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Title: Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis.
Austin Authors: Morgen, E K;Lenz, H-J;Jonker, D J;Tu, D;Milano, G;Graziano, F;Zalcberg, J;Karapetis, C S;Dobrovic, Alexander ;O'Callaghan, C J;Liu, G
Affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada
Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, Ontario, Canada
USC/Norris Comprehensive Cancer Center, Los Angeles, CA, USA
The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada
Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada
Laboratoire d'Oncopharmacologie EA 3836, Centre Antoine Lacassagne, Nice, France
Division of Medical Oncology, Azienda "Ospedali Riuniti Marche Nord", Pesaro, Italy
Cancer Research Program, School of Public Health and Preventive Medicine, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia
Flinders University and Flinders Medical Centre, Adelaide, South Australia, Australia
Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
Departments of Medicine and Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Issue Date: Dec-2017 2016-11-29
Publication information: The pharmacogenomics journal 2017; 17(6): 535-542
Abstract: Studies of germline polymorphisms as predictors of tumor response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody agents in metastatic colorectal cancer have reported inconsistent results. We performed a systematic review of studies from 1990 to September 2015, followed by random-effects meta-analyses for polymorphisms examined in at least three studies. Of 87 studies, 40 passed the criteria for systematic review and 23 for meta-analysis. The polymorphisms suitable for meta-analysis were CCND1 (rs17852153), COX2 (rs20417), EGF (rs4444903), EGFR (rs712829, rs11543848, 3'UTR CA repeat), FCGR2A (rs1801274), FCGR3A (rs396991), IL8 (rs4073), KRAS (rs61764370) and VEGFA (rs3025039). Meta-analysis yielded nominal significance (at α=0.05) for rs4444903 and rs11543848, but showed no significant results after multiple testing correction; this was unchanged by sensitivity analyses to address subgroups, funnel-plot asymmetries, and study quality. This highlights a tendency for lack of replication in the face of initial positive results, and possibly the unsuitability of relying on tumor response as a surrogate marker in this setting.
DOI: 10.1038/tpj.2016.56
ORCID: 0000-0003-3414-112X
PubMed URL: 27897268
Type: Journal Article
Appears in Collections:Journal articles

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