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Pharmacogenomics J. 2016 Jun;16(3):272-9. doi: 10.1038/tpj.2015.54. Epub 2015 Aug 11.

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

Author information

1
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
2
Department of Oncology, Oslo University Hospital, Oslo, Norway.
3
Department of Surgery, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden.
4
Akershus University Hospital, Lørenskog, Norway.
5
Department of Oncology, Ålesund Hospital, Møre and Romsdal Hospital Trust, Ålesund, Norway.
6
Department of Oncology, Odense University Hospital, Sdr Boulevard 29, Odense C, Denmark.
7
Department of Computer Science, University of Oslo, Oslo, Norway.
8
K.G. Jebsen Center for Breast Cancer Research, Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00145314.

PMID:
26261061
DOI:
10.1038/tpj.2015.54
[Indexed for MEDLINE]

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