Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration.
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.
Galician 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.
C
C
Fernandez-Rozadilla
J B
JB
Cazier
V
V
Moreno
M
M
Crous-Bou
E
E
Guinó
G
G
Durán
M J
MJ
Lamas
R
R
López
S
S
Candamio
E
E
Gallardo
L
L
Paré
M
M
Baiget
D
D
Páez
L A
LA
López-Fernández
L
L
Cortejoso
M I
MI
García
L
L
Bujanda
D
D
González
V
V
Gonzalo
L
L
Rodrigo
J M
JM
Reñé
R
R
Jover
A
A
Brea-Fernández
M
M
Andreu
X
X
Bessa
X
X
Llor
R
R
Xicola
C
C
Palles
I
I
Tomlinson
S
S
Castellví-Bel
A
A
Castells
C
C
Ruiz-Ponte
A
A
Carracedo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016896:Treatment Outcome
D054316:Biomarkers, Pharmacological; D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil