with locally advanced head and neck carcinoma on high risk of recurrence after definitive concurrent radiochemotherapy is of key importance for the selection for consolidation therapy and for individualized treatment intensification. In this multicenter study we analyzed recurrence-associated single-nucleotide polymorphisms (SNPs) in DNA repair genes in tumor DNA from 132 patients with locally advanced head and neck carcinoma (LadHnSCC). Patients were treated with definitive radiotherapy and simultaneous cisplatin-based chemotherapy at six partner sites of the German Cancer Consortium (DKTK) Radiation Oncology Group from 2005 to 2011. For validation, a group of 20 patients was available. Score selection method using proportional hazard analysis and leave-one-out cross-validation were performed to identify markers associated with outcome. The SNPs rs1799793 and rs13181 were associated with survival and the same SNPs and in addition rs17655 with freedom from loco-regional relapse (ffLRR) in the trainings datasets from all patients. The homozygote major rs1799793 genotype at the ERCC2 gene was associated with better (Hazard ratio (HR): 0.418 (0.234–0.744), p = 0.003) and the homozygote minor rs13181 genotype at ERCC2 with worse survival (HR: 2.074, 95% CI (1.177–3.658), p = 0.017) in comparison to the other genotypes. At the ffLRR endpoint, rs1799793 and rs13181 had comparable prognostic value. The rs1799793 and rs13181 genotypes passed the leave-one-out cross-validation procedure and associated with survival and ffLRR in patients with LadHnSCC treated with definitive radiochemotherapy. While findings were confirmed in a small validation dataset, further validation is underway within a prospective biomarker study of the DKTK.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalPharmacogenomics Journal
Volume21
Issue number1
DOIs
StatePublished - Feb 2021
Externally publishedYes

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