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dc.contributor.authorTurnbull, Cen_US
dc.contributor.authorSud, Aen_US
dc.contributor.authorHoulston, RSen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2018-09-03T08:40:44Z
dc.date.issued2018-09en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30158684en_US
dc.identifier10.1038/s41588-018-0202-0en_US
dc.identifier.citationNat Genet, 2018, 50 (9), pp. 1212 - 1218en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2500
dc.identifier.eissn1546-1718en_US
dc.identifier.doi10.1038/s41588-018-0202-0en_US
dc.description.abstractMore than 15 years have passed since the identification, through linkage, of 'first-wave' susceptibility genes for common cancers (BRCA1, BRCA2, MLH1 and MSH2). These genes have strong frequency-penetrance profiles, such that the associated clinical utility probably remains relevant regardless of the context of ascertainment. 'Second-wave' genes, not tractable by linkage, were subsequently identified by mutation screening of candidate genes (PALB2, ATM, CHEK2, BRIP1, RAD51C and RAD51D). Their innately weaker frequency-penetrance profiles have rendered delineation of cancer associations, risks and variant pathogenicity challenging, thereby compromising their clinical application. Early germline exome-sequencing endeavors for common cancers did not yield the long-anticipated slew of 'next-wave' genes but instead implied a highly polygenic genomic architecture requiring much larger experiments to make any substantive inroads into gene discovery. As such, the 'genetic economics' of frequency penetrance clearly indicates that focused identification of carriers of first-wave-gene mutations is most impactful for cancer control. With screening, prevention and early detection at the forefront of the cancer management agenda, we propose that the time is nigh for the initiation of national population-testing programs to identify carriers of first-wave gene mutation carriers. To fully deliver a precision prevention program, long-term, large-scale mutation studies that capture longitudinal clinical data and serial biosamples are required.en_US
dc.format.extent1212 - 1218en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.titleCancer genetics, precision prevention and a call to action.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-06-05en_US
rioxxterms.versionofrecord10.1038/s41588-018-0202-0en_US
rioxxterms.licenseref.startdate2018-09en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNat Geneten_US
pubs.issue9en_US
pubs.notesNot knownen_US
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/Molecular & Population Genetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Molecular & Population Genetics
pubs.publication-statusPublisheden_US
pubs.volume50en_US
pubs.embargo.termsNot knownen_US
icr.researchteamPredisposition & Translation Geneticsen_US
icr.researchteamMolecular & Population Geneticsen_US
dc.contributor.icrauthorHoulston, Richarden_US
dc.contributor.icrauthorTurnbull, Clare Annen_US
dc.contributor.icrauthorSud, Amiten_US
dc.contributor.icrauthorTurnbull, Clareen_US


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