Henriette Roed Nielsen1, Janne Petersen2,3, Christina Therkildsen2, Anne-Bine Skytte4, Mef Nilbert2,5. 1. a Department of Clinical Genetics , Vejle Hospital , Denmark. 2. b HNPCC Register, Clinical Research Center, Copenhagen University Hospital , Hvidovre , Denmark. 3. c Department of Biostatistics , University of Copenhagen , Denmark. 4. d Department of Clinical Genetics , Aarhus University Hospital , Denmark. 5. e Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University , Lund , Sweden.
Abstract
BACKGROUND: The risk of cancer in men from BRCA1 and BRCA2 families is relevant to define to motivate genetic testing and optimize recommendations for surveillance. MATERIAL AND METHODS: We assessed the risk of cancer in male mutation carriers and their first-degree relatives in 290 BRCA1 and BRCA2 families with comparison to matched controls with the aim to motivate genetic testing and optimize recommendations for surveillance. RESULTS: Mutation carriers in BRCA1 families were not at increased risk of cancer, whereas mutation carriers in BRCA2 families were at increased risk of male breast cancer and prostate cancer with cumulative risks of 12.5% and 18.8%, respectively. Breast cancer developed at a mean age of 59 years, typically as ER/PR positive ductal carcinomas. Prostate cancer developed at a mean age of 68 years, with Gleason scores ≥ 8 in 40% of the tumors. The hazard ratio for BRCA2-associated prostate cancer was 3.7 (p < 0.001) in mutation carriers and 3.1 (p = 0.001) in first-degree relatives. Of the 37 prostate cancers, 19 were linked to four BRCA2 mutations within a region defined by c.6373-c.6492. Individuals with mutations herein had a HR of 3.7 for prostate cancer compared to individuals with mutations outside of this region. CONCLUSIONS: Male mutation carriers and first-degree relatives in BRCA2 families are at an increased risk of breast cancer and prostate cancer with a potential prostate cancer cluster region within exon 11 of BRCA2.
BACKGROUND: The risk of cancer in men from BRCA1 and BRCA2 families is relevant to define to motivate genetic testing and optimize recommendations for surveillance. MATERIAL AND METHODS: We assessed the risk of cancer in male mutation carriers and their first-degree relatives in 290 BRCA1 and BRCA2 families with comparison to matched controls with the aim to motivate genetic testing and optimize recommendations for surveillance. RESULTS: Mutation carriers in BRCA1 families were not at increased risk of cancer, whereas mutation carriers in BRCA2 families were at increased risk of male breast cancer and prostate cancer with cumulative risks of 12.5% and 18.8%, respectively. Breast cancer developed at a mean age of 59 years, typically as ER/PR positive ductal carcinomas. Prostate cancer developed at a mean age of 68 years, with Gleason scores ≥ 8 in 40% of the tumors. The hazard ratio for BRCA2-associated prostate cancer was 3.7 (p < 0.001) in mutation carriers and 3.1 (p = 0.001) in first-degree relatives. Of the 37 prostate cancers, 19 were linked to four BRCA2 mutations within a region defined by c.6373-c.6492. Individuals with mutations herein had a HR of 3.7 for prostate cancer compared to individuals with mutations outside of this region. CONCLUSIONS: Male mutation carriers and first-degree relatives in BRCA2 families are at an increased risk of breast cancer and prostate cancer with a potential prostate cancer cluster region within exon 11 of BRCA2.
Authors: Shuai Li; Valentina Silvestri; Goska Leslie; Timothy R Rebbeck; Susan L Neuhausen; John L Hopper; Henriette Roed Nielsen; Andrew Lee; Xin Yang; Lesley McGuffog; Michael T Parsons; Irene L Andrulis; Norbert Arnold; Muriel Belotti; Åke Borg; Bruno Buecher; Saundra S Buys; Sandrine M Caputo; Wendy K Chung; Chrystelle Colas; Sarah V Colonna; Jackie Cook; Mary B Daly; Miguel de la Hoya; Antoine de Pauw; Hélène Delhomelle; Jacqueline Eason; Christoph Engel; D Gareth Evans; Ulrike Faust; Tanja N Fehm; Florentia Fostira; George Fountzilas; Megan Frone; Vanesa Garcia-Barberan; Pilar Garre; Marion Gauthier-Villars; Andrea Gehrig; Gord Glendon; David E Goldgar; Lisa Golmard; Mark H Greene; Eric Hahnen; Ute Hamann; Helen Hanson; Tiara Hassan; Julia Hentschel; Judit Horvath; Louise Izatt; Ramunas Janavicius; Yue Jiao; Esther M John; Beth Y Karlan; Sung-Won Kim; Irene Konstantopoulou; Ava Kwong; Anthony Laugé; Jong Won Lee; Fabienne Lesueur; Noura Mebirouk; Alfons Meindl; Emmanuelle Mouret-Fourme; Hannah Musgrave; Joanne Ngeow Yuen Yie; Dieter Niederacher; Sue K Park; Inge Sokilde Pedersen; Juliane Ramser; Susan J Ramus; Johanna Rantala; Muhammad U Rashid; Florian Reichl; Julia Ritter; Andreas Rump; Marta Santamariña; Claire Saule; Gunnar Schmidt; Rita K Schmutzler; Leigha Senter; Saba Shariff; Christian F Singer; Melissa C Southey; Dominique Stoppa-Lyonnet; Christian Sutter; Yen Tan; Soo Hwang Teo; Mary Beth Terry; Mads Thomassen; Marc Tischkowitz; Amanda E Toland; Diana Torres; Ana Vega; Sebastian A Wagner; Shan Wang-Gohrke; Barbara Wappenschmidt; Bernhard H F Weber; Drakoulis Yannoukakos; Amanda B Spurdle; Douglas F Easton; Georgia Chenevix-Trench; Laura Ottini; Antonis C Antoniou Journal: J Clin Oncol Date: 2022-01-25 Impact factor: 50.717
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 Journal: Cancer Res Date: 2019-11-13 Impact factor: 13.312
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