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Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis.
Morgen, E K; Lenz, H-J; Jonker, D J; Tu, D; Milano, G; Graziano, F; Zalcberg, J; Karapetis, C S; Dobrovic, A; O'Callaghan, C J; Liu, G.
Afiliación
  • Morgen EK; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
  • Lenz HJ; Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, Ontario, Canada.
  • Jonker DJ; USC/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Tu D; The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
  • Milano G; Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada.
  • Graziano F; Laboratoire d'Oncopharmacologie EA 3836, Centre Antoine Lacassagne, Nice, France.
  • Zalcberg J; Division of Medical Oncology, Azienda "Ospedali Riuniti Marche Nord", Pesaro, Italy.
  • Karapetis CS; Cancer Research Program, School of Public Health and Preventive Medicine, Faculty of Medicine, Monash University, Melbourne, Victoria, Australia.
  • Dobrovic A; Flinders University and Flinders Medical Centre, Adelaide, South Australia, Australia.
  • O'Callaghan CJ; Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia.
  • Liu G; School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia.
Pharmacogenomics J ; 17(6): 535-542, 2017 12.
Article en En | MEDLINE | ID: mdl-27897268
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Neoplasias Colorrectales / Receptores ErbB / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Neoplasias Colorrectales / Receptores ErbB / Anticuerpos Monoclonales Tipo de estudio: Prognostic_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Pharmacogenomics J Asunto de la revista: BIOLOGIA MOLECULAR / FARMACOLOGIA Año: 2017 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos