Pharmacogenomics in colorectal cancer: A genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration
Fernandez-Rozadilla C., Cazier JB., Moreno V., Crous-Bou M., Guinó E., Durán G., Lamas MJ., López R., Candamio S., Gallardo E., Paré L., Baiget M., Páez D., López-Fernández LA., Cortejoso L., García MI., Bujanda L., González D., Gonzalo V., Rodrigo L., Reñé JM., Jover R., Brea-Fernández A., Andreu M., Bessa X., Llor X., Xicola R., Palles C., Tomlinson I., Castellví-Bel S., Castells A., Ruiz-Ponte C., Carracedo A.
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.