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Pharmacogenomics J. 2013 Jun;13(3):209-17. doi: 10.1038/tpj.2012.2. Epub 2012 Feb 7.

Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration.

Collaborators (128)

Morillas JD, Muñoz R, Manzano M, Colina F, Díaz J, Ibarrola C, López G, Ibáñez A, Castells A, Piñol V, Castellví-Bel S, Balaguer F, Gonzalo V, Ocaña T, Giráldez MD, Pellisé M, Serradesanferm A, Moreira L, Cuatrecasas M, Piqué JM, Lanas Á, Alcedo J, Ortego J, Cubiella J, Soledad Díez M, Salgado M, Sánchez E, Vega M, Andreu M, Abuli A, Bessa X, Iglesias M, Seoane A, Bory F, Navarro G, Bellosillo B, Dedeu JM, Álvarez C, Gonzalez B, Bujanda L, Cosme Á, Gil I, Larzabal M, Placer C, del Mar Ramírez M, Hijona E, Enríquez-Navascués JM, Elosegui JL, Jover R, Payá A, Alenda C, Sempere L, Acame N, Rojas E, Pérez-Carbonell L, Rigau J, Serrano Á, Giménez A, Saló J, Batiste-Alentorn E, Autonell J, Barniol R, García AM, Carballo F, Bienvenido A, Sanz E, González F, Sánchez J, Ono A, Medina E, Latorre M, Cuquerella J, Canelles P, Martorell M, García JÁ, Quiles F, Orti E, Clofent J, Seoane J, Tardío A, Sanchez E, de Castro ML, Tardío A, Clofent J, Hernández V, Llor X, Xicola RM, Piñol M, Rosinach M, Roca A, Pons E, Hernández JM, Gassull MA, Fernández-Bañares F, Viver JM, Salas A, Espinós J, Forné M, Esteve M, Reñé JM, Piñol C, Buenestado J, Viñas J, Quintero E, Nicolás D, Parra A, Martín A, Argüello L, Pons V, Pertejo V, Sala T, Gonzalez D, Roman E, Ramon T, Poca M, Concepción MM, Martin M, Pétriz L, Martinez D, Carracedo A, Ruiz-Ponte C, Fernández-Rozadilla C, Magdalena-Castro MJ, Riestra S, Rodrigo L, Fernández J, Cabriada JL, Carreño L.

Abstract

The development of genotyping technologies has allowed for wider screening for inherited causes of variable outcomes following drug administration. We have performed a genome-wide association study (GWAS) on 221 colorectal cancer (CRC) patients that had been treated with 5-fluorouracil (5-FU), either alone or in combination with oxaliplatin (FOLFOX). A validation set of 791 patients was also studied. Seven SNPs (rs16857540, rs2465403, rs10876844, rs10784749, rs17626122, rs7325568 and rs4243761) showed evidence of association (pooled P-values 0.020, 9.426E-03, 0.010, 0.017, 0.042, 2.302E-04, 2.803E-03) with adverse drug reactions (ADRs). This is the first study to explore the genetic basis of inter-individual variation in toxicity responses to the administration of 5-FU or FOLFOX in CRC patients on a genome-wide scale.

PMID:
22310351
[PubMed - indexed for MEDLINE]
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