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Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or
C Fernandez-Rozadilla1, J B Cazier, V Moreno
1Galician Public Foundation of Genomic Medicine-FPGMX-Centro de Investigación Biomédica en Red de Enfermedades Raras-CIBERER-Genomics Medicine Group-Hospital Clínico Santiago de Compostela-University of Santiago de Compostela, Santiago de Compostela, Spain.
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.
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