EGFR ligands and DNA repair genes: Genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer

A. Sebio; J. Salazar; D. Páez; A. Berenguer-Llergo; E. Del Río; M. Tobeña; M. Martín-Richard; I. Sullivan; E. Targarona; J. Balart; M. Baiget; A. Barnadas

doi:10.1038/tpj.2014.33

EGFR ligands and DNA repair genes: Genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer

A. Sebio, J. Salazar, D. Páez, A. Berenguer-Llergo, E. Del Río, M. Tobeña, M. Martín-Richard, I. Sullivan, E. Targarona, J. Balart, M. Baiget, A. Barnadas

Research output: Contribution to journal › Article › Research › peer-review

15 Citations (Scopus)

Abstract

© 2015 Macmillan Publishers Limited. Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.

Original language	English
Pages (from-to)	77-83
Journal	Pharmacogenomics Journal
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/tpj.2014.33
Publication status	Published - 1 Jan 2015

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Sebio, A., Salazar, J., Páez, D., Berenguer-Llergo, A., Del Río, E., Tobeña, M., Martín-Richard, M., Sullivan, I., Targarona, E., Balart, J., Baiget, M., & Barnadas, A. (2015). EGFR ligands and DNA repair genes: Genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer. Pharmacogenomics Journal, 15(1), 77-83. https://doi.org/10.1038/tpj.2014.33

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title = "EGFR ligands and DNA repair genes: Genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer",

abstract = "{\textcopyright} 2015 Macmillan Publishers Limited. Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.",

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Sebio, A, Salazar, J, Páez, D, Berenguer-Llergo, A, Del Río, E, Tobeña, M, Martín-Richard, M, Sullivan, I, Targarona, E, Balart, J, Baiget, M & Barnadas, A 2015, 'EGFR ligands and DNA repair genes: Genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer', Pharmacogenomics Journal, vol. 15, no. 1, pp. 77-83. https://doi.org/10.1038/tpj.2014.33

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T1 - EGFR ligands and DNA repair genes: Genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer

AU - Sebio, A.

AU - Salazar, J.

AU - Páez, D.

AU - Berenguer-Llergo, A.

AU - Del Río, E.

AU - Tobeña, M.

AU - Martín-Richard, M.

AU - Sullivan, I.

AU - Targarona, E.

AU - Balart, J.

AU - Baiget, M.

AU - Barnadas, A.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - © 2015 Macmillan Publishers Limited. Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.

AB - © 2015 Macmillan Publishers Limited. Epidermal growth factor receptor (EGFR) activation by radiation leads to increased cell proliferation and acts as a radioresistance mechanism. Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, and to date, no biomarkers of response have been found. We analyzed polymorphisms in the EGFR and its ligands, DNA repair genes and the thymidylate synthase in 84 stages II and III rectal cancer patients treated with neoadjuvant capecitabine plus radiotherapy. The rs11942466 polymorphism in the amphiregulin (AREG) gene region was associated with a pathological complete response (ypCR) (odds ratio: 0.26; 95% confidence interval: 0.06-0.79; P=0.014). The rs11615 C>T polymorphism in the ERCC1 gene also correlated with the ypCR as no patients with a C/C genotype achieved ypCR; P=0.023. This is the first work to propose variants within the AREG and the ERCC1 genes as promising predictive biomarkers of ypCR in rectal cancer.

U2 - 10.1038/tpj.2014.33

DO - 10.1038/tpj.2014.33

M3 - Article

SN - 1470-269X

VL - 15

SP - 77

EP - 83

JO - Pharmacogenomics Journal

JF - Pharmacogenomics Journal

IS - 1

ER -

EGFR ligands and DNA repair genes: Genomic predictors of complete response after capecitabine-based chemoradiotherapy in locally advanced rectal cancer

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