dc.contributor.author | Ahmed, M | |
dc.contributor.author | Dorling, L | |
dc.contributor.author | Kerns, S | |
dc.contributor.author | Fachal, L | |
dc.contributor.author | Elliott, R | |
dc.contributor.author | Partliament, M | |
dc.contributor.author | Rosenstein, BS | |
dc.contributor.author | Vega, A | |
dc.contributor.author | Gómez-Caamaño, A | |
dc.contributor.author | Barnett, G | |
dc.contributor.author | Dearnaley, DP | |
dc.contributor.author | Hall, E | |
dc.contributor.author | Sydes, M | |
dc.contributor.author | Burnet, N | |
dc.contributor.author | Pharoah, PDP | |
dc.contributor.author | Eeles, R | |
dc.contributor.author | West, CML | |
dc.date.accessioned | 2016-08-26T15:31:13Z | |
dc.date.issued | 2016-05-10 | |
dc.identifier.citation | British journal of cancer, 2016, 114 (10), pp. 1165 - 1174 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/82 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/bjc.2016.94 | |
dc.description.abstract | BACKGROUND: Numerous germline single-nucleotide polymorphisms increase susceptibility to prostate cancer, some lying near genes involved in cellular radiation response. This study investigated whether prostate cancer patients with a high genetic risk have increased toxicity following radiotherapy. METHODS: The study included 1560 prostate cancer patients from four radiotherapy cohorts: RAPPER (n=533), RADIOGEN (n=597), GenePARE (n=290) and CCI (n=150). Data from genome-wide association studies were imputed with the 1000 Genomes reference panel. Individuals were genetically similar with a European ancestry based on principal component analysis. Genetic risks were quantified using polygenic risk scores. Regression models tested associations between risk scores and 2-year toxicity (overall, urinary frequency, decreased stream, rectal bleeding). Results were combined across studies using standard inverse-variance fixed effects meta-analysis methods. RESULTS: A total of 75 variants were genotyped/imputed successfully. Neither non-weighted nor weighted polygenic risk scores were associated with late radiation toxicity in individual studies (P>0.11) or after meta-analysis (P>0.24). No individual variant was associated with 2-year toxicity. CONCLUSION: Patients with a high polygenic susceptibility for prostate cancer have no increased risk for developing late radiotherapy toxicity. These findings suggest that patients with a genetic predisposition for prostate cancer, inferred by common variants, can be safely treated using current standard radiotherapy regimens. | |
dc.format | Print-Electronic | |
dc.format.extent | 1165 - 1174 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Prostatic Neoplasms | |
dc.subject | Radiation Injuries | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Germ-Line Mutation | |
dc.subject | Polymorphism, Single Nucleotide | |
dc.subject | Principal Component Analysis | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | European Continental Ancestry Group | |
dc.subject | Male | |
dc.subject | Genome-Wide Association Study | |
dc.title | Common genetic variation associated with increased susceptibility to prostate cancer does not increase risk of radiotherapy toxicity. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-03-08 | |
rioxxterms.versionofrecord | 10.1038/bjc.2016.94 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-05 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 10 | |
pubs.notes | No 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/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
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/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics | |
pubs.publication-status | Published | |
pubs.volume | 114 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | ICR-CTSU Urology and Head and Neck Trials Team | |
icr.researchteam | Clinical Academic Radiotherapy (Dearnaley) | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Dearnaley, David | |
dc.contributor.icrauthor | Hall, Emma | |
dc.contributor.icrauthor | Eeles, Rosalind | |