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Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness
Cancer Res. 2020 Feb 1;80(3) :624-638
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Abstract
Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer (PCa). We evaluated whether PSVs in BRCA1/2 were associated with risk of overall PCa or high grade (Gleason 8+) PCa using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with PCa, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without PCa. PSVs in the 3' region of BRCA2 (c.7914+) were significantly associated with elevated risk of PCa compared with reference bin c.1001-c.7913 (HR=1.78, 95%CI: 1.25-2.52, p=0.001), as well as elevated risk of Gleason 8+ PCa (HR=3.11, 95%CI: 1.63-5.95, p=0.001). c.756-c.1000 was also associated with elevated PCa risk (HR=2.83, 95%CI: 1.71-4.68, p=0.00004) and elevated risk of Gleason 8+ PCa (HR=4.95, 95%CI: 2.12-11.54, p=0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive PCa.
Notes
1538-7445 Patel, Vivek L Busch, Evan L Friebel, Tara M Cronin, Angel Leslie, Goska ORCID: https://orcid.org/0000-0001-5756-6222 McGuffog, Lesley Adlard, Julian ORCID: https://orcid.org/0000-0002-1693-0435 Agata, Simona Agnarsson, Bjarni A Ahmed, Munaza Aittomaki, Kristiina Alducci, Elisa Andrulis, Irene L Arason, Adalgeir Arnold, Norbert ORCID: https://orcid.org/0000-0003-4523-8808 Artioli, Grazia Arver, Brita Auber, Bernd ORCID: https://orcid.org/0000-0003-1880-291X Azzollini, Jacopo ORCID: https://orcid.org/0000-0002-9364-9778 Balmana, Judith Barkardottir, Rosa B Barnes, Daniel R ORCID: https://orcid.org/0000-0002-3781-7570 Barroso, Alicia Barrowdale, Daniel Belotti, Muriel Benitez, Javier Bertelsen, Brigitte Blok, Marinus J Bodrogi, Istvan Bonadona, Valerie Bonanni, Bernardo Bondavalli, Davide Boonen, Susanne E Borde, Julika Borg, Ake Bradbury, Angela R Brady, Angela Brewer, Carole Brunet, Joan ORCID: https://orcid.org/0000-0003-1945-3512 Buecher, Bruno Buys, Saundra S 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https://orcid.org/0000-0001-8761-714X Engel, Christoph Evans, D Gareth ORCID: https://orcid.org/0000-0002-8482-5784 Faivre, Laurence Faust, Ulrike Feliubadalo, Lidia Foretova, Lenka Fostira, Florentia Fountzilas, George Frost, Debra Garcia-Barberan, Vanesa Garre, Pilar ORCID: https://orcid.org/0000-0001-8285-4138 Gauthier-Villars, Marion Geczi, Lajos Gehrig, Andrea Gerdes, Anne-Marie Gesta, Paul Giannini, Giuseppe Glendon, Gord Godwin, Andrew K Goldgar, David E Greene, Mark H ORCID: https://orcid.org/0000-0003-1852-9239 Gutierrez-Barrera, Angelica M Hahnen, Eric Hamann, Ute Hauke, Jan Herold, Natalie Hogervorst, Frans B L Honisch, Ellen Hopper, John L Hulick, Peter J ORCID: https://orcid.org/0000-0001-8397-4078 Investigators, kConFab Investigators, Hebon Izatt, Louise Jager, Agnes ORCID: https://orcid.org/0000-0002-7713-1450 James, Paul ORCID: https://orcid.org/0000-0002-4361-4657 Janavicius, Ramunas Jensen, Uffe Birk Jensen, Thomas Dyrso Johannsson, Oskar Th John, Esther M ORCID: 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