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

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), eithe...

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Authors: Fernandez-Rozadilla, C, Cazier, JB, Moreno, V, Crous-Bou, M, Guino, E, Duran, G, Lamas, MJ, Lopez, R, Candamio, S, Gallardo, E, Pare, L, Baiget, M, Paez, D, Lopez-Fernandez, LA, Cortejoso, L, Garcia, MI, Bujanda, L, Gonzalez, D, Gonzalo, V, Rodrigo, L, Rene, JM, Jover, R, Brea-Fernandez, A, Andreu, M, Bessa, X, Llor, X, Xicola, R, Palles, C, Tomlinson, I, Castellvi-Bel, S, Castells, A, Ruiz-Ponte, C, Carracedo, A
Format: article
Status:Published version
Publication Date:2013
Country:España
Institution:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repository:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p9991
Online Access:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=9991
Access Level:Open access
Keyword:ADR
colorectal cancer
FOLFOX
GWAS
5-fluorouracil
Description
Summary: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.

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