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dc.contributor.authorSclafani, Fen_US
dc.contributor.authorChau, Ien_US
dc.contributor.authorCunningham, Den_US
dc.contributor.authorLampis, Aen_US
dc.contributor.authorHahne, JCen_US
dc.contributor.authorGhidini, Men_US
dc.contributor.authorLote, Hen_US
dc.contributor.authorZito, Den_US
dc.contributor.authorTabernero, Jen_US
dc.contributor.authorGlimelius, Ben_US
dc.contributor.authorCervantes, Aen_US
dc.contributor.authorBegum, Ren_US
dc.contributor.authorDe Castro, DGen_US
dc.contributor.authorWilson, SHen_US
dc.contributor.authorPeckitt, Cen_US
dc.contributor.authorEltahir, Zen_US
dc.contributor.authorWotherspoon, Aen_US
dc.contributor.authorTait, Den_US
dc.contributor.authorBrown, Gen_US
dc.contributor.authorOates, Jen_US
dc.contributor.authorBraconi, Cen_US
dc.contributor.authorValeri, Nen_US
dc.date.accessioned2016-11-07T14:41:16Z
dc.date.issued2016-09en_US
dc.identifier.citationCarcinogenesis, 2016, 37 (9), pp. 852 - 857en_US
dc.identifier.issn0143-3334en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/197
dc.identifier.eissn1460-2180en_US
dc.identifier.doi10.1093/carcin/bgw073en_US
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.en_US
dc.formatPrint-Electronicen_US
dc.format.extent852 - 857en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectHumansen_US
dc.subjectRectal Neoplasmsen_US
dc.subjectMicroRNAsen_US
dc.subjectAntineoplastic Combined Chemotherapy Protocolsen_US
dc.subjectNeoadjuvant Therapyen_US
dc.subjectRetrospective Studiesen_US
dc.subjectGenotypeen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectMaleen_US
dc.subjectChemoradiotherapyen_US
dc.titleSequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-06-28en_US
rioxxterms.versionofrecord10.1093/carcin/bgw073en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2016-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCarcinogenesisen_US
pubs.issue9en_US
pubs.notesNo embargoen_US
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/Gastrointestinal Cancer Biology and Genomics
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume37en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamSignal Transduction & Molecular Pharmacologyen_US
icr.researchteamMedicine (RMH Smith Cunningham)en_US
icr.researchteamGastrointestinal Cancer Biology and Genomicsen_US
dc.contributor.icrauthorCunningham, Daviden_US
dc.contributor.icrauthorGonzalez de Castro, Daviden_US
dc.contributor.icrauthorChau, Ianen_US
dc.contributor.icrauthorValeri, Nicolaen_US
dc.contributor.icrauthorBraconi, Chiaraen_US
dc.contributor.icrauthorHahne, Jensen_US
dc.contributor.icrauthorLampis, Andreaen_US


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