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dc.contributor.authorLitchfield, K
dc.contributor.authorLoveday, C
dc.contributor.authorLevy, M
dc.contributor.authorDudakia, D
dc.contributor.authorRapley, E
dc.contributor.authorNsengimana, J
dc.contributor.authorBishop, DT
dc.contributor.authorReid, A
dc.contributor.authorHuddart, R
dc.contributor.authorBroderick, P
dc.contributor.authorHoulston, RS
dc.contributor.authorTurnbull, C
dc.date.accessioned2018-03-28T15:20:51Z
dc.date.issued2018-06
dc.identifier.citationEuropean urology, 2018, 73 (6), pp. 828 - 831
dc.identifier.issn0302-2838
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1622
dc.identifier.eissn1873-7560
dc.identifier.doi10.1016/j.eururo.2018.01.021
dc.description.abstractTesticular germ cell tumour (TGCT), the most common cancer in young men, has a significant heritable basis that has long raised questions as to the existence of underlying major high-penetrance susceptibility gene(s). To determine the contribution of rare gene mutations to the inherited risk of TGCT, we analysed germline whole-exome data for 919 TGCT cases and 1609 cancer-free controls. We compared frequencies between TGCT cases and controls of rare (<1%) and low-frequency (1-5%) coding variants (1) individually and (2) collapsed at the gene level via burden testing (T1, disruptive; T2, all deleterious; and T3, all nonsynonymous) using Fisher's exact test with Bonferroni correction of significance thresholds. No individual variant or individual gene showed a significant association with TGCT after correction for multiple testing. In the largest whole-exome sequencing study of testicular cancer reported to date, our findings do not support the existence of a major high-penetrance TGCT susceptibility gene (of odds ratio >10 and allele frequency [combined]>0.01%). Owing to its power, this study cannot exclude the existence of susceptibility genes responsible for occasional TGCT families or of rare mutations that confer very modest relative risks. In concert with findings from genome-wide association studies, our data support the notion that inherited susceptibility is largely polygenic with substantial contribution from common variation. PATIENT SUMMARY:In the largest study of its kind, we sequenced ∼20 000 genes in 919 men with testicular germ cell tumour (TGCT) and 1609 TGCT-free individuals and found no evidence of a single major gene underlying predisposition to TGCT (in the manner of BRCA1 for breast cancer). Instead, familial risk of TGCT is likely to be due to varying dosages of hundreds of minor genetic factors.
dc.formatPrint-Electronic
dc.format.extent828 - 831
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.subjectHumans
dc.subjectNeoplasms, Germ Cell and Embryonal
dc.subjectTesticular Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectRisk Factors
dc.subjectCase-Control Studies
dc.subjectGene Frequency
dc.subjectPenetrance
dc.subjectMutation
dc.subjectMale
dc.subjectWhole Exome Sequencing
dc.titleLarge-scale Sequencing of Testicular Germ Cell Tumour (TGCT) Cases Excludes Major TGCT Predisposition Gene.
dc.typeJournal Article
dcterms.dateAccepted2018-01-22
rioxxterms.versionofrecord10.1016/j.eururo.2018.01.021
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2018-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfEuropean urology
pubs.issue6
pubs.notesNot known
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Predisposition & Translation Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart)
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/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Predisposition & Translation Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Clinical Academic Radiotherapy (Huddart)
pubs.publication-statusPublished
pubs.volume73en_US
pubs.embargo.termsNot known
icr.researchteamPredisposition & Translation Geneticsen_US
icr.researchteamCancer Genomicsen_US
icr.researchteamMolecular & Population Geneticsen_US
icr.researchteamClinical Academic Radiotherapy (Huddart)en_US
dc.contributor.icrauthorTurnbull, Clare Annen
dc.contributor.icrauthorHoulston, Richarden
dc.contributor.icrauthorHuddart, Roberten
dc.contributor.icrauthorTurnbull, Clareen
dc.contributor.icrauthorBroderick, Peteren
dc.contributor.icrauthorLitchfield, Kevinen


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