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

C. Fernandez-Rozadilla, J. B. Cazier, V. Moreno, M. Crous-Bou, E. Guinó, G. Durán, M. J. Lamas, R. López, S. Candamio, E. Gallardo, L. Paré, M. Baiget, D. Páez, L. A. López-Fernández, L. Cortejoso, M. I. García, L. Bujanda, D. González, V. Gonzalo, L. RodrigoJ. M. Reñé, R. Jover, A. Brea-Fernández, M. Andreu, X. Bessa, X. Llor, R. Xicola, C. Palles, I. Tomlinson, S. Castellví-Bel, A. Castells, C. Ruiz-Ponte, A. Carracedo

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    36 Citations (Scopus)

    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. © 2013 Macmillan Publishers Limited. All rights reserved 1470-269X/13.
    Original languageEnglish
    Pages (from-to)209-217
    JournalPharmacogenomics Journal
    Volume13
    Issue number3
    DOIs
    Publication statusPublished - 1 Jun 2013

    Keywords

    • 5-fluorouracil
    • ADR
    • colorectal cancer
    • FOLFOX
    • GWAS

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