Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration
Por:
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
Publicada:
1 jun 2013
Resumen:
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.
Filiaciones:
Fernandez-Rozadilla, C:
Univ Santiago de Compostela, Galician Publ Fdn Genom Med FPGMX, CIBERER, Genom Med Grp,Hosp Clin Santiago de Compostela, Santiago De Compostela, Spain
Cazier, JB:
Univ Oxford, Nuffield Dept Med, Oxford, England
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Moreno, V:
CIBERESP, Bellvitge Biomed Res Ctr IDIBELL, Catalan Inst Oncol ICO, Canc Prevent & Control Program, Barcelona, Spain
Univ Barcelona, Fac Med, Barcelona 7, Spain
Crous-Bou, M:
CIBERESP, Bellvitge Biomed Res Ctr IDIBELL, Catalan Inst Oncol ICO, Canc Prevent & Control Program, Barcelona, Spain
Guino, E:
CIBERESP, Bellvitge Biomed Res Ctr IDIBELL, Catalan Inst Oncol ICO, Canc Prevent & Control Program, Barcelona, Spain
Duran, G:
CHUS, Oncol Pharm Unit, Santiago De Compostela, Spain
Lamas, MJ:
CHUS, Oncol Pharm Unit, Santiago De Compostela, Spain
Lopez, R:
CHUS, Dept Clin Oncol, Santiago De Compostela, Spain
Candamio, S:
CHUS, Dept Clin Oncol, Santiago De Compostela, Spain
Gallardo, E:
CHUS, Dept Clin Oncol, Santiago De Compostela, Spain
Pare, L:
Univ Autonoma Barcelona, Mol Genet Unit, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Baiget, M:
Univ Autonoma Barcelona, Mol Genet Unit, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Paez, D:
Univ Autonoma Barcelona, Dept Med Oncol, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Lopez-Fernandez, LA:
Hosp Gen Univ Gregorio Maranon, Serv Farm, Pharmacogenet & Pharmacogen Lab, Madrid, Spain
Cortejoso, L:
Hosp Gen Univ Gregorio Maranon, Serv Farm, Pharmacogenet & Pharmacogen Lab, Madrid, Spain
Garcia, MI:
Hosp Gen Univ Gregorio Maranon, Serv Farm, Pharmacogenet & Pharmacogen Lab, Madrid, Spain
Bujanda, L:
Univ Basque Country, CIBERehd, Donostia Hosp, Dept Gastroenterol, San Sebastian, Spain
Gonzalez, D:
Univ Autonoma Barcelona, Dept Gastroenterol, Hosp Santa Creu & St Pau, E-08193 Barcelona, Spain
Gonzalo, V:
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBEREHD,IDIBAPS, Barcelona, Spain
Rodrigo, L:
Hosp Univ Cent Asturias, Dept Gastroenterol, Oviedo, Spain
Rene, JM:
Univ Lleida, Dept Gastroenterol, Hosp Univ Arnau de Vilanova, IRBLleida, Lleida, Spain
Jover, R:
Hosp Gen Alicante, Dept Gastroenterol, Alicante, Spain
Brea-Fernandez, A:
Univ Santiago de Compostela, Galician Publ Fdn Genom Med FPGMX, CIBERER, Genom Med Grp,Hosp Clin Santiago de Compostela, Santiago De Compostela, Spain
Andreu, M:
Hosp del Mar, Dept Gastroenterol, Barcelona, Spain
Bessa, X:
Hosp del Mar, Dept Gastroenterol, Barcelona, Spain
Llor, X:
Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL USA
Xicola, R:
Univ Illinois, Sect Digest Dis & Nutr, Chicago, IL USA
Palles, C:
Univ Oxford, Nuffield Dept Med, Oxford, England
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Tomlinson, I:
Univ Oxford, Nuffield Dept Med, Oxford, England
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England
Univ Oxford, NIHR Comprehens Biomed Res Ctr, Oxford, England
Castellvi-Bel, S:
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBEREHD,IDIBAPS, Barcelona, Spain
Castells, A:
Univ Barcelona, Dept Gastroenterol, Hosp Clin, CIBEREHD,IDIBAPS, Barcelona, Spain
Ruiz-Ponte, C:
Univ Santiago de Compostela, Galician Publ Fdn Genom Med FPGMX, CIBERER, Genom Med Grp,Hosp Clin Santiago de Compostela, Santiago De Compostela, Spain
Carracedo, A:
Univ Santiago de Compostela, Galician Publ Fdn Genom Med FPGMX, CIBERER, Genom Med Grp,Hosp Clin Santiago de Compostela, Santiago De Compostela, Spain
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