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dc.contributor.authorApplebaum, MAen_US
dc.contributor.authorVaksman, Zen_US
dc.contributor.authorLee, SMen_US
dc.contributor.authorHungate, EAen_US
dc.contributor.authorHenderson, TOen_US
dc.contributor.authorLondon, WBen_US
dc.contributor.authorPinto, Nen_US
dc.contributor.authorVolchenboum, SLen_US
dc.contributor.authorPark, JRen_US
dc.contributor.authorNaranjo, Aen_US
dc.contributor.authorHero, Ben_US
dc.contributor.authorPearson, ADen_US
dc.contributor.authorStranger, BEen_US
dc.contributor.authorCohn, SLen_US
dc.contributor.authorDiskin, SJen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-02-20T11:58:48Z
dc.date.issued2017-02en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28033528en_US
dc.identifierS0959-8049(16)32600-4en_US
dc.identifier.citationEur J Cancer, 2017, 72 pp. 177 - 185en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1397
dc.identifier.eissn1879-0852en_US
dc.identifier.doi10.1016/j.ejca.2016.11.022en_US
dc.description.abstractBACKGROUND: The incidence of second malignant neoplasm (SMN) within the first ten years of diagnosis in high-risk neuroblastoma patients treated with modern, intensive therapy is unknown. Further, the underlying germline genetics that contribute to SMN in these survivors are not known. METHODS: The International Neuroblastoma Risk Group (INRG) database of patients diagnosed from 1990 to 2010 was analysed. SMN risk was accessed by cumulative incidence, standardised incidence ratios (SIRs) and absolute excess risk. A candidate gene-based association study evaluated genetic susceptibility to SMN in neuroblastoma survivors. RESULTS: Of the 5987 patients in the INRG database with SMN data enrolled in a clinical trial, 43 (0.72%) developed a SMN. The 10-year cumulative incidence of SMN for high-risk patients was 1.8% (95% confidence interval [CI] 1.0-2.6%) compared with 0.38% (95% CI: 0.22-0.94%) for low-risk patients (P = 0.01). High-risk patients had an almost 18-fold higher incidence of SMN compared to age- and sex-matched controls (SIR = 17.5 (95% CI: 11.4-25.3), absolute excess risk = 27.6). For patients treated on high- and intermediate-risk clinical trials, the SIR of acute myelogenous leukaemia was 106.8 (95% CI: 28.7-273.4) and 127.7 (95%CI: 25.7-373.3), respectively. Variants implicating DNA repair genes XRCC3 (rs861539: P = 0.006; odds ratio: 2.04, 95%CI: 1.19-3.46) and MSH2 (rs17036651: P = 0.009; odds ratio: 0.26, 95% CI: 0.08-0.81) were associated with SMN. CONCLUSION: The intensive multi-modality treatment strategy currently used to treat high-risk neuroblastoma is associated with a significantly increased risk of secondary acute myelogenous leukaemia. Defining the interactions of treatment exposures and genetic factors that promote the development of SMN is critical for optimising survivorship care.en_US
dc.format.extent177 - 185en_US
dc.languageengen_US
dc.language.isoengen_US
dc.subjectGenetic association studyen_US
dc.subjectINRGen_US
dc.subjectNeuroblastomaen_US
dc.subjectSecond malignant neoplasmsen_US
dc.subjectAdolescenten_US
dc.subjectAdulten_US
dc.subjectChilden_US
dc.subjectChild, Preschoolen_US
dc.subjectCombined Modality Therapyen_US
dc.subjectDNA Repairen_US
dc.subjectFemaleen_US
dc.subjectGenetic Association Studiesen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectHumansen_US
dc.subjectIncidenceen_US
dc.subjectInfanten_US
dc.subjectLeukemia, Myeloid, Acuteen_US
dc.subjectMaleen_US
dc.subjectNeoplasms, Second Primaryen_US
dc.subjectNeuroblastomaen_US
dc.subjectRisk Assessmenten_US
dc.subjectRisk Factorsen_US
dc.subjectSurvivorsen_US
dc.subjectYoung Adulten_US
dc.titleNeuroblastoma survivors are at increased risk for second malignancies: A report from the International Neuroblastoma Risk Group Project.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-11-15en_US
rioxxterms.versionofrecord10.1016/j.ejca.2016.11.022en_US
rioxxterms.licenseref.startdate2017-02en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfEur J Canceren_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume72en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorMarsden,en_US


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