dc.contributor.author | Brandão, A | |
dc.contributor.author | Paulo, P | |
dc.contributor.author | Maia, S | |
dc.contributor.author | Pinheiro, M | |
dc.contributor.author | Peixoto, A | |
dc.contributor.author | Cardoso, M | |
dc.contributor.author | Silva, MP | |
dc.contributor.author | Santos, C | |
dc.contributor.author | Eeles, RA | |
dc.contributor.author | Kote-Jarai, Z | |
dc.contributor.author | Muir, K | |
dc.contributor.author | Ukgpcs Collaborators, | |
dc.contributor.author | Schleutker, J | |
dc.contributor.author | Wang, Y | |
dc.contributor.author | Pashayan, N | |
dc.contributor.author | Batra, J | |
dc.contributor.author | Apcb BioResource, | |
dc.contributor.author | Grönberg, H | |
dc.contributor.author | Neal, DE | |
dc.contributor.author | Nordestgaard, BG | |
dc.contributor.author | Tangen, CM | |
dc.contributor.author | Southey, MC | |
dc.contributor.author | Wolk, A | |
dc.contributor.author | Albanes, D | |
dc.contributor.author | Haiman, CA | |
dc.contributor.author | Travis, RC | |
dc.contributor.author | Stanford, JL | |
dc.contributor.author | Mucci, LA | |
dc.contributor.author | West, CML | |
dc.contributor.author | Nielsen, SF | |
dc.contributor.author | Kibel, AS | |
dc.contributor.author | Cussenot, O | |
dc.contributor.author | Berndt, SI | |
dc.contributor.author | Koutros, S | |
dc.contributor.author | Sørensen, KD | |
dc.contributor.author | Cybulski, C | |
dc.contributor.author | Grindedal, EM | |
dc.contributor.author | Park, JY | |
dc.contributor.author | Ingles, SA | |
dc.contributor.author | Maier, C | |
dc.contributor.author | Hamilton, RJ | |
dc.contributor.author | Rosenstein, BS | |
dc.contributor.author | Vega, A | |
dc.contributor.author | The Impact Study Steering Committee And Collaborators, | |
dc.contributor.author | Kogevinas, M | |
dc.contributor.author | Wiklund, F | |
dc.contributor.author | Penney, KL | |
dc.contributor.author | Brenner, H | |
dc.contributor.author | John, EM | |
dc.contributor.author | Kaneva, R | |
dc.contributor.author | Logothetis, CJ | |
dc.contributor.author | Neuhausen, SL | |
dc.contributor.author | Ruyck, KD | |
dc.contributor.author | Razack, A | |
dc.contributor.author | Newcomb, LF | |
dc.contributor.author | Canary Pass Investigators, | |
dc.contributor.author | Lessel, D | |
dc.contributor.author | Usmani, N | |
dc.contributor.author | Claessens, F | |
dc.contributor.author | Gago-Dominguez, M | |
dc.contributor.author | Townsend, PA | |
dc.contributor.author | Roobol, MJ | |
dc.contributor.author | The Profile Study Steering Committee, | |
dc.contributor.author | The Practical Consortium, | |
dc.contributor.author | Teixeira, MR | |
dc.date.accessioned | 2021-01-18T14:38:53Z | |
dc.date.issued | 2020-11-04 | |
dc.identifier.citation | Cancers, 2020, 12 (11) | |
dc.identifier.issn | 2072-6694 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4296 | |
dc.identifier.eissn | 2072-6694 | |
dc.identifier.doi | 10.3390/cancers12113254 | |
dc.description.abstract | The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families. | |
dc.format | Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | MDPI | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-10-20 | |
rioxxterms.versionofrecord | 10.3390/cancers12113254 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-11-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancers | |
pubs.issue | 11 | |
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/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-status | Published | |
pubs.volume | 12 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Oncogenetics | |
dc.contributor.icrauthor | Eeles, Rosalind | |
dc.contributor.icrauthor | Kote-Jarai, Zsofia | |