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dc.contributor.authorDarst, BF
dc.contributor.authorSheng, X
dc.contributor.authorEeles, RA
dc.contributor.authorKote-Jarai, Z
dc.contributor.authorConti, DV
dc.contributor.authorHaiman, CA
dc.date.accessioned2021-08-20T14:52:03Z
dc.date.available2021-08-20T14:52:03Z
dc.identifier.citationEuropean urology, 2021, 80 (2), pp. 134 - 138
dc.identifier.issn0302-2838
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4771
dc.identifier.eissn1873-7560
dc.identifier.eissn1873-7560en_US
dc.identifier.doi10.1016/j.eururo.2021.04.013
dc.identifier.doi10.1016/j.eururo.2021.04.013en_US
dc.description.abstractAlthough prostate cancer is known to have a strong genetic basis and is influenced by both common and rare variants, the ability to investigate the combined effect of such genetic risk factors has been limited to date. We conducted an investigation of 81 094 men from the UK Biobank, including 3568 prostate cancer cases, to examine the combined effect of rare pathogenic/likely pathogenic/deleterious (P/LP/D) germline variants and common prostate cancer risk variants, measured using a polygenic risk score (PRS), on prostate cancer risk. The absolute risk of prostate cancer for HOXB13, BRCA2, ATM, and CHEK2 P/LP/D carriers ranged from 9% to 56%, and the absolute risk in noncarriers ranged from 2% to 31%, by age 85 yr, for men in the lowest and highest PRS decile, respectively. The high-penetrant HOXB13 G84E prostate cancer risk variant was most common in cases in the lowest PRS quintile (4.4%) and least common in cases in the highest PRS quintile (0.5%; p = 0.005), whereas there was no statistically significant difference in frequencies by PRS in controls. While rare and common variants strongly and distinctly influence prostate cancer onset, consideration of rare and common variants in conjunction will lead to more precise estimates of a man's lifetime risk of prostate cancer. PATIENT SUMMARY: We found that the risk of prostate cancer conveyed by rare variants could vary depending on an individual's genetic profile of common risk variants. This implies that in order to comprehensively assess genetic risk of prostate cancer, it is important to consider both rare and common variants.
dc.formatPrint-Electronic
dc.format.extent134 - 138
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleCombined Effect of a Polygenic Risk Score and Rare Genetic Variants on Prostate Cancer Risk.
dc.typeJournal Article
dcterms.dateAccepted2021-04-12
rioxxterms.versionAM
rioxxterms.versionofrecord10.1016/j.eururo.2021.04.013
dc.relation.isPartOfEuropean urology
pubs.issue2
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/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/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-statusPublished
pubs.volume80en_US
pubs.embargo.termsNot known
icr.researchteamOncogenetics
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorKote-Jarai, Zsofiaen
dc.contributor.icrauthorEeles, Rosalinden


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