PMID- 23959273 OWN - NLM STAT- MEDLINE DCOM- 20150105 LR - 20181202 IS - 1473-1150 (Electronic) IS - 1470-269X (Linking) VI - 14 IP - 3 DP - 2014 Jun TI - Intergenic polymorphisms in the amphiregulin gene region as biomarkers in metastatic colorectal cancer patients treated with anti-EGFR plus irinotecan. PG - 256-62 LID - 10.1038/tpj.2013.29 [doi] AB - 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. FAU - Sebio, A AU - Sebio A AD - Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain. FAU - Paez, D AU - Paez D AD - Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain. FAU - Salazar, J AU - Salazar J AD - 1] Department of Genetics, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain [2] U-705 CIBERER, Barcelona, Spain. FAU - Berenguer-Llergo, A AU - Berenguer-Llergo A AD - IDIBELL, Catalan Institute of Oncology, Barcelona, Spain. FAU - Pare-Brunet, L AU - Pare-Brunet L AD - Department of Genetics, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain. FAU - Lasa, A AU - Lasa A AD - Department of Genetics, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain. FAU - Del Rio, E AU - Del Rio E AD - Department of Genetics, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain. FAU - Tobena, M AU - Tobena M AD - Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain. FAU - Martin-Richard, M AU - Martin-Richard M AD - Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain. FAU - Baiget, M AU - Baiget M AD - 1] Department of Genetics, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain [2] U-705 CIBERER, Barcelona, Spain. FAU - Barnadas, A AU - Barnadas A AD - Department of Medical Oncology, Santa Creu i Sant Pau Hospital, Autonoma University of Barcelona, Barcelona, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130820 PL - United States TA - Pharmacogenomics J JT - The pharmacogenomics journal JID - 101083949 RN - 0 (Amphiregulin) RN - 0 (Biomarkers) RN - 0 (DNA Primers) RN - 7673326042 (Irinotecan) RN - EC 2.7.10.1 (ErbB Receptors) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - Amphiregulin/*genetics MH - Base Sequence MH - Biomarkers/*metabolism MH - Camptothecin/*analogs & derivatives/therapeutic use MH - Colorectal Neoplasms/drug therapy/*genetics/pathology MH - DNA Primers MH - ErbB Receptors/*antagonists & inhibitors MH - Female MH - Humans MH - Irinotecan MH - Male MH - Neoplasm Metastasis MH - *Polymorphism, Genetic MH - Polymorphism, Single Nucleotide MH - Real-Time Polymerase Chain Reaction EDAT- 2013/08/21 06:00 MHDA- 2015/01/06 06:00 CRDT- 2013/08/21 06:00 PHST- 2013/03/18 00:00 [received] PHST- 2013/06/20 00:00 [revised] PHST- 2013/07/22 00:00 [accepted] PHST- 2013/08/21 06:00 [entrez] PHST- 2013/08/21 06:00 [pubmed] PHST- 2015/01/06 06:00 [medline] AID - tpj201329 [pii] AID - 10.1038/tpj.2013.29 [doi] PST - ppublish SO - Pharmacogenomics J. 2014 Jun;14(3):256-62. doi: 10.1038/tpj.2013.29. Epub 2013 Aug 20.