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dc.contributor.authorBarnett, G. C.
dc.contributor.authorThompson, D.
dc.contributor.authorFachal Vilar, Laura
dc.contributor.authorKerns, S.
dc.contributor.authorTalbot, C.
dc.contributor.authorElliott, R. M.
dc.contributor.authorDorling, L.
dc.contributor.authorColes, C. E.
dc.contributor.authorDearnaley, D. P.
dc.contributor.authorRosenstein, B. S.
dc.contributor.authorVega Gliemmo, Ana
dc.contributor.authorSymonds, P.
dc.contributor.authorYarnold, J.
dc.contributor.authorBaynes, C.
dc.contributor.authorMichailidou, K.
dc.contributor.authorDennis, J.
dc.contributor.authorTyrer, J. P.
dc.contributor.authorWilkinson, J. S.
dc.contributor.authorGómez Caamaño, Antonio 
dc.contributor.authorTanteles, G. A.
dc.contributor.authorPlatte, R.
dc.contributor.authorMayes, R.
dc.contributor.authorConroy, D.
dc.contributor.authorMaranian, M.
dc.contributor.authorLuccarini, C.
dc.contributor.authorGulliford, S. L.
dc.contributor.authorSydes, M. R.
dc.contributor.authorHall, E.
dc.contributor.authorHaviland, J.
dc.contributor.authorMisra, V.
dc.contributor.authorTitley, J.
dc.contributor.authorBentzen, S. M.
dc.contributor.authorPharoah, P. D.
dc.contributor.authorBurnet, N. G.
dc.contributor.authorDunning, A. M.
dc.contributor.authorWest, C. M.
dc.date.accessioned2017-06-07T07:15:56Z
dc.date.available2017-06-07T07:15:56Z
dc.date.issued2014
dc.identifier.issn0167-8140
dc.identifier.urihttp://hdl.handle.net/20.500.11940/4504
dc.description.abstractBACKGROUND AND PURPOSE: This study was designed to identify common single nucleotide polymorphisms (SNPs) associated with toxicity 2years after radiotherapy. MATERIALS AND METHODS: A genome wide association study was performed in 1850 patients from the RAPPER study: 1217 received adjuvant breast radiotherapy and 633 had radical prostate radiotherapy. Genotype associations with both overall and individual endpoints of toxicity were tested via univariable and multivariable regression. Replication of potentially associated SNPs was carried out in three independent patient cohorts who had radiotherapy for prostate (516 RADIOGEN and 862 Gene-PARE) or breast (355 LeND) cancer. RESULTS: Quantile-quantile plots show more associations at the P<5x10(-7) level than expected by chance (164 vs. 9 for the prostate cases and 29 vs. 4 for breast cases), providing evidence that common genetic variants are associated with risk of toxicity. Strongest associations were for individual endpoints rather than an overall measure of toxicity in all patients. However, in general, significant associations were not validated at a nominal 0.05 level in the replication cohorts. CONCLUSIONS: This largest GWAS to date provides evidence of true association between common genetic variants and toxicity. Associations with toxicity appeared to be tumour site-specific. Future GWAS require higher statistical power, in particular in the validation stage, to test clinically relevant effect sizes of SNP associations with individual endpoints, but the required sample sizes are achievable.
dc.language.isoeng
dc.subject.meshBreast Neoplasms
dc.subject.meshDose-Response Relationship, Radiation
dc.subject.meshFemale
dc.subject.meshGene Frequency
dc.subject.meshGenetic Predisposition to Disease
dc.subject.meshGenetic Variation
dc.subject.meshGenome-Wide Association Study
dc.subject.meshGenotype
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshProspective Studies
dc.subject.meshProstatic Neoplasms
dc.subject.meshRadiation Injuries
dc.subject.meshRadiotherapy, Adjuvant
dc.subject.meshRadiotherapy, Intensity-Modulated
dc.subject.meshAdverse effects
dc.subject.meshGenetics
dc.subject.meshGenome-wide association scan
dc.subject.meshLate toxicity
dc.subject.meshRadiotherapy
dc.titleA genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity
dc.typeArtigoes
dc.authorsophosBarnett, G. C.
dc.authorsophosThompson, D.
dc.authorsophosFachal, L.
dc.authorsophosKerns, S.
dc.authorsophosTalbot, C.
dc.authorsophosElliott, R. M.
dc.authorsophosDorling, L.
dc.authorsophosColes, C. E.
dc.authorsophosDearnaley, D. P.
dc.authorsophosRosenstein, B. S.
dc.authorsophosVega, A.
dc.authorsophosSymonds, P.
dc.authorsophosYarnold, J.
dc.authorsophosBaynes, C.
dc.authorsophosMichailidou, K.
dc.authorsophosDennis, J.
dc.authorsophosTyrer, J. P.
dc.authorsophosWilkinson, J. S.
dc.authorsophosGómez-Caamaño, A.
dc.authorsophosTanteles, G. A.
dc.authorsophosPlatte, R.
dc.authorsophosMayes, R.
dc.authorsophosConroy, D.
dc.authorsophosMaranian, M.
dc.authorsophosLuccarini, C.
dc.authorsophosGulliford, S. L.
dc.authorsophosSydes, M. R.
dc.authorsophosHall, E.
dc.authorsophosHaviland, J.
dc.authorsophosMisra, V.
dc.authorsophosTitley, J.
dc.authorsophosBentzen, S. M.
dc.authorsophosPharoah, P. D.
dc.authorsophosBurnet, N. G.
dc.authorsophosDunning, A. M.
dc.authorsophosWest, C. M.
dc.identifier.doi10.1016/j.radonc.2014.02.012
dc.identifier.isi339150100003
dc.identifier.pmid24785509
dc.identifier.sophos14572
dc.issue.number2
dc.journal.titleRADIOTHERAPY AND ONCOLOGY
dc.organizationConsellería de Sanidade::Fundación pública Galega de Medicina Xenómica
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago::IDIS.- Instituto de investigaciones sanitarias de Santiago
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago - Complexo Hospitalario Universitario de Santiago::Oncología Radioterápica
dc.page.initial178
dc.page.final85
dc.rights.accessRightsopenAccess
dc.typesophosArtículo Original
dc.volume.number111


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