title: Intergenic polymorphisms in the amphiregulin gene region as biomarkers in metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan.
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.
authors: Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors: A
authors: A
authors: Sebio
authors: Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors: D
authors: D
authors: Páez
authors: 1] Department of Genetics, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain [2] U-705 CIBERER, Barcelona, Spain.
authors: J
authors: J
authors: Salazar
authors: IDIBELL, Catalan Institute of Oncology, Barcelona, Spain.
authors: A
authors: A
authors: Berenguer-Llergo
authors: Department of Genetics, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors: L
authors: L
authors: Paré-Brunet
authors: Department of Genetics, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors: A
authors: A
authors: Lasa
authors: Department of Genetics, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors: E
authors: E
authors: Del Río
authors: Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors: M
authors: M
authors: Tobeña
authors: Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors: M
authors: M
authors: Martín-Richard
authors: 1] Department of Genetics, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain [2] U-705 CIBERER, Barcelona, Spain.
authors: M
authors: M
authors: Baiget
authors: Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autònoma University of Barcelona, Barcelona, Spain.
authors: A
authors: A
authors: Barnadas
mesh_terms: D066258:Amphiregulin / Q000235:genetics*; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009362:Neoplasm Metastasis; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D066258:Amphiregulin; D015415:Biomarkers; D017931:DNA Primers; D000077146:Irinotecan; D066246:ErbB Receptors; D002166:Camptothecin