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dc.contributor.authorKerns, SL
dc.contributor.authorDorling, L
dc.contributor.authorFachal, L
dc.contributor.authorBentzen, S
dc.contributor.authorPharoah, PDP
dc.contributor.authorBarnes, DR
dc.contributor.authorGómez-Caamaño, A
dc.contributor.authorCarballo, AM
dc.contributor.authorDearnaley, DP
dc.contributor.authorPeleteiro, P
dc.contributor.authorGulliford, SL
dc.contributor.authorHall, E
dc.contributor.authorMichailidou, K
dc.contributor.authorCarracedo, Á
dc.contributor.authorSia, M
dc.contributor.authorStock, R
dc.contributor.authorStone, NN
dc.contributor.authorSydes, MR
dc.contributor.authorTyrer, JP
dc.contributor.authorAhmed, S
dc.contributor.authorParliament, M
dc.contributor.authorOstrer, H
dc.contributor.authorRosenstein, BS
dc.contributor.authorVega, A
dc.contributor.authorBurnet, NG
dc.contributor.authorDunning, AM
dc.contributor.authorBarnett, GC
dc.contributor.authorWest, CML
dc.contributor.authorRadiogenomics Consortium
dc.date.accessioned2016-09-05T10:50:51Z
dc.date.issued2016-08
dc.identifier.citationEBioMedicine, 2016, 10 pp. 150 - 163
dc.identifier.issn2352-3964
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/89
dc.identifier.eissn2352-3964
dc.identifier.doi10.1016/j.ebiom.2016.07.022
dc.description.abstractNearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.
dc.formatPrint-Electronic
dc.format.extent150 - 163
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectRadiogenomics Consortium
dc.subjectHumans
dc.subjectProstatic Neoplasms
dc.subjectGenetic Markers
dc.subjectNeoplasm Staging
dc.subjectTreatment Outcome
dc.subjectCombined Modality Therapy
dc.subjectRadiotherapy
dc.subjectOdds Ratio
dc.subjectCohort Studies
dc.subjectGenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectAlleles
dc.subjectRadiation Tolerance
dc.subjectQuality of Life
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectMale
dc.subjectGenome-Wide Association Study
dc.titleMeta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.
dc.typeJournal Article
dcterms.dateAccepted2016-07-18
rioxxterms.versionofrecord10.1016/j.ebiom.2016.07.022
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEBioMedicine
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/ICR-CTSU Urology and Head and Neck Trials Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiotherapy Physics Modelling
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/ICR-CTSU Urology and Head and Neck Trials Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Clinical Academic Radiotherapy (Dearnaley)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Radiotherapy Physics Modelling
pubs.publication-statusPublished
pubs.volume10
pubs.embargo.termsNo embargo
icr.researchteamICR-CTSU Urology and Head and Neck Trials Teamen_US
icr.researchteamClinical Academic Radiotherapy (Dearnaley)en_US
icr.researchteamRadiotherapy Physics Modellingen_US
dc.contributor.icrauthorDearnaley, Daviden
dc.contributor.icrauthorHall, Emmaen
dc.contributor.icrauthorGulliford, Sarahen


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