Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis

E Morgen; H-J Lenz; D Jonker; D. Tu; G Milano; F Graziano; J Zalcberg; C Karapetis; A Dobrovic; C O'Callaghan; G Liu

doi:10.1038/tpj.2016.56

Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis

E Morgen, H-J Lenz, D Jonker, D. Tu, G Milano, F Graziano, J Zalcberg, C Karapetis, A Dobrovic, C O'Callaghan, G Liu

Research output: Contribution to journal › Review article › peer-review

1 Citation (Scopus)

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.

Original language	English
Pages (from-to)	535-542
Number of pages	8
Journal	PHARMACOGENOMICS JOURNAL
Volume	17
Issue number	6
DOIs	https://doi.org/10.1038/tpj.2016.56
Publication status	Published - 2016

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Morgen, E., Lenz, H-J., Jonker, D., Tu, D., Milano, G., Graziano, F., Zalcberg, J., Karapetis, C., Dobrovic, A., O'Callaghan, C., & Liu, G. (2016). Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis. PHARMACOGENOMICS JOURNAL, 17(6), 535-542. https://doi.org/10.1038/tpj.2016.56

Morgen, E ; Lenz, H-J ; Jonker, D ; Tu, D. ; Milano, G ; Graziano, F ; Zalcberg, J ; Karapetis, C ; Dobrovic, A ; O'Callaghan, C ; Liu, G. / Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis. In: PHARMACOGENOMICS JOURNAL. 2016 ; Vol. 17, No. 6. pp. 535-542.

@article{42e002a59f7a417a86679d609d303ded,

title = "Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis",

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.",

author = "E Morgen and H-J Lenz and D Jonker and D. Tu and G Milano and F Graziano and J Zalcberg and C Karapetis and A Dobrovic and C O'Callaghan and G Liu",

year = "2016",

doi = "10.1038/tpj.2016.56",

language = "English",

volume = "17",

pages = "535--542",

journal = "PHARMACOGENOMICS JOURNAL",

issn = "1470-269X",

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Morgen, E, Lenz, H-J, Jonker, D, Tu, D, Milano, G, Graziano, F, Zalcberg, J, Karapetis, C, Dobrovic, A, O'Callaghan, C & Liu, G 2016, 'Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis', PHARMACOGENOMICS JOURNAL, vol. 17, no. 6, pp. 535-542. https://doi.org/10.1038/tpj.2016.56

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; Lenz, H-J; Jonker, D; Tu, D.; Milano, G; Graziano, F; Zalcberg, J; Karapetis, C; Dobrovic, A; O'Callaghan, C; Liu, G.

In: PHARMACOGENOMICS JOURNAL, Vol. 17, No. 6, 2016, p. 535-542.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - Germline polymorphisms as biomarkers of tumor response in colorectal cancer patients treated with anti-EGFR monoclonal antibodies: a systematic review and meta-analysis

AU - Morgen, E

AU - Lenz, H-J

AU - Jonker, D

AU - Tu, D.

AU - Milano, G

AU - Graziano, F

AU - Zalcberg, J

AU - Karapetis, C

AU - Dobrovic, A

AU - O'Callaghan, C

AU - Liu, G

PY - 2016

Y1 - 2016

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.

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.

U2 - 10.1038/tpj.2016.56

DO - 10.1038/tpj.2016.56

M3 - Review article

VL - 17

SP - 535

EP - 542

JO - PHARMACOGENOMICS JOURNAL

JF - PHARMACOGENOMICS JOURNAL

SN - 1470-269X

IS - 6

ER -