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dc.contributor.authorTurnbull, C
dc.contributor.authorSud, A
dc.contributor.authorHoulston, RS
dc.date.accessioned2018-09-03T08:40:44Z
dc.date.issued2018-09
dc.identifier.citationNature genetics, 2018, 50 (9), pp. 1212 - 1218
dc.identifier.issn1061-4036
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2500
dc.identifier.eissn1546-1718
dc.identifier.doi10.1038/s41588-018-0202-0
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.
dc.formatPrint-Electronic
dc.format.extent1212 - 1218
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleCancer genetics, precision prevention and a call to action.
dc.typeJournal Article
dcterms.dateAccepted2018-06-05
rioxxterms.versionofrecord10.1038/s41588-018-0202-0
rioxxterms.licenseref.urihttps://www.rioxx.net/licenses/under-embargo-all-rights-reserved
rioxxterms.licenseref.startdate2018-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature genetics
pubs.issue9
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
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.publication-statusPublished
pubs.volume50
pubs.embargo.termsNot known
icr.researchteamPredisposition & Translation Geneticsen_US
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorTurnbull, Clare Annen
dc.contributor.icrauthorSud, Amiten
dc.contributor.icrauthorTurnbull, Clareen
dc.contributor.icrauthorHoulston, Richarden


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