TY - JOUR
T1 - Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies
T2 - a systematic review and meta-analysis
AU - Morgen, E. K.
AU - Lenz, H. J.
AU - Jonker, D. J.
AU - Tu, D.
AU - Milano, G.
AU - Graziano, F.
AU - Zalcberg, J.
AU - Karapetis, C. S.
AU - Dobrovic, A.
AU - O’Callaghan, C. J.
AU - Liu, G.
PY - 2017
Y1 - 2017
N2 - 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.The Pharmacogenomics Journal advance online publication, 29 November 2016; doi:10.1038/tpj.2016.56.
AB - 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.The Pharmacogenomics Journal advance online publication, 29 November 2016; doi:10.1038/tpj.2016.56.
UR - http://www.scopus.com/inward/record.url?scp=85000420218&partnerID=8YFLogxK
U2 - 10.1038/tpj.2016.56
DO - 10.1038/tpj.2016.56
M3 - Article
AN - SCOPUS:85000420218
SN - 1470-269X
VL - 17
SP - 535
EP - 542
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
ER -
