dc.contributor.author | Litchfield, K | |
dc.contributor.author | Loveday, C | |
dc.contributor.author | Levy, M | |
dc.contributor.author | Dudakia, D | |
dc.contributor.author | Rapley, E | |
dc.contributor.author | Nsengimana, J | |
dc.contributor.author | Bishop, DT | |
dc.contributor.author | Reid, A | |
dc.contributor.author | Huddart, R | |
dc.contributor.author | Broderick, P | |
dc.contributor.author | Houlston, RS | |
dc.contributor.author | Turnbull, C | |
dc.date.accessioned | 2018-03-28T15:20:51Z | |
dc.date.issued | 2018-06 | |
dc.identifier.citation | European urology, 2018, 73 (6), pp. 828 - 831 | |
dc.identifier.issn | 0302-2838 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1622 | |
dc.identifier.eissn | 1873-7560 | |
dc.identifier.doi | 10.1016/j.eururo.2018.01.021 | |
dc.description.abstract | Testicular 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.format | Print-Electronic | |
dc.format.extent | 828 - 831 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Neoplasms, Germ Cell and Embryonal | |
dc.subject | Testicular Neoplasms | |
dc.subject | Genetic Predisposition to Disease | |
dc.subject | Risk Factors | |
dc.subject | Case-Control Studies | |
dc.subject | Gene Frequency | |
dc.subject | Penetrance | |
dc.subject | Mutation | |
dc.subject | Male | |
dc.subject | Whole Exome Sequencing | |
dc.title | Large-scale Sequencing of Testicular Germ Cell Tumour (TGCT) Cases Excludes Major TGCT Predisposition Gene. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-01-22 | |
rioxxterms.versionofrecord | 10.1016/j.eururo.2018.01.021 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/under-embargo-all-rights-reserved | |
rioxxterms.licenseref.startdate | 2018-06 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | European urology | |
pubs.issue | 6 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 73 | en_US |
pubs.embargo.terms | Not known | |
icr.researchteam | Predisposition & Translation Genetics | en_US |
icr.researchteam | Cancer Genomics | en_US |
icr.researchteam | Molecular & Population Genetics | en_US |
icr.researchteam | Clinical Academic Radiotherapy (Huddart) | en_US |
dc.contributor.icrauthor | Turnbull, Clare Ann | |
dc.contributor.icrauthor | Houlston, Richard | |
dc.contributor.icrauthor | Huddart, Robert | |
dc.contributor.icrauthor | Turnbull, Clare | |
dc.contributor.icrauthor | Broderick, Peter | |
dc.contributor.icrauthor | Litchfield, Kevin | |