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dc.contributor.authorSmyth, E
dc.contributor.authorZhang, S
dc.contributor.authorCunningham, D
dc.contributor.authorWotherspoon, A
dc.contributor.authorSoong, R
dc.contributor.authorPeckitt, C
dc.contributor.authorValeri, N
dc.contributor.authorFassan, M
dc.contributor.authorRugge, M
dc.contributor.authorOkines, AF
dc.contributor.authorAllum, W
dc.contributor.authorStenning, S
dc.contributor.authorNankivell, M
dc.contributor.authorLangley, RE
dc.contributor.authorTan, P
dc.coverage.spatialUnited States
dc.date.accessioned2017-10-20T08:42:57Z
dc.date.issued2017-10-02
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28972045
dc.identifier1078-0432.CCR-16-3142
dc.identifier.citationClin Cancer Res, 2017
dc.identifier.issn1078-0432
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/851
dc.identifier.doi10.1158/1078-0432.CCR-16-3142
dc.description.abstractPURPOSE: Germline polymorphisms may affect chemotherapy efficacy and toxicity. We examined the effect of polymorphisms in drug metabolism and DNA repair genes on pathological response rates, survival, and toxicity for patients randomised to surgery alone or perioperative ECF chemotherapy in the MRC MAGIC trial. EXPERIMENTAL DESIGN: DNA was extracted from non-tumor resection FFPE blocks. ERCC1, ERCC2, XRCC1, DYPD, and OPRT SNPs were evaluated using Sequenom, GSTP1, GSTT1 deletion and TYMS (TS) 5' 2R/3R using multiplex PCR. Post PCR amplification TS 2R/3R and GSTT1 samples underwent gel electrophoresis. RESULTS: Polymorphism data was available for 289/456 (63.4%) operated patients. No polymorphism was statistically significantly associated with pathological response to chemotherapy. Median overall survival (OS) for patients treated with surgery alone with any TS genotype was not different (1.76 years 2R/2R, 1.68 years 2R/3R, 2.09 years 3R/3R). Median OS for patients with a TS 2R/2R genotype treated with chemotherapy was not reached, whereas median OS for 2R/3R and 3R/3R patients were 1.44 and 1.60 years respectively (log rank p value 0.0053). The p value for the interaction between treatment arm and genotype (3R/3R and 3R/2R vs 2R/2R) was 0.029. No polymorphism was statistically significantly associated with chemotherapy toxicity. CONCLUSIONS: In MAGIC, patients with a TS 2R/2R genotype appeared to derive a larger benefit from perioperative ECF chemotherapy than patients with 3R containing genotypes. Further exploration of this potential predictive biomarker in this patient population is warranted.
dc.languageeng
dc.language.isoeng
dc.relation.isreplacedbyinternal/858
dc.relation.isreplacedbyhttps://repository.icr.ac.uk/handle/internal/858
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved
dc.titlePharmacogenetic analysis of the UK MRC MAGIC trial: association of polymorphisms with toxicity and survival in patients treated with perioperative ECF chemotherapy.
dc.typeJournal Article
dcterms.dateAccepted2017-09-26
rioxxterms.funderThe Institute of Cancer Research
rioxxterms.identifier.projectUnspecified
rioxxterms.versionofrecord10.1158/1078-0432.CCR-16-3142
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-10-02
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfClin Cancer Res
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine (RMH Smith Cunningham)/Medicine (RMH Smith Cunningham) (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished online
pubs.embargo.termsNot known
icr.researchteamMedicine (RMH Smith Cunningham)en_US
dc.contributor.icrauthorCunningham, Daviden


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