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dc.contributor.authorSclafani, F
dc.contributor.authorChau, I
dc.contributor.authorCunningham, D
dc.contributor.authorLampis, A
dc.contributor.authorHahne, JC
dc.contributor.authorGhidini, M
dc.contributor.authorLote, H
dc.contributor.authorZito, D
dc.contributor.authorTabernero, J
dc.contributor.authorGlimelius, B
dc.contributor.authorCervantes, A
dc.contributor.authorBegum, R
dc.contributor.authorDe Castro, DG
dc.contributor.authorWilson, SH
dc.contributor.authorPeckitt, C
dc.contributor.authorEltahir, Z
dc.contributor.authorWotherspoon, A
dc.contributor.authorTait, D
dc.contributor.authorBrown, G
dc.contributor.authorOates, J
dc.contributor.authorBraconi, C
dc.contributor.authorValeri, N
dc.date.accessioned2016-11-07T14:41:16Z
dc.date.issued2016-09-01
dc.identifier.citationCarcinogenesis, 2016, 37 (9), pp. 852 - 857
dc.identifier.issn0143-3334
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/197
dc.identifier.eissn1460-2180
dc.identifier.doi10.1093/carcin/bgw073
dc.description.abstractSingle nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX ± Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14-1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61-3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52-3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome.
dc.formatPrint-Electronic
dc.format.extent852 - 857
dc.languageeng
dc.language.isoeng
dc.publisherOXFORD UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectRectal Neoplasms
dc.subjectMicroRNAs
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectNeoadjuvant Therapy
dc.subjectRetrospective Studies
dc.subjectGenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAdult
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subjectChemoradiotherapy
dc.titleSequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients.
dc.typeJournal Article
dcterms.dateAccepted2016-06-28
rioxxterms.versionofrecord10.1093/carcin/bgw073
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCarcinogenesis
pubs.issue9
pubs.notesNo embargo
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
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/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Signal Transduction & Molecular Pharmacology
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/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gastrointestinal Cancer Biology and Genomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume37
pubs.embargo.termsNo embargo
icr.researchteamSignal Transduction & Molecular Pharmacology
icr.researchteamMedicine (RMH Smith Cunningham)
icr.researchteamEvolutionary Genomics & Modelling
icr.researchteamGastrointestinal Cancer Biology and Genomics
dc.contributor.icrauthorLampis, Andrea
dc.contributor.icrauthorHahne, Jens
dc.contributor.icrauthorBraconi, Chiara
dc.contributor.icrauthorValeri, Nicola


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