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

A. Sebio, D. Páez, J. Salazar, A. Berenguer-Llergo, L. Paré-Brunet, A. Lasa, E. Del Río, M. Tobeña, M. Martín-Richard, M. Baiget, A. Barnadas

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11 Citations (Scopus)

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. © 2014 Macmillan Publishers Limited.
Original languageEnglish
Pages (from-to)256-262
JournalPharmacogenomics Journal
Volume14
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • amphiregulin
  • anti-EGFR
  • colorectal cancer
  • EGFR pathway
  • intergenic
  • polymorphisms

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