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https://ahro.austin.org.au/austinjspui/handle/1/18286| 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 | Date: | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/18286 | DOI: | 10.1038/tpj.2016.56 | ORCID: | 0000-0003-3414-112X | Journal: | The pharmacogenomics journal | PubMed URL: | 27897268 | Type: | Journal Article |
| Appears in Collections: | Journal articles |
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