AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin

J B Kjersem, M. Thomsen, T Guren, J Hamfjord, G Carlsson, B Gustavsson, T Ikdahl, G Indrebø, P Pfeiffer, O Lingjærde, K M Tveit, Y Wettergren, E H Kure

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Resumé

The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples from 519 mCRC patients treated with first-line 5-fluorouracil and oxaliplatin +/- cetuximab for 17 SNPs in 10 genes involved in membrane transport (ABCC1 and ABCC2), drug biotransformation (GSTP1 and AGXT) and DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XPG and MSH6). The AGXT-rs34116584 and the ERCC2-rs238406 polymorphisms were significantly associated with progression-free survival (P=0.002 and P=0.001, respectively). Associations between 18 toxicity variables and SNPs were identified, although none were significant after Bonferroni correction for multiple comparisons. The study identified SNPs of potential use as markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.54.

OriginalsprogEngelsk
TidsskriftThe Pharmacogenomics Journal
Vol/bind16
Udgave nummer3
Sider (fra-til)272-279
ISSN1470-269X
DOI
StatusUdgivet - 2016

Fingeraftryk

oxaliplatin
Fluorouracil
Single Nucleotide Polymorphism
Colorectal Neoplasms
Pharmacogenetics
Pharmaceutical Preparations
Disease-Free Survival
Publications
Membranes

Citer dette

Kjersem, J B ; Thomsen, M. ; Guren, T ; Hamfjord, J ; Carlsson, G ; Gustavsson, B ; Ikdahl, T ; Indrebø, G ; Pfeiffer, P ; Lingjærde, O ; Tveit, K M ; Wettergren, Y ; Kure, E H. / AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin. I: The Pharmacogenomics Journal. 2016 ; Bind 16, Nr. 3. s. 272-279.
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title = "AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin",
abstract = "The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples from 519 mCRC patients treated with first-line 5-fluorouracil and oxaliplatin +/- cetuximab for 17 SNPs in 10 genes involved in membrane transport (ABCC1 and ABCC2), drug biotransformation (GSTP1 and AGXT) and DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XPG and MSH6). The AGXT-rs34116584 and the ERCC2-rs238406 polymorphisms were significantly associated with progression-free survival (P=0.002 and P=0.001, respectively). Associations between 18 toxicity variables and SNPs were identified, although none were significant after Bonferroni correction for multiple comparisons. The study identified SNPs of potential use as markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.54.",
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Kjersem, JB, Thomsen, M, Guren, T, Hamfjord, J, Carlsson, G, Gustavsson, B, Ikdahl, T, Indrebø, G, Pfeiffer, P, Lingjærde, O, Tveit, KM, Wettergren, Y & Kure, EH 2016, 'AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin', The Pharmacogenomics Journal, bind 16, nr. 3, s. 272-279. https://doi.org/10.1038/tpj.2015.54

AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin. / Kjersem, J B; Thomsen, M.; Guren, T; Hamfjord, J; Carlsson, G; Gustavsson, B; Ikdahl, T; Indrebø, G; Pfeiffer, P; Lingjærde, O; Tveit, K M; Wettergren, Y; Kure, E H.

I: The Pharmacogenomics Journal, Bind 16, Nr. 3, 2016, s. 272-279.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - AGXT and ERCC2 polymorphisms are associated with clinical outcome in metastatic colorectal cancer patients treated with 5-FU/oxaliplatin

AU - Kjersem, J B

AU - Thomsen, M.

AU - Guren, T

AU - Hamfjord, J

AU - Carlsson, G

AU - Gustavsson, B

AU - Ikdahl, T

AU - Indrebø, G

AU - Pfeiffer, P

AU - Lingjærde, O

AU - Tveit, K M

AU - Wettergren, Y

AU - Kure, E H

PY - 2016

Y1 - 2016

N2 - The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples from 519 mCRC patients treated with first-line 5-fluorouracil and oxaliplatin +/- cetuximab for 17 SNPs in 10 genes involved in membrane transport (ABCC1 and ABCC2), drug biotransformation (GSTP1 and AGXT) and DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XPG and MSH6). The AGXT-rs34116584 and the ERCC2-rs238406 polymorphisms were significantly associated with progression-free survival (P=0.002 and P=0.001, respectively). Associations between 18 toxicity variables and SNPs were identified, although none were significant after Bonferroni correction for multiple comparisons. The study identified SNPs of potential use as markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.54.

AB - The objective of the study was to investigate whether specific single nucleotide polymorphisms (SNPs) with influence on drug transport, biotransformation and repair mechanisms are associated with treatment outcome and toxicity in metastatic colorectal cancer (mCRC). We genotyped blood samples from 519 mCRC patients treated with first-line 5-fluorouracil and oxaliplatin +/- cetuximab for 17 SNPs in 10 genes involved in membrane transport (ABCC1 and ABCC2), drug biotransformation (GSTP1 and AGXT) and DNA repair (ERCC1, ERCC2, XRCC1, XRCC3, XPG and MSH6). The AGXT-rs34116584 and the ERCC2-rs238406 polymorphisms were significantly associated with progression-free survival (P=0.002 and P=0.001, respectively). Associations between 18 toxicity variables and SNPs were identified, although none were significant after Bonferroni correction for multiple comparisons. The study identified SNPs of potential use as markers of clinical outcome in oxaliplatin-treated mCRC patients. If validated in other studies, they could improve the selection of therapy in mCRC.The Pharmacogenomics Journal advance online publication, 11 August 2015; doi:10.1038/tpj.2015.54.

U2 - 10.1038/tpj.2015.54

DO - 10.1038/tpj.2015.54

M3 - Journal article

VL - 16

SP - 272

EP - 279

JO - The Pharmacogenomics Journal

JF - The Pharmacogenomics Journal

SN - 1470-269X

IS - 3

ER -