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Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer
Adverse reactions to capecitabine-based chemotherapy limit full administration of cytotoxic agents. Likewise, genetic variations associated with capecitabine-related adverse reactions are associated with controversial results and a low predictive value. Thus, more evidence on the role of these varia...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467446/ https://www.ncbi.nlm.nih.gov/pubmed/25691056 |
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author | García-González, Xandra Cortejoso, Lucía García, María I. García-Alfonso, Pilar Robles, Luis Grávalos, Cristina González-Haba, Eva Marta, Pellicer Sanjurjo, María López-Fernández, Luis A. |
author_facet | García-González, Xandra Cortejoso, Lucía García, María I. García-Alfonso, Pilar Robles, Luis Grávalos, Cristina González-Haba, Eva Marta, Pellicer Sanjurjo, María López-Fernández, Luis A. |
author_sort | García-González, Xandra |
collection | PubMed |
description | Adverse reactions to capecitabine-based chemotherapy limit full administration of cytotoxic agents. Likewise, genetic variations associated with capecitabine-related adverse reactions are associated with controversial results and a low predictive value. Thus, more evidence on the role of these variations is needed. We evaluated the association between nine polymorphisms in MTHFR, CDA, TYMS, ABCB1, and ENOSF1 and adverse reactions, dose reductions, treatment delays, and overall toxicity in 239 colorectal cancer patients treated with capecitabine-based regimens. The ABCB1*1 haplotype was associated with a high risk of delay in administration or reduction in the dose of capecitabine, diarrhea, and overall toxicity. CDA rs2072671 A was associated with a high risk of overall toxicity. TYMS rs45445694 was associated with a high risk of delay in administration or reduction in the dose of capecitabine, HFS >1 and HFS >2. Finally, ENOSF1 rs2612091 was associated with HFS >1, but was a poorer predictor than TYMS rs45445694. A score based on ABCB1-CDA polymorphisms efficiently predicts patients at high risk of severe overall toxicity (PPV, 54%; sensitivity, 43%) in colorectal cancer patients treated with regimens containing capecitabine. Polymorphisms in ABCB1, CDA, ENOSF1,and TYMS could help to predict specific and overall severe adverse reactions to capecitabine. |
format | Online Article Text |
id | pubmed-4467446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44674462015-06-22 Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer García-González, Xandra Cortejoso, Lucía García, María I. García-Alfonso, Pilar Robles, Luis Grávalos, Cristina González-Haba, Eva Marta, Pellicer Sanjurjo, María López-Fernández, Luis A. Oncotarget Clinical Research Paper Adverse reactions to capecitabine-based chemotherapy limit full administration of cytotoxic agents. Likewise, genetic variations associated with capecitabine-related adverse reactions are associated with controversial results and a low predictive value. Thus, more evidence on the role of these variations is needed. We evaluated the association between nine polymorphisms in MTHFR, CDA, TYMS, ABCB1, and ENOSF1 and adverse reactions, dose reductions, treatment delays, and overall toxicity in 239 colorectal cancer patients treated with capecitabine-based regimens. The ABCB1*1 haplotype was associated with a high risk of delay in administration or reduction in the dose of capecitabine, diarrhea, and overall toxicity. CDA rs2072671 A was associated with a high risk of overall toxicity. TYMS rs45445694 was associated with a high risk of delay in administration or reduction in the dose of capecitabine, HFS >1 and HFS >2. Finally, ENOSF1 rs2612091 was associated with HFS >1, but was a poorer predictor than TYMS rs45445694. A score based on ABCB1-CDA polymorphisms efficiently predicts patients at high risk of severe overall toxicity (PPV, 54%; sensitivity, 43%) in colorectal cancer patients treated with regimens containing capecitabine. Polymorphisms in ABCB1, CDA, ENOSF1,and TYMS could help to predict specific and overall severe adverse reactions to capecitabine. Impact Journals LLC 2015-01-21 /pmc/articles/PMC4467446/ /pubmed/25691056 Text en Copyright: © 2015 García-González et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Clinical Research Paper García-González, Xandra Cortejoso, Lucía García, María I. García-Alfonso, Pilar Robles, Luis Grávalos, Cristina González-Haba, Eva Marta, Pellicer Sanjurjo, María López-Fernández, Luis A. Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer |
title | Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer |
title_full | Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer |
title_fullStr | Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer |
title_full_unstemmed | Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer |
title_short | Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer |
title_sort | variants in cda and abcb1 are predictors of capecitabine-related adverse reactions in colorectal cancer |
topic | Clinical Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467446/ https://www.ncbi.nlm.nih.gov/pubmed/25691056 |
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