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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.

Original publication

DOI

10.1038/tpj.2012.2

Type

Journal article

Journal

Pharmacogenomics J

Publication Date

06/2013

Volume

13

Pages

209 - 217

Keywords

Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Pharmacological, Clinical Trials, Phase II as Topic, Colorectal Neoplasms, Drug-Related Side Effects and Adverse Reactions, Female, Fluorouracil, Genome-Wide Association Study, Genotyping Techniques, Humans, Leucovorin, Male, Middle Aged, Organoplatinum Compounds, Pharmacogenetics, Polymorphism, Single Nucleotide, Treatment Outcome