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Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity

The Pharmacogenomics Journal volume 13, pages 181–188 (2013)Cite this article

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Abstract

The aim of this study was to investigate pharmacogenetic determinants of skin rash associated with epidermal growth factor receptor (EGFR) inhibitor treatment. A total of 109 prospectively sampled cancer patients, receiving the first treatment with an EGFR inhibitor, were genotyped for functional EGFR polymorphisms and tagging variants in genes involved in receptor downstream signaling. Skin rash was absent in 26 (23.9%) patients and associated with shorter overall survival compared with patients presenting skin rash (P=0.005). The EGFR polymorphisms, 497G/A (P=0.008), and the haplotypes of the promoter variants, EGFR–216G/T and –191C/A (P=0.029), were associated with the appearance of skin rash. In addition, a common haplotype in the PIK3CA gene was associated with skin rash (P=0.045) and overall survival (P=0.009). In conclusion, genetic variation within the EGFR gene and its downstream signaling partner PIK3CA might predict EGFR-inhibitor-related skin rash.

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Acknowledgements

This study was financially supported by a research Grant from the Wilhelm Sander Foundation (Grant No 2008.017.1). We would like to thank Professor Dr Konstanze Döhner and Marianne Habdank for technical support in genotyping the EGFR CA repeat. SP is a fellow of the International Graduate School in Molecular Medicine, Ulm.

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Authors and Affiliations

  1. Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Ulm, Germany

    S Parmar, A Seeringer, T Paul & J C Stingl

  2. Department of Internal Medicine II, University of Ulm, Ulm, Germany

    C Schumann & S Rüdiger

  3. Department of Internal Medicine III, Ludwig-Maximilians-University of Munich, Munich, Germany

    S Boeck & V Heinemann

  4. Department of Internal Medicine I, University of Ulm, Ulm, Germany

    V Kächele

  5. Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, Halle, Germany

    T Seufferlein

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Parmar, S., Schumann, C., Rüdiger, S. et al. Pharmacogenetic predictors for EGFR-inhibitor-associated skin toxicity. Pharmacogenomics J 13, 181–188 (2013). https://doi.org/10.1038/tpj.2011.51

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