Pharmacogenetic prediction of clinical outcome in advanced colorectal cancer patients receiving oxaliplatin/5-fluorouracil as first-line chemotherapy
Paré Brunet, Laia (Institut d'Investigació Biomèdica Sant Pau)
Marcuello, E. (Institut d'Investigació Biomèdica Sant Pau)
Altés, Albert (Department d'Hematologia, Fundació Althaia)
Río, E. del (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Sedano, L. (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Salazar, J. (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Cortés, A. (Institut d'Investigació Biomèdica Sant Pau)
Barnadas i Molins, Agustí (Institut d'Investigació Biomèdica Sant Pau)
Baiget Bastús, Montserrat (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Universitat Autònoma de Barcelona

Date:	2008
Abstract:	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.
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	British Journal of Cancer, Vol. 99 (09 2008) , p. 1050-1055, ISSN 1532-1827

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

6 p, 127.1 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles