Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration

C Fernandez-Rozadilla; J B Cazier; V Moreno; M Crous-Bou; E Guinó; G Durán; M J Lamas; R López; S Candamio; E Gallardo; L Paré; M Baiget; D Páez; L A López-Fernández; L Cortejoso; M I García; L Bujanda; D González; V Gonzalo; L Rodrigo; J M Reñé; R Jover; A Brea-Fernández; M Andreu; X Bessa; X Llor; R Xicola; C Palles; I Tomlinson; S Castellví-Bel; A Castells; C Ruiz-Ponte; A Carracedo; EPICOLON Consortium

doi:10.1038/tpj.2012.2

Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration

C Fernandez-Rozadilla, J B Cazier, V Moreno, M Crous-Bou, E Guinó, G Durán, M J Lamas, R López, S Candamio, E Gallardo, L Paré, M Baiget, D Páez, L A López-Fernández, L Cortejoso, M I García, L Bujanda, D González, V Gonzalo, L RodrigoJ M Reñé, R Jover, A Brea-Fernández, M Andreu, X Bessa, X Llor, R Xicola, C Palles, I Tomlinson, S Castellví-Bel, A Castells, C Ruiz-Ponte, A Carracedo, EPICOLON Consortium

Cancer and Genomic Sciences

Research output: Contribution to journal › Article › peer-review

34 Citations (Scopus)

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.

Original language	English
Pages (from-to)	209-17
Number of pages	9
Journal	The Pharmacogenomics Journal
Volume	13
Issue number	3
DOIs	https://doi.org/10.1038/tpj.2012.2
Publication status	Published - Jun 2013

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/tpj.2012.2

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Fernandez-Rozadilla, C., Cazier, J. B., Moreno, V., Crous-Bou, M., Guinó, E., Durán, G., Lamas, M. J., López, R., Candamio, S., Gallardo, E., Paré, L., Baiget, M., Páez, D., López-Fernández, L. A., Cortejoso, L., García, M. I., Bujanda, L., González, D., Gonzalo, V., ... EPICOLON Consortium (2013). Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration. The Pharmacogenomics Journal, 13(3), 209-17. https://doi.org/10.1038/tpj.2012.2

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title = "Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration",

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.",

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",

author = "C Fernandez-Rozadilla and Cazier, {J B} and V Moreno and M Crous-Bou and E Guin{\'o} and G Dur{\'a}n and Lamas, {M J} and R L{\'o}pez and S Candamio and E Gallardo and L Par{\'e} and M Baiget and D P{\'a}ez and L{\'o}pez-Fern{\'a}ndez, {L A} and L Cortejoso and Garc{\'i}a, {M I} and L Bujanda and D Gonz{\'a}lez and V Gonzalo and L Rodrigo and Re{\~n}{\'e}, {J M} and R Jover and A Brea-Fern{\'a}ndez and M Andreu and X Bessa and X Llor and R Xicola and C Palles and I Tomlinson and S Castellv{\'i}-Bel and A Castells and C Ruiz-Ponte and A Carracedo and {EPICOLON Consortium}",

year = "2013",

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doi = "10.1038/tpj.2012.2",

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journal = "The Pharmacogenomics Journal",

issn = "1470-269X",

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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 & EPICOLON Consortium 2013, 'Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration', The Pharmacogenomics Journal, vol. 13, no. 3, pp. 209-17. https://doi.org/10.1038/tpj.2012.2

TY - JOUR

T1 - Pharmacogenomics in colorectal cancer

T2 - a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration

AU - Fernandez-Rozadilla, C

AU - Cazier, J B

AU - Moreno, V

AU - Crous-Bou, M

AU - Guinó, E

AU - Durán, G

AU - Lamas, M J

AU - López, R

AU - Candamio, S

AU - Gallardo, E

AU - Paré, L

AU - Baiget, M

AU - Páez, D

AU - López-Fernández, L A

AU - Cortejoso, L

AU - García, M I

AU - Bujanda, L

AU - González, D

AU - Gonzalo, V

AU - Rodrigo, L

AU - Reñé, J M

AU - Jover, R

AU - Brea-Fernández, A

AU - Andreu, M

AU - Bessa, X

AU - Llor, X

AU - Xicola, R

AU - Palles, C

AU - Tomlinson, I

AU - Castellví-Bel, S

AU - Castells, A

AU - Ruiz-Ponte, C

AU - Carracedo, A

AU - EPICOLON Consortium

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Biomarkers, Pharmacological

KW - Clinical Trials, Phase II as Topic

KW - Colorectal Neoplasms

KW - Drug-Related Side Effects and Adverse Reactions

KW - Female

KW - Fluorouracil

KW - Genome-Wide Association Study

KW - Genotyping Techniques

KW - Humans

KW - Leucovorin

KW - Male

KW - Middle Aged

KW - Organoplatinum Compounds

KW - Pharmacogenetics

KW - Polymorphism, Single Nucleotide

KW - Treatment Outcome

U2 - 10.1038/tpj.2012.2

DO - 10.1038/tpj.2012.2

M3 - Article

C2 - 22310351

SN - 1470-269X

VL - 13

SP - 209

EP - 217

JO - The Pharmacogenomics Journal

JF - The Pharmacogenomics Journal

IS - 3

ER -

Pharmacogenomics in colorectal cancer: a genome-wide association study to predict toxicity after 5-fluorouracil or FOLFOX administration

Abstract

Keywords

UN SDGs

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