Single-nucleotide polymorphisms in base excision repair, nucleotide excision repair, and double strand break genes as markers for response to radiotherapy in patients with Stage I to II head-and-neck cancer

Joan Carles, Mariano Monzo, Marta Amat, Sonia Jansa, Rosa Artells, Alfons Navarro, Palmira Foro, Francesc Alameda, Angel Gayete, Bernat Gel, Maribel Miguel, Joan Albanell, Xavier Fabregat

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68 Citations (Scopus)

Abstract

Purpose: Polymorphisms in DNA repair genes can influence response to radiotherapy. We analyzed single-nucleotide polymorphisms (SNP) in nine DNA repair genes in 108 patients with head-and-neck cancer (HNSCC) who had received radiotherapy only. Methods and Materials: From May 1993 to December 2004, patients with Stage I and II histopathologically confirmed HNSCC underwent radiotherapy. DNA was obtained from paraffin-embedded tissue, and SNP analysis was performed using a real-time polymerase chain reaction allelic discrimination TaqMan assay with minor modifications. Results: Patients were 101 men (93.5%) and 7 (6.5%) women, with a median age of 64 years (range, 40 to 89 years). Of the patients, 76 (70.4%) patients were Stage I and 32 (29.6%) were Stage II. The XPF/ERCC1 SNP at codon 259 and XPG/ERCC5 at codon 46 emerged as significant predictors of progression (p = 0.00005 and 0.049, respectively) and survival (p = 0.0089 and 0.0066, respectively). Similarly, when variant alleles of XPF/ERCC1, XPG/ERCC5 and XPA were examined in combination, a greater number of variant alleles was associated with shorter time to progression (p = 0.0003) and survival (p = 0.0002). Conclusions: Genetic polymorphisms in XPF/ERCC1, XPG/ERCC5, and XPA may significantly influence response to radiotherapy; large studies are warranted to confirm their role in HNSCC. © 2006 Elsevier Inc. All rights reserved.
Original languageEnglish
Pages (from-to)1022-1030
JournalInternational Journal of Radiation Oncology Biology Physics
Volume66
DOIs
Publication statusPublished - 15 Nov 2006

Keywords

  • DNA repair
  • Head-and-neck cancer
  • Radiotherapy
  • Single-nucleotide polymorphism

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