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Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy
Paré, L (Hospital de la Santa Creu i Sant Pau)
Marcuello, E (Departament d'Oncologia Clínica. Hospital de la Santa Creu i Sant Pau)
Altés, A (Department d'Hematologia, Fundació Althaia)
Río, E del (Center for Biomedical Research on Rare Diseases (CIBERER))
Sedano, L (Center for Biomedical Research on Rare Diseases (CIBERER))
Salazar, J (Center for Biomedical Research on Rare Diseases (CIBERER))
Cortés, A (Department de Genètica, Hospital de la Santa Creu i Sant Pau)
Barnadas, Agustí (Hospital de la Santa Creu i Sant Pau. Department d'Oncologia Clínica)
Baiget Bastus, Montserrat (Center for Biomedical Research on Rare Diseases (CIBERER))

Fecha: 2008
Resumen: To determine whether molecular parameters could be partly responsible for resistance or sensitivity to oxaliplatin (OX)-based chemotherapy used as first-line treatment in advanced colorectal cancer (CRC). We studied the usefulness of the excision repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD), XRCC1 and GSTP1 polymorphisms as predictors of clinical outcome in these patients. We treated 126 CRC patients with a first-line OX/5-fluorouracil chemotherapeutic regimen. Genetic polymorphisms were determined by real-time PCR on an ABI PRISM 7000, using DNA from peripheral blood. Clinical response (CR), progression-free survival (PFS) and overall survival (OS) were evaluated according to each genotype. In the univariate analysis for CR, ERCC1 -118 and XPD 751 polymorphisms were significant (P =0. 02 and P =0. 05, respectively). After adjustment for the most relevant clinical variables, only ERCC1 -118 retained significance (P =0. 008). In the univariate analysis for PFS, ERCC1 -118 and XPD 751 were significant (P =0. 003 and P =0. 009, respectively). In the multivariant analysis, only the XPD 751 was significant for PFS (P =0. 02). Finally, ERCC1 -118 and XPD 751 polymorphisms were significant in the univariate analysis for OS (P =0. 006 and P =0. 015, respectively). Both genetic variables remained significant in the multivariate Cox survival analysis (P =0. 022 and P =0. 03). Our data support the hypothesis that enhanced DNA repair diminishes the benefit of platinum-based treatments.
Derechos: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials i que es distribueixin sota la mateixa llicència que regula l'obra original. Cal que es reconegui l'autoria de l'obra original. Creative Commons
Lengua: Anglès.
Documento: article ; recerca ; publishedVersion
Publicado en: British Journal of Cancer, Vol. 99 (09 2008) , p. 1050-1055, ISSN 1532-1827

DOI: 10.1038/sj.bjc.6604671
PMID: 18797464


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