Oncotarget

Research Papers:

The DNA-polymorphism rs849142 is associated with skin toxicity induced by targeted anti-EGFR therapy using cetuximab

Matthias F. Froelich, Sebastian Stintzing, Jörg Kumbrink, Thomas G.P. Grünewald, Ulrich Mansmann, Volker Heinemann, Thomas Kirchner and Andreas Jung _

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Oncotarget. 2018; 9:30279-30288. https://doi.org/10.18632/oncotarget.25689

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Abstract

Matthias F. Froelich1, Sebastian Stintzing2,3,4, Jörg Kumbrink1,3,4, Thomas G.P. Grünewald1,4,6, Ulrich Mansmann4,5, Volker Heinemann2,3,4, Thomas Kirchner1,3,4 and Andreas Jung1,3,4

1Institute of Pathology, Medical Faculty, LMU Munich, Munich, Germany

2Department of Medicine III, University Hospital LMU Munich, Munich, Germany

3Comprehensive Cancer Center, University Hospital LMU Munich, Munich, Germany

4German Cancer Research Centre (DKFZ); German Cancer consortium (DKTK), Heidelberg, Germany

5Institute for Medical Informatics, Biometry, and Epidemiology, University of Munich, Munich, Germany

6Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology, Medical Faculty, LMU Munich, Munich, Germany

Correspondence to:

Andreas Jung, email: andreas.jung@lmu.de

Keywords: colorectal cancer; SNPs; skin toxicity

Received: December 29, 2017     Accepted: June 12, 2018     Published: July 13, 2018

ABSTRACT

Skin toxicity (ST) is a frequent adverse effect (AE) in anti-epidermal growth factor receptor (EGFR)-targeted treatment of metastatic colorectal cancer (mCRC) resulting in decreased quality of life and problems in clinical management. We wanted to identify biomarkers predicting ST in this setting and focused on 70 DNA polymorphisms associated with acne, the (immunoglobulin fragment crystallizable region) Fcγ-receptor pathway, and systemic lupus erythematosus (SLE) applying next-generation-sequencing (NGS). For the analysis patients with mCRC treated with cetuximab were selected from the FIRE-3 study. A training group consisting of the phenotypes low (1) - and high-grade (3) ST (n = 16) and a validation group (n = 55) representing also the intermediate grade (2) were genotyped and investigated in a genotype-phenotype association analysis. The single nucleotide polymorphism (SNP) rs849142 significantly associated with ST in both the training- (p < 0.01) and validation-group (p = 0.04). rs849142 is located in an intron of the juxtaposed with another zinc finger protein 1 (JAZF1) gene. Haplotype analysis demonstrated significant linkage disequilibrium of rs849142 with JAZF1. Thus, rs849142 might be a predictive biomarker for ST in anti-EGFR treated mCRC patients. Its value in the clinical management of AE has to be validated in larger cohorts.


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