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Intergenic polymorphisms in the amphiregulin gene region as biomarkers in metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan

The Pharmacogenomics Journal volume 14, pages 256–262 (2014)Cite this article

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Abstract

In the epidermal growth factor receptor (EGFR) pathway, polymorphisms in EGFR and its ligand EGF have been studied as biomarkers for anti-EGFR treatment. However, the potential pharmacogenetic role of other EGFR ligands such as amphiregulin (AREG) and epiregulin (EREG) has not been elucidated. We studied 74 KRAS and BRAF wild-type metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. Twenty-two genetic variants in EGFR, EGF, AREG and EREG genes were selected using HapMap database and literature resources. Three tagging single-nucleotide polymorphisms in the AREG gene region (rs11942466 C>A, rs13104811 A>G, and rs9996584 C>T) predicted disease control in the multivariate analyses. AREG rs11942466 C>A and rs9996584 C>T were also associated with overall survival (OS). The functional polymorphism, EGFR rs712829 G>T, was associated with progression-free and OS. Our findings support that intergenic polymorphisms in the AREG gene region might help to identify colorectal cancer patients that will benefit from irinotecan plus anti-EGFR therapy.

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Acknowledgements

This work was supported by the Instituto de Salud Carlos III (FIS/1101711, CM11/00102 to Ana Sebio). We thank Carolyn Newey for English language editing.

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Authors and Affiliations

  1. Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain

    A Sebio, D Páez, M Tobeña, M Martín-Richard & A Barnadas

  2. Department of Genetics, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain

    J Salazar, L Paré-Brunet, A Lasa, E del Río & M Baiget

  3. U-705 CIBERER, Barcelona, Spain

    J Salazar & M Baiget

  4. IDIBELL, Catalan Institute of Oncology, Barcelona, Spain

    A Berenguer-Llergo

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  1. A Sebio
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Correspondence to D Páez.

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Sebio, A., Páez, D., Salazar, J. et al. Intergenic polymorphisms in the amphiregulin gene region as biomarkers in metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. Pharmacogenomics J 14, 256–262 (2014). https://doi.org/10.1038/tpj.2013.29

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