{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:52:21Z","timestamp":1772211141218,"version":"3.50.1"},"reference-count":66,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T00:00:00Z","timestamp":1604448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"IPO-Porto Research Center","award":["CI-IPOP-16-2012"],"award-info":[{"award-number":["CI-IPOP-16-2012"]}]},{"name":"Canadian Institutes of Health Research, European Commission\u2019s Seventh Framework Programme","award":["HEALTH-F2-2009-223175"],"award-info":[{"award-number":["HEALTH-F2-2009-223175"]}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C5047\/A7357, C1287\/A10118, C1287\/A16563, C5047\/A3354, C5047\/A10692, C16913\/A6135"],"award-info":[{"award-number":["C5047\/A7357, C1287\/A10118, C1287\/A16563, C5047\/A3354, C5047\/A10692, C16913\/A6135"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A8197\/A16565"],"award-info":[{"award-number":["A8197\/A16565"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative","award":["No. 1 U19 CA 148537-01"],"award-info":[{"award-number":["No. 1 U19 CA 148537-01"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 CA 148537, X01HG007492"],"award-info":[{"award-number":["U19 CA 148537, X01HG007492"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NCI U01 CA188392"],"award-info":[{"award-number":["NCI U01 CA188392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PEst-OE\/SAU\/ UI0776\/2014, PTDC\/DTP-PIC\/1308\/2014, UID\/DTP\/00776\/2013\/POCI-01-0145-FEDER-006868, SFRH\/BD\/71397\/2010, SFRH\/BD\/73719\/2010"],"award-info":[{"award-number":["PEst-OE\/SAU\/ UI0776\/2014, PTDC\/DTP-PIC\/1308\/2014, UID\/DTP\/00776\/2013\/POCI-01-0145-FEDER-006868, SFRH\/BD\/71397\/2010, SFRH\/BD\/73719\/2010"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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&gt;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\u2013control 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&gt;G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1\u20133.2). 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&gt;G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.<\/jats:p>","DOI":"10.3390\/cancers12113254","type":"journal-article","created":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:37Z","timestamp":1604534437000},"page":"3254","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["The CHEK2 Variant C.349A&gt;G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0938-1543","authenticated-orcid":false,"given":"Andreia","family":"Brand\u00e3o","sequence":"first","affiliation":[{"name":"Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Paula","family":"Paulo","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Sofia","family":"Maia","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Manuela","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Ana","family":"Peixoto","sequence":"additional","affiliation":[{"name":"Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Marta","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Maria P.","family":"Silva","sequence":"additional","affiliation":[{"name":"Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"given":"Catarina","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3698-6241","authenticated-orcid":false,"given":"Rosalind A.","family":"Eeles","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research, London SM2 5NG, UK"},{"name":"Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK"}]},{"given":"Zsofia","family":"Kote-Jarai","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research, London SM2 5NG, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6429-988X","authenticated-orcid":false,"given":"Kenneth","family":"Muir","sequence":"additional","affiliation":[{"name":"Division of Population Health, Health Services Research and Primary Care, University of Manchester, Oxford Road, Manchester M13 9PL, UK"},{"name":"Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK"}]},{"name":"UKGPCS Collaborators","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1863-0305","authenticated-orcid":false,"given":"Johanna","family":"Schleutker","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, University of Turku, FI-20014 Turun Yliopisto, 20050 Turku, Finland"},{"name":"Department of Medical Genetics, Genomics, Laboratory Division, Turku University Hospital, P.O. 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Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA"}]},{"given":"Susan L.","family":"Neuhausen","sequence":"additional","affiliation":[{"name":"Department of Population Sciences, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA"}]},{"given":"Kim De","family":"Ruyck","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Sciences, Basic Medical Sciences, Ghent University, Proeftuinstraat 86, 9000 Gent, Belgium"}]},{"given":"Azad","family":"Razack","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia"}]},{"given":"Lisa F.","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, DC 98109-1024, USA"},{"name":"Department of Urology, University of Washington, 1959 NE Pacific Street, Box 356510, Seattle, WA 98195, USA"}]},{"name":"Canary PASS Investigators","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-244X","authenticated-orcid":false,"given":"Davor","family":"Lessel","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany"}]},{"given":"Nawaid","family":"Usmani","sequence":"additional","affiliation":[{"name":"Department of Oncology, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada"},{"name":"Division of Radiation Oncology, Cross Cancer Institute, 11560 University Avenue, Edmonton, AB T6G 1Z2, Canada"}]},{"given":"Frank","family":"Claessens","sequence":"additional","affiliation":[{"name":"Molecular Endocrinology Laboratory, Department of Cellular and Molecular Medicine, Campus Gasthuisberg, University of Leuven, Herestraat 49, P.O. 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