title: Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer.
abstract: 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.
authors.affiliation: Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Xandra
authors.initials: X
authors.lastname: García-González
authors.affiliation: Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Cortejoso
authors.affiliation: Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: María I
authors.initials: MI
authors.lastname: García
authors.affiliation: Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: García-Alfonso
authors.affiliation: Department of Medical Oncology, Hospital Universitario Doce de Octubre, Instituto de Investigación Sanitaria Doce de Octubre, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Robles
authors.affiliation: Department of Medical Oncology, Hospital Universitario Doce de Octubre, Instituto de Investigación Sanitaria Doce de Octubre, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Grávalos
authors.affiliation: Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: González-Haba
authors.affiliation: Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Pellicer
authors.initials: P
authors.lastname: Marta
authors.affiliation: Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Sanjurjo
authors.affiliation: Department of Pharmacy, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: López-Fernández
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000069287:Capecitabine; D003564:Cytidine Deaminase
keywords: chemotherapy; flouropyrimidine; genetics; toxicity