Association of Genomic Domains in and with Prostate Cancer Risk and Aggressiveness.

Authors:
Vivek L Patel Evan L Busch Tara M Friebel Angel Cronin Goska Leslie Lesley McGuffog Julian Adlard Simona Agata Bjarni A Agnarsson Munaza Ahmed Kristiina Aittomäki Elisa Alducci Irene L Andrulis Adalgeir Arason Norbert Arnold Grazia Artioli Brita Arver Bernd Auber Jacopo Azzollini Judith Balmaña Rosa B Barkardottir Daniel R Barnes Alicia Barroso Daniel Barrowdale Muriel Belotti Javier Benitez Birgitte Bertelsen Marinus J Blok Istvan Bodrogi Valérie Bonadona Bernardo Bonanni Davide Bondavalli Susanne E Boonen Julika Borde Ake Borg Angela R Bradbury Angela Brady Carole Brewer Joan Brunet Bruno Buecher Saundra S Buys Santiago Cabezas-Camarero Trinidad Caldés Almuth Caliebe Maria A Caligo Mariarosaria Calvello Ian G Campbell Ileana Carnevali Estela Carrasco Tsun L Chan Annie T W Chu Wendy K Chung Kathleen B M Claes Gemo Study Collaborators Embrace Collaborators Jackie Cook Laura Cortesi Fergus J Couch Mary B Daly Giuseppe Damante Esther Darder Rosemarie Davidson Miguel de la Hoya Lara Della Puppa Joe Dennis Orland Díez Yuan Chun Ding Nina Ditsch Susan M Domchek Alan Donaldson Bernd Dworniczak Douglas F Easton Diana M Eccles Rosalind A Eeles Hans Ehrencrona Bent Ejlertsen Christoph Engel D Gareth Evans Laurence Faivre Ulrike Faust Lídia Feliubadaló Lenka Foretova Florentia Fostira George Fountzilas Debra Frost Vanesa García-Barberán Pilar Garre Marion Gauthier-Villars Lajos Géczi Andrea Gehrig Anne-Marie Gerdes Paul Gesta Giuseppe Giannini Gord Glendon Andrew K Godwin David E Goldgar Mark H Greene Angelica M Gutierrez-Barrera Eric Hahnen Ute Hamann Jan Hauke Natalie Herold Frans B L Hogervorst Ellen Honisch John L Hopper Peter J Hulick KConFab Investigators Hebon Investigators Louise Izatt Agnes Jager Paul James Ramunas Janavicius Uffe Birk Jensen Thomas Dyrso Jensen Oskar Th Johannsson Esther M John Vijai Joseph Eunyoung Kang Karin Kast Johanna I Kiiski Sung-Won Kim Zisun Kim Kwang-Pil Ko Irene Konstantopoulou Gero Kramer Lotte Krogh Torben A Kruse Ava Kwong Mirjam Larsen Christine Lasset Charlotte Lautrup Conxi Lazaro Jihyoun Lee Jong Won Lee Min Hyuk Lee Johannes Lemke Fabienne Lesueur Annelie Liljegren Annika Lindblom Patricia Llovet Adria Lopez-Fernández Irene Lopez-Perolio Victor Lorca Jennifer T Loud Edmond S K Ma Phuong L Mai Siranoush Manoukian Veronique Mari Lynn Martin Laura Matricardi Noura Mebirouk Veronica Medici Hanne E J Meijers-Heijboer Alfons Meindl Arjen R Mensenkamp Clare Miller Denise Molina Gomes Marco Montagna Thea M Mooij Lidia Moserle Emmanuelle Mouret-Fourme Anna Marie Mulligan Katherine L Nathanson Marie Navratilova Heli Nevanlinna Dieter Niederacher Finn C Cilius Nielsen Liene Nikitina-Zake Kenneth Offit Edith Olah Olufunmilayo I Olopade Kai-Ren Ong Ana Osorio Claus-Eric Ott Domenico Palli Sue K Park Michael T Parsons Inge Sokilde Pedersen Bernard Peissel Ana Peixoto Pedro Pérez-Segura Paolo Peterlongo Annabeth Høgh Petersen Mary E Porteous Miguel Angel Pujana Paolo Radice Juliane Ramser Johanna Rantala Muhammad U Rashid Kerstin Rhiem Piera Rizzolo Mark E Robson Matti A Rookus Caroline M Rossing Kathryn J Ruddy Catarina Santos Claire Saule Rosa Scarpitta Rita K Schmutzler Hélène Schuster Leigha Senter Caroline M Seynaeve Payal D Shah Priyanka Sharma Vivian Y Shin Valentina Silvestri Jacques Simard Christian F Singer Anne-Bine Skytte Katie Snape Angela R Solano Penny Soucy Melissa C Southey Amanda B Spurdle Linda Steele Doris Steinemann Dominique Stoppa-Lyonnet Agostina Stradella Lone Sunde Christian Sutter Yen Y Tan Manuel R Teixeira Soo Hwang Teo Mads Thomassen Maria Grazia Tibiletti Marc Tischkowitz Silvia Tognazzo Amanda E Toland Stefania Tommasi Diana Torres Angela Toss Alison H Trainer Nadine Tung Christi J van Asperen Frederieke H van der Baan Lizet E van der Kolk Rob B van der Luijt Liselotte P van Hest Liliana Varesco Raymonda Varon-Mateeva Alessandra Viel Jeroen Vierstraete Roberta Villa Anna von Wachenfeldt Philipp Wagner Shan Wang-Gohrke Barbara Wappenschmidt Jeffrey N Weitzel Greet Wieme Siddhartha Yadav Drakoulis Yannoukakos Sook-Yee Yoon Cristina Zanzottera Kristin K Zorn Anthony V D'Amico Matthew L Freedman Mark M Pomerantz Georgia Chenevix-Trench Antonis C Antoniou Susan L Neuhausen Laura Ottini Henriette Roed Nielsen Timothy R Rebbeck

Cancer Res 2020 02 13;80(3):624-638. Epub 2019 Nov 13.

Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Pathogenic sequence variants (PSV) in or () are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 and 171 male PSV carriers with prostate cancer, and 3,388 and 2,880 male PSV carriers without prostate cancer. PSVs in the 3' region of (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; = 0.0002). No genotype-phenotype associations were detected for PSVs in . These results demonstrate that specific PSVs may be associated with elevated risk of developing aggressive prostate cancer. SIGNIFICANCE: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.

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http://dx.doi.org/10.1158/0008-5472.CAN-19-1840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553241PMC
February 2020
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