Citations 14
Germline Pathogenic DROSHA Variants Are Linked to Pineoblastoma and Wilms Tumor Predisposition
Fiorica, Peter N. , Golmard, Lisa , Kim, Jung , Bao, Riyue , Lin, Frank Y. , Roy, Angshumoy , Pribnow, Allison , Perrino, Melissa R. , Masliah‐Planchon, Julien , Michalak-Provost, Sophie , Wong, Jennifer , Filser, Mathilde , Bourdeaut, Franck , Brahimi, Afane, Ingster, Olivier, Jackson, Sarah A. , Sasaki, Mark M. , Fowler, Trent, Ng, Anita , Corbett, Ryan J. , Kaufman, Rebecca , Haley, Jeremy S. , Carey, David J. , Huang, Kuan‐lin , Diskin, Sharon J. , Al‐Kateb, Hussam , Schultz, Kris Ann P. , Onel, Kenan , Stoppa-Lyonnet, Dominique , Bourdeaut, Franck , Brahimi, Afane , Ingster, Olivier , Saulnier Sholler, Giselle , Jackson, Sarah A , Sasaki, Mark M , Fowler, Trent , Ng, Anita , Corbett, Ryan J , Kaufman, Rebecca S , Haley, Jeremy S , Carey, David J , Huang, Kuan-Lin , Diskin, Sharon J , Rokita, Jo Lynne , Al-Kateb, Hussam , McGee, Rose B , Schiffman, Joshua D , Chen, Kenneth S , Stewart, Douglas R , Parsons, D Williams , Plon, Sharon E. , Schultz, Kris Ann P , Onel, Kenan , Perrino, Melissa R , Lin, Frank Y , Stoppa‐Lyonnet, Dominique , Rokita, Jo Lynne , Chen, Kenneth , Parsons, D. Williams
Clinical Cancer Research | February 24, 2025 | Volume: 31 | Issue: 8 | Pages: 1491-1503
Abstract Purpose: DROSHA, DGCR8, and DICER1 regulate miRNA biogenesis and are commonly mutated in cancer. Although DGCR8 and DICER1 germline pathogenic variants (GPV) cause autosomal dominant tumor predisposition, no association between DROSHA GPVs and clinical phenotypes has been reported. Experimental Design: After obtaining informed consent, sequencing was performed on germline and tumor samples from all patients. The occurrence of germline DROSHA GPVs was investigated in large pediatric and adult cancer datasets. The population prevalence of DROSHA GPVs was investigated in the UK Biobank and Geisinger DiscovEHR cohorts. Results: We describe nine children from eight families with heterozygous DROSHA GPVs and a diagnosis of pineoblastoma (n = 8) or Wilms tumor (n = 1). A somatic second hit in DROSHA was detected in all eight tumors analyzed. All pineoblastoma tumors analyzed were classified as miRNA processing–altered 1 subtype. We estimate the population prevalence of germline DROSHA loss-of-function variants to be 1:3,875 to 1:4,843 but find no evidence for increased adult cancer risk. Conclusions: This is the first report of DROSHA-related tumor predisposition. As pineoblastoma and Wilms tumor are also associated with DICER1 GPVs, our results suggest that the tissues of origin for these tumors are uniquely tolerant of general miRNA loss. The miRNA processing–altered 1 pineoblastoma subtype is associated with older age of diagnosis and better outcomes than other subtypes, suggesting DROSHA GPV status may have important clinical and prognostic significance. We suggest that genetic testing for DROSHA GPVs be considered for patients with pineoblastoma, Wilms tumor, or other DICER1-/DGCR8-related conditions and propose surveillance recommendations through research studies for individuals with DROSHA GPVs.
A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2
Zanti, Maria , O'Mahony, Denise G , Li, Hongyan , Aittomäkkiki, Kristiina, Andrulis, Irene L. , Aronson, Kristan J. , Bolla, Manjeet K. , Brenner, Hermann , Caputo, Sandrine M. , Chang‐Claude, Jenny , Collaborators, GC-HBOC study, Daly, Mary B., Nicolo, Arcangela De , Eccles, Diana M., Engel, Christoph , Evans, D. Gareth , Fasching, Peter A. , Giele, Willemina R. R. Geurts -, Glendon, Gord , Goldberg, Mark S. , Gómez, E. , Güendert, Melanie, Hahnen, Eric , Haiman, Christopher A. , Hamann, Ute, Harkness, Elaine F. , Hogervorst, Frans B.L., Hoppe, Reiner , Houdayer, Claude , Houlston, Richard S. , Howell, Anthony , Investigators, ABCTB, Jakimovska, Milena , John, Esther M. , Kristensen, Vessela N. , Lambrechts, Diether , Léone, Mélanie, Lindblom, Annika , Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush , Menon, Usha , Offit, Kenneth, Park, Sue K. , Peto, Julian , Plaseska‐Karanfilska, Dijana , Romero, Atocha , Schmutzler, Rita K. , Stone, Jennifer , Tapper, William , Teo, Soo‐Hwang , Thomassen, Mads , Vachon, Celine M. , Vega, Ana , Wang, Qin , Wappenschmidt, Barbara , Zheng, Wei , Easton, Douglas F. , Goldgar, David E., Eccles, Diana , Lambrechts, Diether , Houdayer, Claude , Lambrechts, Diether , Teo, Soo H , Eccles, Diana , Menon, Usha , Houlston, Richard S , Vega, Ana , Evans, D Gareth , John, Esther M , Lambrechts, Diether , Brenner, Hermann , Romero, Atocha , Engel, Christoph , Zheng, Wei , Stone, Jennifer , Gómez-García, Encarna B , De Nicolo, Arcangela , Manoukian, Siranoush , Lindblom, Annika , Plaseska-Karanfilska, Dijana , Parsons, Michael T. , Dennis, Joe , Anton‐Culver, Hoda , Augustinsson, Annelie , Becher, Heiko , Bojesen, Stig E. , Brown, Melissa A. , Buys, Saundra S. , Canzian, Federico , Castelao, Jose E. , Czene, Kamila , Devilee, Peter , Dörk, Thilo , Dunning, Alison M. , Dwek, Miriam , Gago-Domínguez, Manuela , García‐Closas, Montserrat , García-Sáenz, José Á. , Gentry‐Maharaj, Aleksandra , Geurts-Giele, Willemina R.R. , Giles, Graham G. , Guénel, Pascal , Hall, Per N , Hollestelle, Antoinette , Hopper, John L. , Jakubowska, Anna , Jernström, Helena , Kaaks, Rudolf , Kitahara, Cari M. , Koutros, Stella , Kraft, Peter , Lacey, James V. , Léoné, Mélanie, Lubiński, Jan , Lush, Michael J. , Mannermaa, Arto, Margolin, Sara , Martı́nez, Marı́a Elena , Milne, Roger L. , Monteiro, Álvaro N.A. , Murphy, Rachel A. , Neuhausen, Susan L. , Nevanlinna, Heli , Newman, William G. , James, Paul A. , Peterlongo, Paolo , Punie, Kevin , Radice, Paolo , Rashid, Muhammad Usman , Rennert, Gad , Rosenberg, Efraim H. , Saloustros, Emmanouil , Sandler, Dale P. , Schmidt, Marjanka K. , Shu, Xiao‐Ou , Simard, Jacques , Southey, Melissa C. , Stoppa‐Lyonnet, Dominique , Tamimi, Rulla M. , Taylor, Jack A. , Teras, Lauren R. , Terry, Mary Beth , Troester, Melissa A. , Vachon, Celine M. , Vreeswijk, Maaike P.G. , Weinberg, Clarice R. , Wolk, Alicja , Feng, Bing , Couch, Fergus J. , Spurdle, Amanda B. , Michailidou, Kyriaki
Human Mutation | September 15, 2023 | Volume: 2023 | Issue: No issue available | Pages: 1-17
A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity—findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Breast and Prostate Cancer Risks for MaleBRCA1andBRCA2Pathogenic Variant Carriers Using Polygenic Risk Scores
Barnes, Daniel R. , Silvestri, Valentina , Leslie, Goska , McGuffog, Lesley, Yang, Xin , Adlard, Julian , Agnarsson, Bjarni A. , Ahmed, Munaza, Aittomäki, Kristiina, Andrulis, Irene L. , Arason, Aðalgeir , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barrowdale, Daniel , Belotti, Muriel, Berthet, Pascaline, Boonen, Susanne E. , Borg, Åke , Brady, Angela F., Brewer, Carole, Brunet, Joan , Bucalo, Agostino, Caldés, Trinidad , Cassingham, Hayley , Christensen, Lise Lotte , Cini, Giulia , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Cortesi, Laura , Damante, Giuseppe , Darder, Esther , Davidson, Rosemarie, Leeneer, Kim De , Putter, Robin De , Valle, Jesús Del , Ding, Yuan Chun , Donaldson, Alan , Eason, Jacqueline , Eeles, Rosalind A. , Engel, Christoph , Evans, D. Gareth , Feliubadaló, Lídia , Frone, Megan N. , Frost, Debra, Gehrig, Andrea, Giraud, Sophie , Glendon, Gord , Goldgar, David E. , Greene, Mark H. , Gregory, Helen , Groß, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas van Overeem , Hanson, Helen , Horváth, Judit , Investigators, KConFab, Investigators, HEBON, Izatt, Louise , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Johannsson, Oskar T., John, Esther M. , Kramer, Gero , Kroeldrup, Lone , Kruse, Torben A. , Lautrup, Charlotte Kvist , López‐Fernández, Adrià , Mai, Phuong L, Manoukian, Siranoush , Mátrai, Zoltán , Matricardi, Laura , Mebirouk, Noura, Meindl, Alfons , Montagna, Marco , Monteiro, Álvaro N.A. , Morrison, Patrick J. , Muranen, Taru , Nathanson, Katherine L. , Niederacher, Dieter , Oláh, Edith , Olopade, Olufunmilayo I. , Pedersen, Inge Søkilde , Peissel, Bernard , Peterlongo, Paolo , Petersen, Annabeth Høgh , Pinto, Pedro, Porteous, Mary, Pottinger, Caroline , Pujana, Miquel Angel, Ramser, Juliane, Rantala, Johanna, Rogers, Mark T., Rønlund, Karina, Abajo, A.M. SÁnchez De, Shah, Payal D. , Sharif, Saba , Side, Lucy, Stadler, Zsofia, Steele, Linda , Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Teulé, Àlex , Thull, Darcy L. , Trainer, Alison H., Tripathi, Vishakha , Valentini, Virginia , Viel, Alessandra , Walker, Lisa, Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Whaite, Anna , Offit, Kenneth, Thomassen, Mads , Schmutzler, Rita K., Simard, Jacques , Easton, Douglas F. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Pujana, Miguel Ángel , Dennis, Joe , Yang, Xin , Adlard, Julian , Agnarsson, Bjarni A , Andrulis, Irene L , Arason, Adalgeir , Arnold, Norbert , Auber, Bernd , Azzollini, Jacopo , Barkardottir, Rosa B , Barrowdale, Daniel , Benitez, Javier , Boonen, Susanne E , Bozsik, Aniko , Brennan, Paul , Brunet, Joan , Bucalo, Agostino , Caligo, Maria A , Campbell, Ian G , Cassingham, Hayley , Cini, Giulia , Claes, Kathleen B M , Coppa, Anna , Cortesi, Laura , Darder, Esther , de la Hoya, Miguel , de Putter, Robin , Del Valle, Jesús , Domchek, Susan M , Donaldson, Alan , Eason, Jacqueline , Engel, Christoph , Fostira, Florentia , Frone, Megan , Glendon, Gord , Godwin, Andrew K. , Greene, Mark H , Hahnen, Eric , Hanson, Helen , Izatt, Louise , Izquierdo, Angel , James, Paul , John, Esther M , Kroeldrup, Lone , Kruse, Torben A , Lazaro, Conxi , Lesueur, Fabienne , Matrai, Zoltan , Montagna, Marco , Monteiro, Alvaro N , Morrison, Patrick J , Muranen, Taru A , Nathanson, Katherine L , Neuhausen, Susan L. , Nevanlinna, H , Nguyen-Dumont, Tu , Niederacher, Dieter , Palli, Domenico , Parsons, Michael T , Perez-Segura, Pedro , Peterlongo, Paolo , Pinto, Pedro , Pottinger, Caroline , Radice, Paolo , Robson, Mark , Rump, Andreas , Sharif, Saba , Steele, Linda , Stoppa-Lyonnet, Dominique , Teixeira, Manuel R , Thull, Darcy L , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tommasi, Stefania , Toss, Angela , Tripathi, Vishakha , Valentini, Virginia , van Asperen, Christi J , Venturelli, Marta , Viel, Alessandra , Joseph, Vijai , Whaite, Anna , Simard, Jacques , Easton, Doug , Chenevix-Trench, Georgia , Ottini, Laura , Barnes, Daniel R , Leslie, Goska , Pujana, Miquel Angel , Eeles, Rosalind A , Evans, D Gareth , Matricardi, Laura , Olopade, Olufunmilayo I , Silvestri, Valentina , De Leeneer, Kim , Feliubadaló, Lidia , Hansen, Thomas van Overeem , Manoukian, Siranoush , Arnold, Norbert , Auber, Bernd , Balmañà, Judith , Barwell, Julian , Benı́tez, Javier , Bozsik, Anikó , Brady, Angela F., Buys, Saundra S. , Caligo, Maria A. , Campbell, Ian , Collaborators, GEMO Study, Collaborators, EMBRACE, Cook, Jackie A , Hoya, Miguel de la , Dı́ez, Orland , Domchek, Susan M. , Gallagher, David James , Hentschel, Julia , Investigators, KConFab, Investigators, HEBON, Izquierdo, Á. , Lázaro, Conxi , Lesueur, Fabienne , Mai, Phuong L, Maxwell, Kara N. , Meindl, Alfons , Nevanlinna, Heli , Nguyen‐Dumont, Tú , Palli, Domenico , Parsons, Michael T. , Radice, Paolo , Robson, Mark E. , Rump, Andreas , Singer, Christian F. , Stoppa‐Lyonnet, Dominique , Asperen, Christi J. van , Vijai, Joseph , Zanna, Ines , Couch, Fergus J. , Ottini, Laura
JNCI: Journal of the National Cancer Institute | July 26, 2021 | Volume: 114 | Issue: 1 | Pages: 109-122
AbstractBackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
Characterization of the Cancer Spectrum in Men With GermlineBRCA1andBRCA2Pathogenic Variants
Silvestri, Valentina , Group, and the CIMBA, Agnarsson, Bjarni A. , Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Barkardóttir, Rósa B. , Barroso, Alicia, Barrowdale, Daniel , Borg, Åke , Caldés, Trinidad , Claes, Kathleen , Cortesi, Laura , Ding, Yuan Chun , Easton, Douglas F. , Ejlertsen, Bent , Engel, Christoph , Evans, D. Gareth , Feliubadaló, Lídia , Géczi, Lajos , Glendon, Gord , Goldgar, David E. , Hahnen, Eric , Hogervorst, Frans B.L., Hulick, Peter J. , Izquierdo, Á. , James, Paul A. , Jensen, Uffe Birk , John, Esther M. , Konstantopoulou, Irene , Kurian, Allison W. , Kwong, Ava , Landucci, Elisabetta, Lesueur, Fabienne , Loud, Jennifer T. , Macháčková, Eva , Mai, Phuong L., Majidzadeh‐A, Keivan , Manoukian, Siranoush , Montagna, Marco , Nathanson, Katherine L. , Ngeow, Joanne , Ņikitina-Zaķe, Liene , Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I. , Osório, Ana , Park, Sue K. , Pedersen, Inge Søkilde , Petersen, Annabeth Høgh , Pinto, Pedro, Pujana, Miquel Angel, Rantala, Johanna, Rashid, Muhammad Usman , Rosenzweig, Barak , Rossing, Maria , Santamariña, Marta , Schmutzler, Rita K., Simard, Jacques , Solano, Ángela R. , Steele, Linda , Steinsnyder, Zoe , Tan, Yen Y. , Teixeira, Manuel R. , Teo, Soo‐Hwang , Terry, Mary Beth , Thomassen, Mads, Torres‐Esquius, Sara , Tung, Nadine, Vega, Ana , Viel, Alessandra , Vierstraete, Jeroen , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Wieme, Greet , Yoon, Sook‐Yee , McGuffog, Lesley, Hamann, Ute, Greene, Mark H. , Kirk, Judy A., Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Friedman, Eitan, Durocher, Francine , Pujana, Miguel Ángel , Hulick, Peter J , James, Paul , Lesueur, Fabienne , Pujana, Miquel Angel , Teixeira, Manuel R , Teo, Soo H , Vega, Ana , Weitzel, Jeffrey N , Claes, Kathleen B M , Evans, D Gareth , John, Esther M , Konstantopoulou, Irene , Olopade, Olufunmilayo I , Silvestri, Valentina , Wieme, Greet , Nathanson, Katherine L , Barrowdale, Daniel , Cortesi, Laura , Engel, Christoph , Izquierdo, Angel , Montagna, Marco , Pinto, Pedro , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Kurian, Allison W , Rashid, Muhammad U , Feliubadaló, Lidia , Santamariña, Marta , Ngeow, Joanne , Manoukian, Siranoush , Terry, Mary Beth , Kwong, Ava , Leslie, Goska , Barnes, Daniel R. , Group, and the CIMBA, Benı́tez, Javier , Bonanni, Bernardo , Borg, Åke , Buys, Saundra S. , Caligo, Maria A. , Capalbo, Carlo , Campbell, Ian , Chung, Wendy K. , Colonna, Sarah V. , Couch, Fergus J. , Hoya, Miguel de la , Dı́ez, Orland , Domchek, Susan M. , Foretová, Lenka , Fostira, Florentia , Gerdes, Anne‐Marie , Godwin, Andrew K. , Hopper, John L. , Isaacs, Claudine , Janavičius, Ramūnas , Vijai, Joseph , Mai, Phuong L., Moserle, Lidia , Mulligan, Anna Marie , Nevanlinna, Heli , Olah, Edith, Papi, Laura , Perez-Segura, Pedro , Porfirio, Berardino , Radice, Paolo , Senter, Leigha , Singer, Christian F. , Southey, Melissa C. , Stoppa‐Lyonnet, Dominique , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Zorn, Kristin K. , Parsons, Michael T. , Neuhausen, Susan L. , Rebbeck, Timothy R. , Tischkowitz, Marc D. , Friedman, Eitan, Ottini, Laura
JAMA Oncology | July 2, 2020 | Volume: 6 | Issue: 8 | Pages: 1218
Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness
Patel, Vivek , Busch, Evan L. , Cronin, Angel M., Leslie, Goska , McGuffog, Lesley, Adlard, Julian , Agata, Simona , Agnarsson, Bjarni A. , Ahmed, Munaza, Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Arason, Aðalgeir , Artioli, Grazia, Arver, Brita, Auber, Bernd , Azzollini, Jacopo , Barkardóttir, Rósa B. , Barroso, Alicia, Barrowdale, Daniel , Belotti, Muriel, Bertelsen, Birgitte , Blok, Marinus J. , Bodrogi, I., Bonadona, Valérie, Bondavalli, Davide , Boonen, Susanne E. , Borde, Julika , Borg, Åke , Bradbury, Angela R. , Brady, Angela, Brewer, Carole, Brunet, Joan , Buecher, Bruno , Caldés, Trinidad , Caliebe, Almuth , Calvello, Mariarosaria , Carrasco, Estela , Chan, Tsun Leung , Claes, Kathleen , Collaborators, GEMO Study, Collaborators, EMBRACE, Cortesi, Laura , Daly, Mary B., Damante, Giuseppe , Darder, Esther , Davidson, Rosemarie, Puppa, Lara Della , Ding, Yuan Chun , Ditsch, Nina , Donaldson, Alan, Dworniczak, Bernd , Easton, Douglas F. , Eccles, Diana M., Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , Engel, Christoph , Evans, D. Gareth , Faivre, Laurence, Faust, Ulrike , Feliubadaló, Lídia , Foretová, Lenka , Fountzilas, George , Frost, Debra, García‐Barberán, Vanesa , Gauthier‐Villars, Marion , Géczi, Lajos , Gehrig, Andrea, Gesta, Paul , Giannini, Giuseppe , Glendon, Gord , Goldgar, David E. , Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hamann, Ute, Hauke, Jan , Herold, Natalie, Hogervorst, Frans B.L., Honisch, Ellen, Hulick, Peter J. , Investigators, kConFab, Investigators, Hebon, Izatt, Louise , Jager, Agnes , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Jensen, Thomas D., Johannsson, Oskar T., John, Esther M. , Kang, Eunyoung , Kast, Karin, Kiiski, Johanna I. , Kim, Sung-Won, Ko, Kwang‐Pil , Konstantopoulou, Irene , Kramer, Gero , Krogh, Lotte, Kruse, Torben A., Kwong, Ava , Larsen, Mirjam, Lasset, Christine , Lautrup, Charlotte Kvist , Lee, Jihyoun , Lee, Jong Won, Lee, Min Hyuk , Lesueur, Fabienne , Liljegren, Annelie , Lindblom, Annika , Llovet, Patricia , López‐Fernández, Adrià , López‐Perolio, Irene, Lorca, Víctor , Loud, Jennifer T. , S.K., Edmond , Mai, Phuong L., Manoukian, Siranoush , Mari, Véronique , Martin, Lynn , Matricardi, Laura , Mebirouk, Noura, Medici, Veronica, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Miller, Clare , Gomes, D. Molina , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Navrátilová, Marie , Niederacher, Dieter , Nielsen, Finn C., Ņikitina-Zaķe, Liene , Offit, Kenneth, Oláh, Edith , Olopade, Olufunmilayo I. , Ong, Kai-Ren, Osório, Ana , Ott, Claus‐Eric , Park, Sue K. , Pedersen, Inge Søkilde , Peissel, Bernard , Peixoto, Ana , Peterlongo, Paolo , Petersen, Annabeth Høgh , Porteous, Mary, Pujana, Miguel Ángel , Ramser, Juliane, Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rizzolo, Piera , Rookus, Matti A. , Rossing, Caroline Maria, Ruddy, Kathryn J. , Santos, Catarina , Saule, Claire , Scarpitta, Rosa , Schmutzler, Rita K., Schuster, Hélène, Senter, Leigha , Seynaeve, Caroline, Shah, Payal D. , Silvestri, Valentina , Simard, Jacques , Skytte, Anne‐Bine , Snape, Katie , Solano, Ángela R. , Soucy, Penny, Sunde, Lone , Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Teo, Soo‐Hwang , Thomassen, Mads , Tibiletti, Maria Grazia , Toland, Amanda Ewart, Torres, Diana , Trainer, Alison H., Baan, Frederieke H. van der , Kolk, Lizet E. van der, Hest, Liselotte P. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Viel, Alessandra , Vierstraete, Jeroen , Villa, Roberta, Wachenfeldt, Anna von , Wagner, Philipp , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Wieme, Greet , Yadav, Siddhartha , Yoon, Sook‐Yee , Zanzottera, Cristina , Zorn, Kristin K. , D’Amico, Anthony V. , Freedman, Matthew L. , Pomerantz, Mark M., Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Ottini, Laura , Nielsen, Henriette Roed, Durocher, Francine , Eccles, Diana , Caputo, Sandrine M. , Faivre, Laurence , Leslie, Goska , Adlard, Julian , Arnold, Norbert , Auber, Bernd , Azzollini, Jacopo , Barnes, Daniel R , Brunet, Joan , Caligo, Maria A , Campbell, Ian G , Claes, Kathleen B M , Darder, Esther , Dennis, Joe , Dworniczak, Bernd , Eeles, Rosalind A , Ehrencrona, Hans , Ejlertsen, Bent , Evans, D Gareth , Garre, Pilar , Greene, Mark H , Hulick, Peter J , Jager, Agnes , James, Paul , John, Esther M , Joseph, Vijai , Kim, Sung-Won , Konstantopoulou, Irene , Lesueur, Fabienne , Matricardi, Laura , Gomes, Denise Molina , Nevanlinna, H , Olopade, Olufunmilayo I , Palli, Domenico , Park, Sue K , Parsons, Michael T , Peterlongo, Paolo , Petersen, Annabeth Høgh , Pujana, Miquel Angel , Ruddy, Kathryn J , Scarpitta, Rosa , Shah, Payal D , Silvestri, Valentina , Southey, Melissa C , Spurdle, Amanda B , Stoppa-Lyonnet, Dominique , Sunde, Lone , Teixeira, Manuel R , Teo, Soo H , Tommasi, Stefania , Toss, Angela , van der Luijt, Rob B , Vierstraete, Jeroen , Wieme, Greet , Yadav, Siddhartha , Antoniou, Antonis C , Eccles, Diana , Weitzel, Jeffrey N , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Boonen, Susanne E , Cortesi, Laura , Engel, Christoph , Hahnen, Eric , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Senter, Leigha , Faivre, Laurence , Rashid, Muhammad U , Calvello, Mariarosaria , Feliubadaló, Lidia , Hauke, Jan , Manoukian, Siranoush , Pomerantz, Mark M , Kwong, Ava , Lindblom, Annika , Friebel, Tara M. , Arnold, Norbert , Balmañà, Judith , Barnes, Daniel R. , Benı́tez, Javier , Bonadona, Valérie , Bonanni, Bernardo , Borg, Åke , Buys, Saundra S. , Cabezas-Camarero, Santiago , Caligo, Maria A. , Campbell, Ian , Carnevali, Ileana Wanda , Chu, Annie Tsz-Wai , Chung, Wendy K. , Cook, Jackie A , Couch, Fergus J. , Hoya, Miguel de la , Dı́ez, Orland , Domchek, Susan M. , Fostira, Florentia , Gerdes, Anne‐Marie , Godwin, Andrew K. , Herold, Natalie, Hopper, John L. , Jensen, Thomas Dyrso, Vijai, Joseph , Lasset, Christine , Lázaro, Conxi , Lemke, Johannes R. , Mai, Phuong L., Meindl, Alfons , Miller, Clare, Moserle, Lidia , Mulligan, Anna Marie , Nevanlinna, Heli , Palli, Domenico , Parsons, Michael T. , Perez-Segura, Pedro , Radice, Paolo , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Shin, Vivian Yvonne , Singer, Christian F. , Southey, Melissa C. , Spurdle, Amanda B. , Steele, Linda, Steinemann, Doris , Stoppa‐Lyonnet, Dominique , Stradella, Agostina , Tischkowitz, Marc D. , Tognazzo, Silvia , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Luijt, Rob B. van der , Yannoukakos, Drakoulis , Neuhausen, Susan L. , Rebbeck, Timothy R.
Cancer Research | November 13, 2019 | Volume: 80 | Issue: 3 | Pages: 624-638
Abstract Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3′ region of BRCA2 (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; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63–5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71–4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (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 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.
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification
Parsons, Michael T. , Tudini, Emma , Hahnen, Eric, Wappenschmidt, Barbara, Feliubadaló, Lídia , Aalfs, Cora M. , Agata, Simona, Aittomäki, Kristiina, Alducci, Elisa, Alonso‐Cerezo, María Concepción , Arnold, Norbert, Auber, Bernd , Austin, Rachel , Azzollini, Jacopo , Balmañà, Judith , Bartram, Claus R., Blümcke, Britta, Bonache, Sandra , Bonanni, Bernardo, Borg, Åke , Bortesi, Beatrice, Brunet, Joan , Bruzzone, Carla, Bucksch, Karolin , Cagnoli, Giulia , Caldés, Trinidad, Caliebe, Almuth , Calvello, Mariarosaria , Capone, Gabriele Lorenzo, Caputo, Sandrine M. , Carrasco, Estela , Caux‐Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia , Clarke, Edward , Cops, Elisa J., Cortesi, Laura , Couch, Fergus J., Darder, Esther , Debatin, Irmgard, Valle, Jesús Del , Delnatte, Capucine, Derive, Nicolas , Ditsch, Nina, Domchek, Susan M., Dutrannoy, Véronique, Eccles, Diana , Ehrencrona, Hans , Enders, Ute, Evans, D. Gareth , Farra, Chantal, Faust, Ulrike , Felbor, Ute , Feroce, Irène , Fine, Miriam, Galvão, Henrique C.R. , Gambino, Gaetana , Gehrig, Andrea, Gensini, Francesca , Germani, Aldo , Giesecke, J, Gómez, Carolina, Garcia, Encarna B., González, Sara , Grau, Èlia, Grill, Sabine , Groß, Eva, Guillaud‐Bataille, Marine , Gutiérrez‐Enríquez, Sara , Haaf, Thomas, Hackmann, Karl , Hansen, Thomas van Overeem , Harris, Marion, Hauke, Jan , Heinrich, T., Hellebrand, Heide, Herold, Karen, Honisch, Ellen, Horváth, Judit , Houdayer, Claude , Hübbel, Verena, Iglesias, Sílvia, Izquierdo, Á. , James, Paul A. , Janssen, Linda A.M., Jeschke, Udo, Kaulfuß, Silke , Keupp, Katharina, Kiechle, Marion , Kölbl, Alexandra C., Krieger, Sophie , Kruse, Torben A., Kvist, Anders , Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa , Lautrup, Charlotte Kvist , Ledig, Susanne, Leinert, Elena , Lim, Joanna , Loeffler, Markus, López‐Fernández, Adrià , Lucci‐Cordisco, Emanuela , Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica , Matricardi, Laura , Meindl, Alfons , Michelli, Rodrigo D., Moghadasi, Setareh , Moles‐Fernández, Alejandro , Montagna, Marco , Montalban, Gemma , Monteiro, Álvaro N.A. , Montes, Eva, Mori, Luigi , Müller, Clemens R., Mundhenke, Christoph , Naldi, Nadia, Nathanson, Katherine L. , Navarro, Matilde, Nichols, Cassandra , Niederacher, Dieter , Nielsen, Henriette Roed, Ong, Kai‐Ren , Pachter, Nicholas , Palmero, Edenir Inêz , Pedersen, Inge Søkilde , Peissel, Bernard , Pfeifer, Katharina, Pineda, Marta , Pohl‐Rescigno, Esther, Quante, Anne S. , Ramser, Juliane, Reis, Rui Manuel , Révillion, Françoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela , Rofes, Paula , Rump, Andreas , Salinas, Mónica, Abajo, A.M. SÁnchez De, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiß, Jochen, Solanes, Ares, Stiller, Mathias , Sullivan, Kelly J., Susman, Rachel , Sutter, Christian , Tavtigian, Sean V. , Teo, Soo‐Hwang , Thomassen, Mads, Tibiletti, Maria Grazia , Tognazzo, Silvia , Tornero, Eva , Törngren, Therese , Torres‐Esquius, Sara , Trainer, Alison, Tucker, Kathy , Asperen, Christi J. van, Mackelenbergh, Marion van , Varesco, Liliana, Vargas‐Parra, Gardenia , Varon, Raymonda, Vega, Ana , Velasco, Ángela, Vesper, Anne‐Sophie, Viel, Alessandra , Vreeswijk, Maaike P.G. , Wagner, Sebastian , Waha, Anke, Walker, Logan C., Walters, Rhiannon, Wang‐Gohrke, Shan , Weber, Bernhard , Weichert, Wilko , Wieland, Kerstin, Wöckel, Achim , Woodward, Emma R. , Zachariae, Silke , Zampiga, Valentina , Zeder-Göß, C, Investigators, KConFab, Lázaro, Conxi, Nicolo, Arcangela De , Radice, Paolo , Engel, Christoph , Schmutzler, Rita K., Goldgar, David E. , Manoukian, Siranoush , Gómez, E. , Houdayer, Claude , de la Hoya, Miguel , Diez, Orland , Eccles, Diana , Gutiérrez-Enríquez, Sara , Susman, Rachel , Tavtigian, Sean V , Toland, Amanda Ewart , Toss, Angela , Vega, Ana , Vreeswijk, Maaike P G , Woodward, Emma R , Radice, Paolo , Spurdle, Amanda B , James, Paul , Parsons, Michael T , Teo, Soo H , Monteiro, Alvaro N , Auber, Bernd , Azzollini, Jacopo , Brunet, Joan , Darder, Esther , Ehrencrona, Hans , Evans, D Gareth , Matricardi, Laura , Palmero, Edenir I , Nathanson, Katherine L , Pineda, Marta , Cini, Giulia , Cortesi, Laura , Del Valle, Jesús , Engel, Christoph , Izquierdo, Angel , Montagna, Marco , Rump, Andreas , Viel, Alessandra , Reis, Rui Manuel , Montalban, Gemma , Calvello, Mariarosaria , Feliubadaló, Lidia , Gómez-García, Encarna B , González, Sara , Hansen, Thomas van Overeem , Hauke, Jan , Zampiga, Valentina , De Nicolo, Arcangela , Manoukian, Siranoush , Li, Hongyan , Hahnen, Eric , Agata, Simona , Barbieri, Elena , Blanco, Ana , Bonanni, Bernardo , Bruzzone, Carla, Caligo, Maria A. , Carnevali, Ileana Wanda , Cavalli, Pietro , Concolino, Paola , Hoya, Miguel de la , Dean, Michael , Dı́ez, Orland , Farra, Chantal, Foulkes, William D. , Gerdes, Anne‐Marie , Gismondi, Viviana , Garcia, Encarna B., Guerrieri‐Gonzaga, Aliana , Guillaud-Bataille, Marine , Jeschke, Udo , Lewis, Alexandra L. , Loeffler, Markus, Meindl, Alfons , Moserle, Lidia , Navarro, Matilde, Nevanlinna, Heli , Papi, Laura , Perez-Segura, Pedro , Pohl‐Rescigno, Esther, Poplawski, Nicola Kazia , Porfirio, Berardino , Révillion, Françoise, Rhiem, Kerstin , Steinemann, Doris , Stoppa‐Lyonnet, Dominique , Sullivan, Kelly J., Teulé, Àlex , Tischkowitz, Marc D. , Asperen, Christi J. van , Varesco, Liliana , Velasco, Àngela , Weber, Bernhard H. F., Wiesmüller, Lisa , Witzel, Isabell , Investigators, kConFab, Lázaro, Conxi, Spurdle, Amanda B. , Balmaña, Judith , Austin, Rachel
Human Mutation | May 27, 2019 | Volume: 40 | Issue: 9 | Pages: 1557-1578
Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study
Qian, Frank , Wang, Shengfeng , McGuffog, Lesley, Barrowdale, Daniel , Oosterwijk, Jan C., Evans, D. Gareth , Engel, Christoph , Kast, Karin, Aalfs, Cora M. , Adank, Muriel A. , Agnarsson, Bjarni A. , Aittomäki, Kristiina, Alducci, Elisa, Andrulis, Irene L. , Ausems, Margreet G.E.M. , Azzollini, Jacopo , Barouk-Simonet, Emmanuelle, Belotti, Muriel, Benı́tez, Javier , Berger, Andreas, Borg, Åke , Bradbury, Angela R. , Brunet, Joan , Caldés, Trinidad , Caputo, Sandrine M. , Chiquette, Jocelyne , Collée, J. Margriet, Coupier, Isabelle, Daly, Mary B., Davidson, Rosemarie, Donaldson, Alan, Dorfling, Cecilia M., Eeles, Rosalind A. , Feliubadaló, Lídia , Foretová, Lenka , Fowler, Jeffrey M., Friedman, Eitan , Frost, Debra, Ganz, Patricia A. , García‐Barberán, Vanesa , Glendon, Gord , Gómez, E. , Hahnen, Eric , Hamann, Ute, Henderson, Alex, Hendricks, Carolyn B., Hulick, Peter J. , Imyanitov, Evgeny N., Izatt, Louise , Jakubowska, Anna , Kaczmarek, Katarzyna, Kang, Eunyoung , Kets, Carolien M., Kim, Sung-Won, Kwong, Ava , Laitman, Yael , Lasset, Christine, Lee, Min Hyuk , Lee, Jong Won, Lee, Jihyoun , Lester, Jenny, Lesueur, Fabienne , Loud, Jennifer T. , Mebirouk, Noura, Meijers‐Heijboer, Hanne , Meindl, Alfons , Montagna, Marco , Mooij, Thea M. , Mouret‐Fourme, Emmanuelle, Nathanson, Katherine L. , Niederacher, Dieter , Offit, Kenneth, Oláh, Edith , Ong, Kai-Ren, Ottini, Laura , Park, Sue K. , Peterlongo, Paolo , Pfeiler, Georg , Phelan, Catherine M., Poppe, Bruce , Pradhan, Nisha , Radice, Paolo , Ramus, Susan J. , Rantala, Johanna, Rodriguez, Gustavo C. , Schmutzler, Rita K., Selkirk, Christina G. , Shah, Payal D. , Simard, Jacques , Sutter, Christian , Tan, Yen Y. , Teixeira, R , Teo, Soo‐Hwang , Terry, Mary Beth , Thomassen, Mads , Toland, Amanda Ewart, Tucker, Kathy , Engelen, Klaartje van , Rensburg, Elizabeth J. van , Wang‐Gohrke, Shan , Wappenschmidt, Barbara , Weitzel, Jeffrey N. , Collaborators, GEMO Study, HEBON, EMBRACE, Greene, Mark H. , Rookus, Matti A. , Easton, Douglas F. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Goldgar, David E., Olopade, Olufunmilayo I. , Huo, Dezheng , Durocher, Francine , Teixeira, Manuel R. , Mitchell, Jonathan A. , Białkowska, Katarzyna , Hulick, Peter J , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Radice, Paolo , Weitzel, Jeffrey N , Azzollini, Jacopo , Brunet, Joan , Eeles, Rosalind A , Evans, D Gareth , Olopade, Olufunmilayo I , Jakubowska, Anna , Nathanson, Katherine L , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Ottini, Laura , Mitchell, Jonathan S. , Leslie, Goska , Chung, Wendy K. , Adlard, Julian , Arun, Banu , Barwell, Julian , Borg, Åke , Buys, Saundra S. , Caligo, Maria A. , Campbell, Ian , Claes, Kathleen , Couch, Fergus J. , Dı́ez, Orland , Domchek, Susan M. , Garber, Judy E. , Godwin, Andrew K. , Gronwald, Jacek , Hopper, John L. , Isaacs, Claudine , Izquierdo, Á. , Karlan, Beth Y. , Kim, Sung-Won , Lasset, Christine , Lubiński, Jan , Meindl, Alfons , Miller, Austin , Morrison, Patrick J. , Neuhausen, Susan L. , Nevanlinna, Heli , Nielsen, Finn Cilius , Nussbaum, Robert L. , Robson, Mark E. , Singer, Christian F. , Giles, Graham G , Stoppa‐Lyonnet, Dominique , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Yannoukakos, Drakoulis , Collaborators, GEMO Study, HEBON, EMBRACE, Rebbeck, Timothy R. , Feliubadaló, Lidia , Gómez-García, Encarna B , Terry, Mary Beth , Kwong, Ava
JNCI: Journal of the National Cancer Institute | July 3, 2018 | Volume: 111 | Issue: 4 | Pages: 350-364
Association of Type and Location ofBRCA1andBRCA2Mutations With Risk of Breast and Ovarian Cancer
Rebbeck, Timothy R., Sinilnikova, Olga M., Healey, Sue, McGuffog, Lesley, Mazoyer, Sylvie , Chenevix‐Trench, Georgia , Easton, Douglas F. , Antoniou, Antonis C. , Nathanson, Katherine L. , Laitman, Yael , Kushnir, Anya, Berger, Raanan , Zidan, Jamal, Friedman, Eitan , Ehrencrona, Hans , Stenmark‐Askmalm, Marie , Einbeigi, Zakaria , Loman, Niklas, Harbst, Katja , Rantala, Johanna, Melin, Beatrice , Olopade, Olufunmilayo I. , Seldon, Joyce, Ganz, Patricia A. , Chan, Salina, Odunsi, Kunle , Gayther, Simon A. , Lu, Karen H., Mitchell, Gillian, Walsh, Christine , Lester, Jenny, Ross, Eric A. , Daly, Mary B., Whittemore, Alice S. , John, Esther M. , Miron, Alexander, Terry, Mary Beth , Goldgar, David E., Tihomirova, Laima, Dorfling, Cecilia M., Rensburg, Elizabeth J. van , Ding, Yuan Chun , Ejlertsen, Bent , Gerdes, Anne‐Marie , Osório, Ana , Benı́tez, Javier , Godino, Javier, Tejada, María‐Isabel , Durán, M. , Weitzel, Jeffrey N. , Bobolis, Kristie, Sand, Sharon , Fontaine, Annette Campbell, Savarese, Antonella , Pasini, Barbara , Peissel, Bernard , Zaffaroni, Daniela , Vignolo-Lutati, Francesca, Scuvera, Giulietta, Giannini, Giuseppe , Bernard, Loris, Genuardi, Maurizio , Radice, Paolo , Dolcetti, Riccardo , Manoukian, Siranoush , Pensotti, Valeria , Yannoukakos, Drakoulis , Torres, Diana , Rashid, Muhammad Usman , Hamann, Ute, Peock, Susan, Frost, Debra, Platte, Radka, Evans, D. Gareth , Eeles, Rosalind A. , Davidson, Rosemarie, Eccles, Diana , Cole, Trevor, Brewer, Carole, Hodgson, Shirley, Walker, Lisa, Porteous, Mary, Kennedy, M. John, Izatt, Louise , Adlard, Julian , Donaldson, Alan, Ellis, Steve, Sharma, Priyanka , Schmutzler, Rita K., Wappenschmidt, Barbara , Becker, Alexandra, Rhiem, Kerstin, Hahnen, Eric , Engel, Christoph , Meindl, Alfons , Engert, Stefanie, Ditsch, Nina , Plendl, Hans Jörg, Mundhenke, Christoph , Niederacher, Dieter , Fleisch, Markus C. , Sutter, Christian , Bartram, Claus R., Dikow, Nicola , Wang‐Gohrke, Shan , Gadzicki, Dorothea, Kast, Karin, Varon-Mateeva, Raymonda, Gehrig, Andrea, Houdayer, Claude , Belotti, Muriel, Gauthier‐Villars, Marion , Boutry‐Kryza, Nadia, Lasset, Christine, Sobol, Hagay , Peyrat, Jean‐Philippe, Muller, Danièle, Fricker, Jean‐Pierre , Collonge‐Rame, Marie‐Agnès , Mortemousque, Isabelle, Noguès, Catherine , Rouleau, Étienne , Paepe, Anne De , Poppe, Bruce , Claes, Kathleen , Piedmonte, Marion, Rodriguez, Gustavo C. , Wakely, Katie, Boggess, John F., Blank, Stephanie V. , Basil, Jack, Phillips, Kelly‐Anne , Caldés, Trinidad , Hoya, Miguel de la , Romero, Atocha , Aittomäki, Kristiina, Hout, Annemarie H. van der, Hogervorst, Frans B.L., Verhoef, Senno, Collée, J. Margriet, Seynaeve, Caroline, Oosterwijk, Jan C., Gille, Johannes J. P., Gómez, E. , Kets, Carolien M., Ausems, Margreet G.E.M. , Aalfs, Cora M. , Devilee, Peter , Mensenkamp, Arjen R. , Kwong, Ava , Oláh, Edith , Papp, J., Dı́ez, Orland , Darder, Esther , Blanco, Ignacio , Salinas, Mónica, Jakubowska, Anna , Lubiński, Jan , Jaworska–Bieniek, Katarzyna, Durda, Katarzyna, Sukiennicki, Grzegorz, Huzarski, Tomasz , Byrski, Tomasz , Cybulski, Cezary, Tołoczko‐Grabarek, Aleksandra, Złowocka-Perłowska, Elżbieta , Menkiszak, Janusz , Arason, Aðalgeir , Barkardóttir, Rósa B. , Simard, Jacques , Laframboise, Rachel , Montagna, Marco , Alducci, Elisa, Peixoto, Ana , Teixeira, Manuel R. , Spurdle, Amanda B. , Lee, Min Hyuk , Park, Sue K. , Kim, Sung-Won, Friebel, Tara M. , Lindor, Noralane M. , Guidugli, Lucia, Foretová, Lenka , Vijai, Joseph , Offit, Kenneth, Robson, Mark E. , Rau‐Murthy, Rohini, Kauff, Noah D. , Fink-Retter, A., Singer, Christian F., Gschwantler‐Kaulich, Daphne , Pfeiler, Georg , Tea, Muy‐Kheng M., Berger, Andreas, Greene, Mark H. , Mai, Phuong L., Imyanitov, Evgeny N., Senter, Leigha , Bojesen, Anders , Pedersen, Inge Søkilde , Skytte, Anne‐Bine , Sunde, Lone , Thomassen, Mads , Moeller, Sanne Traasdahl, Kruse, Torben A., Jensen, Uffe Birk , Caligo, Maria A. , Aretini, Paolo , Teo, Soo‐Hwang , Selkirk, Christina G. , Hulick, Peter J. , Andrulis, Irene L. , Lu, Karen H. , Durocher, Francine , Thorne, Heather , Pankratz, Vernon S, Wang, Xianshu , Mitra, Nandita , Wan, Fei , Paluch–Shimon, Shani , Huo, Dezheng , Nussbaum, Robert L. , Domchek, Susan M. , Arun, Banu , Karlan, Beth Y. , Godwin, Andrew K. , Pathak, Harsh B. , Chung, Wendy K. , Buys, Saundra S. , Janavičius, Ramūnas , Tung, Nadine , Steele, Linda Roslyn , Neuhausen, Susan L. , Hansen, Thomas van Overeem , Cajal, Teresa Ramón y , Godino, Javier, Bonanni, Bernardo , Gismondi, Viviana , Fostira, Florentia , Garber, Judy E. , Cook, Jackie A , Morrison, Patrick J. , Kennedy, M. John, Ellis, Steve, Meindl, Alfons , Arnold, Norbert , Steinemann, Doris , Beer, Marit A. de , Weber, Bernhard H. F. , Stoppa‐Lyonnet, Dominique , Houdayer, Claude , Damiola, Francesca , Lasset, Christine , Isaacs, Claudine , Leeneer, Kim De , Azodi, Masoud , Nevanlinna, Heli , Gille, Johannes J. P., Wijnen, Juul , Lázaro, Conxi , Gronwald, Jacek , Agata, Simona , Couch, Fergus J. , Pankratz, V. Shane , Tischkowitz, Marc D. , Singer, Christian F. , Rappaport, Christine , Mai, Phuong L., Toland, Amanda Ewart , Caligo, Maria A , Hulick, Peter J , Spurdle, Amanda B , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Eccles, Diana , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Weitzel, Jeffrey N , Claes, Kathleen B M , Adlard, Julian , Darder, Esther , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , Joseph, Vijai , Olopade, Olufunmilayo I , Sunde, Lone , Menkiszak, Janusz , Jakubowska, Anna , Romero, Atocha , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Benitez, Javier , Engel, Christoph , Montagna, Marco , Robson, Mark , Simard, Jacques , Chenevix-Trench, Georgia , Huzarski, Tomasz , Senter, Leigha , Rashid, Muhammad U , Gómez-García, Encarna B , Pasini, Barbara , Yannoukakos, Drakoulis , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Sharma, Priyanka , Phillips, Kelly-Anne , Terry, Mary Beth , Kwong, Ava , Rhiem, Kerstin
JAMA | April 7, 2015 | Volume: 313 | Issue: 13 | Pages: 1347
Candidate Genetic Modifiers for Breast and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
Peterlongo, Paolo , Chang-Claude, Jenny, Moysich, Kirsten B., Schmutzler, Rita K., Simard, Jacques , Soucy, Penny, Eeles, Rosalind A. , Easton, Douglas F. , Hamann, Ute, Wilkening, Stefan, Chen, Bowang , Rookus, Matti A. , Schmidt, Marjanka K. , Baan, Frederieke H. van der , Spurdle, Amanda B. , Walker, Logan C. , Lose, Felicity , Maia, Ana-Teresa , Montagna, Marco , Matricardi, Laura , Lubiński, Jan , Jakubowska, Anna , Gómez, E. , Olopade, Olufunmilayo I., Nathanson, Katherine L. , Rebbeck, Timothy R., Arun, Banu K., Karlan, Beth Y., Oršulić, Sandra , Lester, Jenny, Chung, Wendy K., Miron, Alex, Southey, Melissa C. , Goldgar, David E., Janavičius, Ramūnas , Dorfling, Cecilia M., Rensburg, Elizabeth J. van , Ding, Yuan Chun , Neuhausen, Susan L., Hansen, Thomas van Overeem , Gerdes, Anne‐Marie , Ejlertsen, Bent , Jønson, Lars, Osório, Ana , Martínez-Bouzas, Cristina, Benı́tez, Javier , Conway, Edye E., Blazer, Kathleen R. , Weitzel, Jeffrey N. , Manoukian, Siranoush , Peissel, Bernard , Zaffaroni, Daniela , Scuvera, Giulietta, Barile, Monica, Ficarazzi, Filomena , Mariette, Frédérique, Fortuzzi, Stefano , Viel, Alessandra , Giannini, Giuseppe , Papi, Laura , Martayan, Aline , Tibiletti, Maria Grazia , Radice, Paolo , Vratimos, Athanassios, Fostira, Florentia, Donaldson, Alan, Brewer, Carole, Foo, Claire, Evans, D. Gareth , Frost, Debra, Eccles, Diana , Brady, Angela, Adlard, Julian , Walker, Lisa, Izatt, Louise , Side, Lucy E., Rogers, Mark T., Porteous, Mary, Morrison, Patrick J., Platte, Radka, Davidson, Rosemarie, Hodgson, Shirley V. , Ellis, Steve, Cole, Trevor, EMBRACE, on behalf of, Claes, Kathleen , Maerken, Tom Van, Meindl, Alfons , Gehrig, Andrea, Sutter, Christian , Engel, Christoph , Niederacher, Dieter , Plendl, Hansjoerg, Kast, Karin, Rhiem, Kerstin, Ditsch, Nina , Varon-Mateeva, Raymonda, Wappenschmidt, Barbara , Wang-Gohrke, Shan, Paillerets, Brigitte Bressac–de , Buecher, Bruno , Delnatte, Capucine, Houdayer, Claude , Coupier, Isabelle, Barjhoux, Laure, Venat‐Bouvet, Laurence , Boutry‐Kryza, Nadia, Sinilnikova, Olga M., Caron, Olivier , Mazoyer, Sylvie , Belotti, Muriel, Collaborators, on behalf of GEMO Study, Piedmonte, Marion, Friedländer, Michael , Rodriguez, Gustavo C., Copeland, Larry J. , Hoya, Miguel de la , Segura, Pedro Pérez, Nevanlinna, Heli , Aittomäki, Kristiina, Os, Theo A.M. van, Meijers-Heijboer, Hanne E.J., Hout, Annemarie H. van der, Hoogerbrugge, Nicoline, Ausems, Margreet G.E.M. , Doorn, Helena C. van , Collée, Margriet , HEBON, on behalf of, Oláh, Edith , Dı́ez, Orland , Blanco, Ignacio , Lázaro, Conxi , Brunet, Joan , Feliubadaló, Lídia , Cybulski, Cezary, Durda, Katarzyna, Jaworska–Bieniek, Katarzyna, Sukiennicki, Grzegorz, Arason, Aðalgeir , Chiquette, Jocelyne , Teixeira, Manuel R. , Olswold, Curtis, Lindor, Noralane M. , Offit, Kenneth, Corines, Marina, Jacobs, Lauren , Robson, Mark E. , Zhang, Liying , Vijai, Joseph , Berger, Andreas, Singer, Christian F., Rappaport, Christine , Kaulich, Daphne Geschwantler, Pfeiler, Georg , Tea, Muy-Kheng M., Phelan, Catherine M., Greene, Mark H. , Mai, Phuong L., Rennert, Gad , Mulligan, Anna Marie , Glendon, Gord , Tchatchou, Sandrine, Andrulis, Irene L., Bojesen, Anders , Pedersen, Inge Søkilde , Thomassen, Mads , Jensen, Uffe Birk , Laitman, Yael , Rantala, Johanna, Wachenfeldt, Anna von , Ehrencrona, Hans , Askmalm, Marie Stenmark, Borg, Åke , Kuchenbaecker, Karoline B., McGuffog, Lesley, Barrowdale, Daniel , Healey, Sue, Lee, Andrew , Chenevix‐Trench, Georgia , Investigators, on behalf of KConFab, Antoniou, Antonis C. , Friedman, Eitan , Durocher, Francine , Olopade, Olufunmilayo I. , Hoogerbrugge, Nicoline , Thorne, Heather , Stenmark‐Askmalm, Marie , Wang, Xianshu , Chang‐Claude, Jenny, Moysich, Kirsten B. , Rudolph, Anja , Nussbaum, Robert L. , Domchek, Susan M. , Arun, Banu , By, Karlan, Chung, Wendy K. , Buys, Saundra S. , Garber, Judy E. , Cook, Jackie A , Tischkowitz, Marc D. , Barwell, Julian , Kennedy, Michael John , Ellis, Steve, EMBRACE, on behalf of, Godwin, Andrew K. , Meindl, Alfons , Steinemann, Doris , Arnold, Norbert , Wang-Gohrke, Shan, Stoppa‐Lyonnet, Dominique , Damiola, Francesca , Golmard, Lisa , Pujol, Pascal , Collaborators, on behalf of GEMO Study, Meijers‐Heijboer, Hanne , Vreeswijk, Maaike P.G. , Hoogerbrugge, Nicoline, HEBON, on behalf of, Gronwald, Jacek , Couch, Fergus J. , Szabo, Csilla I. , Singer, Christian F , Mai, Phuong L., Toland, Amanda Ewart , Pharoah, Paul D.P. , Investigators, on behalf of KConFab, Nevanlinna, H , Peterlongo, Paolo , Rennert, Gad , Spurdle, Amanda B , Teixeira, Manuel R , van Rensburg, Elizabeth J , Eccles, Diana , Moysich, Kirsten , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Weitzel, Jeffrey N , Claes, Kathleen B M , Adlard, Julian , Brunet, Joan , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , Joseph, Vijai , Matricardi, Laura , Olopade, Olufunmilayo I , Southey, Melissa C , Jakubowska, Anna , Schmidt, Marjanka K , Nathanson, Katherine L , Friedlander, Michael , Arason, Adalgeir , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Lazaro, Conxi , Montagna, Marco , Robson, Mark , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Feliubadaló, Lidia , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Manoukian, Siranoush , Lubinski, Jan , Rhiem, Kerstin
Cancer Epidemiology, Biomarkers & Prevention | October 22, 2014 | Volume: 24 | Issue: 1 | Pages: 308-316
Abstract Background:BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies. Cancer Epidemiol Biomarkers Prev; 24(1); 308–16. ©2014 AACR.
Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2
Gaudet, Mia M. , Antoniou, Antonis C. , Ramus, Susan J. , Kuchenbaecker, Karoline , Soucy, Penny, Chen, Xiaoqing, Kirchhoff, Tomas , McGuffog, Lesley, Barrowdale, Daniel , Healey, Sue, Sinilnikova, Olga M., Andrulis, Irene L. , Özçelik, Hilmi, Mulligan, Anna Marie , Thomassen, Mads , Gerdes, Anne‐Marie , Jensen, Uffe Birk , Skytte, Anne‐Bine , Kruse, Torben A., Caligo, Maria A. , Wachenfeldt, Anna von , Barbany, Gisela , Loman, Niklas, Soller, Maria , Ehrencrona, Hans , Karlsson, Per , Nathanson, Katherine L. , Rebbeck, Timothy R., Jakubowska, Anna , Lubiński, Jan , Jaworska, Katarzyna, Durda, Katarzyna, Złowocka, Elżbieta, Huzarski, Tomasz , Byrski, Tomasz , Cybulski, Cezary, Górski, Bohdan , Osório, Ana , Durán, M. , Tejada, María‐Isabel , Hamann, Ute, Hogervorst, Frans B.L., Os, Theo A. van, Leeuwen, Flora E. van , Meijers‐Heijboer, Hanne , Blok, Marinus J. , Kets, Marleen, Hooning, Maartje J. , Oldenburg, Rogier A., Ausems, Margreet G.E.M. , Peock, Susan, Frost, Debra, Ellis, Steve D., Platte, Radka, Fineberg, Elena, Evans, D. Gareth , Jacobs, Chris , Eeles, Rosalind A. , Adlard, Julian , Davidson, Rosemarie, Eccles, Diana M., Cole, Trevor, Paterson, Joan, Brewer, Carole, Douglas, Fiona, Hodgson, Shirley V. , Walker, Lisa, Porteous, Mary, Kennedy, M. John, Side, Lucy, Bove, Betsy, Fassy-Colcombet, Marion, Castéra, Laurent , Cornelis, François, Mazoyer, Sylvie , Léoné, Mélanie, Boutry‐Kryza, Nadia, Paillerets, Brigitte Bressac–de , Coupier, Isabelle, Delnatte, Capucine, Akloul, Linda, Lynch, Henry T., Snyder, Carrie, Daly, Mary B., Terry, Mary Beth , John, Esther M. , Miron, Alexander, Southey, Melissa C. , Goldgar, David E., Singer, Christian F., Rappaport, Christine , Tea, Muy‐Kheng M., Fink-Retter, Anneliese, Hansen, Thomas van Overeem , Nielsen, Finn C., Arason, Aðalgeir , Vijai, Joseph , Shah, Sohela, Sarrel, Kara , Piedmonte, Marion, Phillips, Kelly, Basil, Jack, Rubinstein, Wendy S. , Boggess, John F., Wakeley, Katie, Montagna, Marco , Imyanitov, Evgeny N., Janavičius, Ramūnas , Lázaro, Conxi , Blanco, Ignacio , Feliubadaló, Lídia , Brunet, Joan , Gayther, Simon A. , Odunsi, Kunle , Walsh, Christine , Oláh, Edith , Teo, Soo‐Hwang , Ganz, Patricia A. , Beattie, Mary, Rensburg, Elizabeth J. van , Dorfling, Cecelia M., Dı́ez, Orland , Kwong, Ava , Schmutzler, Rita K., Wappenschmidt, Barbara, Engel, Christoph , Meindl, Alfons , Ditsch, Nina , Arnold, Norbert , Heidemann, Simone , Niederacher, Dieter , Preisler‐Adams, Sabine, Gadzicki, Dorothea, Varon-Mateeva, Raymonda, Deißler, Helmut , Gehrig, Andrea, Sutter, Christian , Kast, Karin, Fiebig, Britta, Heinritz, Wolfram, Caldes, Trinidad, Hoya, Miguel de la , Muranen, Taru , Nevanlinna, Heli , Spurdle, Amanda B. , Ding, Yuan Chun , Lindor, Noralane M. , Fredericksen, Zachary, Pankratz, V. Shane , Peterlongo, Paolo , Manoukian, Siranoush , Peissel, Bernard , Zaffaroni, Daniela , Barile, Monica, Bernard, Loris, Viel, Alessandra , Giannini, Giuseppe , Varesco, Liliana , Radice, Paolo , Greene, Mark H. , Mai, Phuong L., Easton, Douglas F., Chenevix‐Trench, Georgia , Offit, Kenneth, Simard, Jacques , Durocher, Francine , Eccles, Diana , Thorne, Heather , Phillips, Kelly‐Anne , Couch, Fergus J. , Beesley, Jonathan , Chen, Xiaoqing, Wang, Xianshu , Lee, Andrew , Domchek, Susan M. , Gronwald, Jacek , Benı́tez, Javier , Wijnen, Juul , Eccles, Diana M., Cook, Jackie A , Morrison, Patrick J. , Kennedy, M. John, Godwin, Andrew K. , Stoppa‐Lyonnet, Dominique , Caron, Olivier , Pujol, Pascal , Buys, Saundra S. , Chung, Wendy K. , Hopper, John L. , Singer, Christian F. , Robson, Mark E. , Phillips, Kelly, Toland, Amanda Ewart , Agata, Simona , Isaacs, Claudine , Pharoah, Paul D.P. , Karlan, Beth Y. , Meindl, Alfons , Varon-Mateeva, Raymonda, Caldes, Trinidad, Tischkowitz, Marc D. , Neuhausen, Susan L. , Mai, Phuong L., Nevanlinna, H , Caligo, Maria A , Peterlongo, Paolo , Ramus, Susan J , Spurdle, Amanda B , Teo, Soo H , van Rensburg, Elizabeth J , Eccles, Diana , de la Hoya, Miguel , Diez, Orland , Radice, Paolo , Adlard, Julian , Arnold, Norbert , Brunet, Joan , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , Joseph, Vijai , Southey, Melissa C , Jakubowska, Anna , Muranen, Taru A , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Engel, Christoph , Lazaro, Conxi , Montagna, Marco , Viel, Alessandra , Simard, Jacques , Chenevix-Trench, Georgia , Huzarski, Tomasz , Feliubadaló, Lidia , Hansen, Thomas van Overeem , Manoukian, Siranoush , Lubinski, Jan , Phillips, Kelly-Anne , Terry, Mary Beth , Kwong, Ava
Cancer Epidemiology, Biomarkers & Prevention | March 29, 2012 | Volume: 21 | Issue: 4 | Pages: 645-657
Abstract Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07–1.27; P = 7.42 × 10−4] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73–0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94–1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers. We also found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05–1.29; P = 3.8 × 10−4) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10–1.52; P = 1.8 × 10−3). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 21(4); 645–57. ©2012 AACR.