Citations 11
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.
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations
Friebel, Tara M. , Friedman, Eitan , Hamann, Ute, Huo, Dezheng , Kwong, Ava , Oláh, Edith , Olopade, Olufunmilayo I., Solano, Ángela R. , Teo, Soo‐Hwang , Thomassen, Mads , Weitzel, Jeffrey N. , Chan, TL, Couch, Fergus J., Goldgar, David E., Kruse, Torben A., Palmero, Edenir Inêz , Park, Sue K. , Torres, Diana , Rensburg, Elizabeth J. van , McGuffog, Lesley, Aalfs, Cora M. , Abugattas, Julio E. , Aittomäki, Kristiina, Andrews, Lesley , Andrulis, Irene L., Arason, Aðalgeir , Arun, Banu, Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo , Balmañà, Judith , Barile, Monica, Barkardóttir, Rósa B. , Barrowdale, Daniel , Benı́tez, Javier , Berger, Andreas, Berger, Raanan , Blanco, Amie , Blazer, Kathleen R. , Blok, Marinus J. , Bonadona, Valérie , Bradbury, Angela R. , Brewer, Carole, Buecher, Bruno , Caldés, Trinidad, Caliebe, Almuth , Caligo, Maria A. , Caputo, Sandrine M. , Chiquette, Jocelyne , Claes, Kathleen , Collée, J. Margriet, Davidson, Rosemarie, Hoya, Miguel de la , Leeneer, Kim De , Pauw, Antoine De , Delnatte, Capucine, Ding, Yuan Chun , Ditsch, Nina , Dorfling, Cecilia M., Dworniczak, Bernd , Eason, Jacqueline , Easton, Douglas F. , Eeles, Rosalind A. , Ehrencrona, Hans , Ejlertsen, Bent , EMBRACE, Engel, Christoph , Engert, Stefanie, Evans, D. Gareth , Faivre, Laurence, Feliubadaló, Lídia , Ferrer, Sandra Fert, Foretová, Lenka , Fowler, Jeffrey M., Frost, Debra, Galvão, Henrique C.R. , Ganz, Patricia A. , Gauthier‐Villars, Marion , Gehrig, Andrea, Collaborators, GEMO Study, Gerdes, Anne‐Marie , Gesta, Paul , Giannini, Giuseppe , Giraud, Sophie , Glendon, Gord , Godwin, Andrew K., Greene, Mark H. , Gutierrez‐Barrera, Angelica M. , Hahnen, Eric , Hauke, Jan , HEBON, Henderson, Alex, Hogervorst, Frans B. L., Honisch, Ellen, Imyanitov, Evgeny N., Izatt, Louise , Izquierdo, Á. , Jakubowska, Anna , James, Paul A. , Janavičius, Ramūnas , Jensen, Uffe Birk , Vijai, Joseph , Kaczmarek, Katarzyna, Karlan, Beth Y., Kast, Karin, Investigators, kConFab, Kim, Sung-Won, Konstantopoulou, Irene , Korach, Jacob, Laitman, Yael , Lasset, Christine, Lázaro, Conxi , Lee, Annette, Lee, Min Hyuk , Lester, Jenny, Lesueur, Fabienne , Liljegren, Annelie, Lindor, Noralane M. , Longy, Michel, Loud, Jennifer T. , Lu, Karen H. , Lubiński, Jan , Macháčková, Eva , Manoukian, Siranoush , Mari, Véronique , Martínez-Bouzas, Cristina, Mátrai, Zoltán , Mebirouk, Noura, Meijers‐Heijboer, Hanne , Meindl, Alfons , Mensenkamp, Arjen R. , Mickys, Ugnius, Montagna, Marco , Moysich, Kirsten B., Mulligan, Anna Marie , Musinsky, Jacob, Ngeow, Joanne , Niederacher, Dieter , Nielsen, Henriette Roed, Nielsen, Finn C., Offit, Kenneth, Öfverholm, Anna , Ong, Kai‐Ren , Osório, Ana , Papp, J., Pasini, Barbara , Pedersen, Inge Søkilde , Peixoto, Ana , Peruga, Nina, Peterlongo, Paolo , Pohl, Esther, Pradhan, Nisha , Prajzendanc, Karolina , Prieur, Fabienne, Radice, Paolo , Ramus, Susan J. , Rantala, Johanna, Rashid, Muhammad Usman , Rhiem, Kerstin, Rodriguez, Gustavo C. , Rogers, Mark T., Rudaitis, Vilius , Schmidt, Ane Yde , Schmutzler, Rita K., Senter, Leigha , Shah, Payal D. , Side, Lucy, Simard, Jacques , Skytte, Anne‐Bine , Slavin, Thomas P. , Snape, Katie , Sobol, Hagay, Southey, Melissa C. , Sukiennicki, Grzegorz, Sutter, Christian , Tan, Yen Y. , Teixeira, Manuel R. , Terry, Mary Beth , Teulé, Àlex , Thomas, Abigail, Thull, Darcy L. , Tognazzo, Silvia , Toland, Amanda Ewart, Topka, Sabine , Trainer, Alison H. , Hout, Annemieke H. van der, Kolk, Lizet E. van der, Luijt, Rob B. van der , Heetvelde, Mattias Van , Varesco, Liliana, Varon‐Mateeva, Raymonda, Vega, Ana , Villarreal‐Garza, Cynthia , Wachenfeldt, Anna von , Walker, Lisa, Wang‐Gohrke, Shan , Wappenschmidt, Barbara, Yoon, Sook-Yee, Zanzottera, Cristina, Zidan, Jamal, Zorn, Kristin K. , Selkirk, Christina G. , Hulick, Peter J. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Nathanson, Katherine L. , Durocher, Francine , Olopade, Olufunmilayo I. , Faivre, Laurence , Białkowska, Katarzyna , Caligo, Maria A , Hulick, Peter J , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , van Rensburg, Elizabeth J , Moysich, Kirsten , Vega, Ana , de la Hoya, Miguel , Radice, Paolo , Weitzel, Jeffrey N , Claes, Kathleen B M , Azzollini, Jacopo , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , Joseph, Vijai , Konstantopoulou, Irene , Olopade, Olufunmilayo I , Southey, Melissa C , van der Luijt, Rob B , Jakubowska, Anna , Palmero, Edenir I , Torres, Diana , Nathanson, Katherine L , Arason, Adalgeir , Barrowdale, Daniel , Benitez, Javier , Engel, Christoph , Izquierdo, Angel , Lazaro, Conxi , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Senter, Leigha , Topka, Sabine , Rebbeck, Timothy R. , Couch, Fergus J. , Parsons, Michael T. , Leslie, Goska , Adlard, Julian , Agata, Simona , Arnold, Norbert , Bonanni, Bernardo , Buys, Saundra S. , Campbell, Ian , Chung, Wendy K. , Cook, Jackie A , Dı́ez, Orland , Domchek, Susan M. , Velázquez, Carolina , EMBRACE, Garber, Judy E. , Collaborators, GEMO Study, Gronwald, Jacek , HEBON, Hentschel, Julia , Hogervorst, Frans B.L., Isaacs, Claudine , John, Esther M. , Karlan, Beth Y. , Lasa, Adriana , Lasset, Christine , Liljegren, Annelie , Meindl, Alfons , Miller, Austin , Moysich, Kirsten B. , Neuhausen, Susan L. , Nevanlinna, Heli , Nguyen, Huu Phuc , Nussbaum, Robert L. , Papi, Laura , Pujol, Pascal , Rhiem, Kerstin , Robson, Mark E. , Sharma, Priyanka , Singer, Christian F. , Sobol, Hagay , Steele, Linda Roslyn , Steinemann, Doris , Szabo, Csilla I. , Tischkowitz, Marc D. , Toland, Amanda Ewart , Tung, Nadine , Asperen, Christi J. van , Varesco, Liliana , Varon-Mateeva, Raymonda, Wappenschmidt, Barbara , Weber, Bernhard H. F. , Yannoukakos, Drakoulis , Spurdle, Amanda B. , Faivre, Laurence , Rashid, Muhammad U , De Leeneer, Kim , Feliubadaló, Lidia , Hauke, Jan , Pasini, Barbara , Ngeow, Joanne , Manoukian, Siranoush , Lubinski, Jan , Terry, Mary Beth , Villarreal-Garza, Cynthia , Balmaña, Judith , Kwong, Ava
Human Mutation | February 15, 2018 | Volume: 39 | Issue: 5 | Pages: 593-620
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.
Comparison of mRNA Splicing Assay Protocols across Multiple Laboratories: Recommendations for Best Practice in Standardized Clinical Testing
Whiley, Phillip J , Hoya, Miguel de la , Thomassen, Mads , Becker, Alexandra, Pedersen, Inge Søkilde , Montagna, Marco , Menéndez, Mireia , Quiles, Francisco, Gutiérrez‐Enríquez, Sara , Leeneer, Kim De , Tenés, Anna, Montalban, Gemma , Tserpelis, Demis, Yoshimatsu, Toshio F. , Tirapo, Carole, Raponi, Michela , Caldés, Trinidad , Blanco, Ana , Guidugli, Lucia, Garibay, Gorka Ruíz de , Wong, Ming, Tancredi, Mariella, Fachal, Laura , Ding, Yuan Chun , Kruse, Torben A., Lattimore, Vanessa , Kwong, Ava , Chan, Tsun Leung , Colombo, Mara , Vecchi, Giovanni De, Caligo, Maria A. , Baralle, Diana , Lázaro, Conxi , Radice, Paolo , Southey, Melissa C. , Houdayer, Claude , Fackenthal, Jim, Hansen, Thomas van Overeem , Vega, Ana , Dı́ez, Orland , Blok, Rien, Claes, Kathleen , Wappenschmidt, Barbara , Walker, Logan C. , Spurdle, Amanda B. , Brown, Melissa A. , Brandão, Rita D. , Santamariña, Marta , Couch, Fergus J. , Neuhausen, Susan L. , Caligo, Maria A , Spurdle, Amanda B , Vega, Ana , de la Hoya, Miguel , Diez, Orland , Gutiérrez-Enríquez, Sara , Radice, Paolo , Claes, Kathleen B M , Southey, Melissa C , Lazaro, Conxi , Montagna, Marco , Ruiz de Garibay, Gorka , Montalban, Gemma , De Leeneer, Kim , Hansen, Thomas van Overeem , Kwong, Ava , Fachal, Laura
Clinical Chemistry | November 8, 2013 | Volume: 60 | Issue: 2 | Pages: 341-352
Abstract BACKGROUND Accurate evaluation of unclassified sequence variants in cancer predisposition genes is essential for clinical management and depends on a multifactorial analysis of clinical, genetic, pathologic, and bioinformatic variables and assays of transcript length and abundance. The integrity of assay data in turn relies on appropriate assay design, interpretation, and reporting. METHODS We conducted a multicenter investigation to compare mRNA splicing assay protocols used by members of the ENIGMA (Evidence-Based Network for the Interpretation of Germline Mutant Alleles) consortium. We compared similarities and differences in results derived from analysis of a panel of breast cancer 1, early onset (BRCA1) and breast cancer 2, early onset (BRCA2) gene variants known to alter splicing (BRCA1: c.135-1G>T, c.591C>T, c.594-2A>C, c.671-2A>G, and c.5467+5G>C and BRCA2: c.426-12_8delGTTTT, c.7988A>T, c.8632+1G>A, and c.9501+3A>T). Differences in protocols were then assessed to determine which elements were critical in reliable assay design. RESULTS PCR primer design strategies, PCR conditions, and product detection methods, combined with a prior knowledge of expected alternative transcripts, were the key factors for accurate splicing assay results. For example, because of the position of primers and PCR extension times, several isoforms associated with BRCA1, c.594-2A>C and c.671-2A>G, were not detected by many sites. Variation was most evident for the detection of low-abundance transcripts (e.g., BRCA2 c.8632+1G>A Δ19,20 and BRCA1 c.135-1G>T Δ5q and Δ3). Detection of low-abundance transcripts was sometimes addressed by using more analytically sensitive detection methods (e.g., BRCA2 c.426-12_8delGTTTT ins18bp). CONCLUSIONS We provide recommendations for best practice and raise key issues to consider when designing mRNA assays for evaluation of unclassified sequence variants.
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.
Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in BRCA1 mutation carriers
Cox, David G. , Simard, Jacques , Sinnett, Daniel , Hamdi, Yosr , Soucy, Penny, Ouimet, Manon , Barjhoux, Laure, Verny-Pierre, Carole, McGuffog, Lesley , Healey, Sue, Greene, Mark H. , Mai, Phuong L., Andrulis, Irene L. , Network, Ontario Cancer Genetics, Thomassen, Mads , Gerdes, Anne‐Marie , Caligo, Maria A. , Friedman, Eitan , Laitman, Yael , Paluch, Shani Shimon, Borg, Åke , Karlsson, Per , Askmalm, Marie Stenmark, Bustinza, Gisela Barbany, Collaborators, SWE-BRCA, Nathanson, Katherine L. , Rebbeck, Timothy R., Hamann, Ute, Rookus, Matti A. , Ouweland, Ans M.W. van den, Ausems, Margreet G.E.M. , Aalfs, Cora M. , Gille, Hans J. J. P., HEBON, EMBRACE, Peock, Susan, Frost, Debra, Evans, D. Gareth , Eeles, Rosalind A. , Izatt, Louise , Adlard, Julian, Paterson, Joan, Eason, Jacqueline, Remon, Marie-Alice, Moncoutier, Virginie, Gauthier‐Villars, Marion , Lasset, Christine, Giraud, Sophie , Hardouin, Agnès, Berthet, Pascaline, Sobol, Hagay , Eisinger, François , Paillerets, Brigitte Bressac–de , Delnatte, Capucine, Collaborators, GEMO Study, Goldgar, David E., Miron, Alex, Özçelik, Hilmi, Southey, Melissa C. , Terry, Mary Beth , Registry, The Breast Cancer Family, Dressler, Anne-Catharina, Tea, Muy‐Kheng M., Hansen, Thomas van Overeem , Jóhannsson, Óskar Þór, Piedmonte, Marion, Rodriguez, Gustavo C. , Basil, Jack, Blank, Stephanie V. , Montagna, Marco , Blanco, Ignacio , Gayther, Simon A. , Moysich, Kirsten B., Schmutzler, Rita K., Wappenschmidt, Barbara , Engel, Christoph , Meindl, Alfons , Ditsch, Nina , Arnold, Norbert , Niederacher, Dieter , Sutter, Christian , Gadzicki, Dorothea, Fiebig, Britta, Caldes, Trinidad, Laframboise, Rachel , Nevanlinna, Heli , Chen, Xiaoqing, Spurdle, Amanda B. , Ding, Yuan Chun , Peterlongo, Paolo , Manoukian, Siranoush , Bernard, Loris, Radice, Paolo , Easton, Douglas F. , Chenevix‐Trench, Georgia , Antoniou, Antonis C. , Mazoyer, Sylvie, Sinilnikova, Olga M., Sinilnikova, Olga M., Dumont, Martine, Mai, Phuong , Greene, MH, Glendon, Gord, Selander, Teresa, Weerasooriya, Nayana , Karlsson, Per, Nordling, Margareta , Bergman, Annika, Einbeigi, Zakaria , Stenmark-Askmalm, Marie, Liedgren, S, Borg, Åke, Loman, Niklas, Olsson, Håkan , Kristoffersson, Ulf , Harbst, Katja , Henriksson, Karin, Lindblom, Annika , Arver, Brita, Wachenfeldt, Anna von , Liljegren, Annelie, Rantala, Johanna, Melin, Beatrice , Grönberg, Henrik , Stattin, Eva‐Lena , Emanuelsson, Monica, Ehrencrona, Hans , Seidel‐Renkert, Antje, Hogervorst, Frans B.L., Verhoef, S., Verheus, Martijn, Veer, Laura J. van’t , Leeuwen, Flora E. van , Rookus, M.A., Collée, Margriet , Ouweland, A.M.W. van den, Jager, Agnes , Hooning, Maartje J. , Tilanus‐Linthorst, Madeleine M.A., Seynaeve, Caroline, Asperen, C.J. van, Tollenaar, R.A., Devilee, P., Ligtenberg, M.J., Hoogerbrugge, Nicoline , Ausems, M.G., Aalfs, C.M., Os, T.A. van, Gille, J.J.P., Waisfisz, Quinten , Meijers‐Heijboer, Hanne , Gómez, E. , Roozendaal, Cees E. Van, Blok, Marinus J. , Caanen, BA, Oosterwijk, Jan C., Hout, Annemarie H. van der, Mourits, M J E , Vasen, Hans F. A. , Easton, Douglas F., Peock, Susan, Cook, Margaret, Frost, Debra, Platte, Radka, Miedzybrodzka, Zosia , Gregory, Helen , Jeffers, Lisa, Cole, T, Ong, Kai-Ren, Hoffman, Jonathan , Donaldson, Alan, James, Margaret, Paterson, Joan, Downing, Sarah, Murray, Alexandra, Rogers, Mark T., McCann, Emma, Kennedy, M. John, Barton, David , Porteous, Mary, Drummond, Sarah, Brewer, Carole, Kivuva, Emma , Searle, Anne, Goodman, Selina , Hill, Kathryn , Davidson, Rosemarie, Murday, Victoria, Bradshaw, Nicola, Snadden, Lesley, Longmuir, Mark, Watt, Catherine, Gibson, Sarah , Haque, Eshika, Tobias, Edward S. , Duncan, Alexis E. , Izatt, Louise, Jacobs, Chris , Langman, Caroline, Whaite, Anna , Barwell, Julian, Adlard, Julian, Chu, Carol , Miller, Julie, Ellis, Ian O. , Evans, D. Gareth, Lalloo, Fiona, Side, Lucy, Male, Alison , Berlin, Cheryl, Eason, Jacqueline , Collier, Rebecca, Douglas, Fiona, Claber, Oonagh, Jobson, Irene, Walker, Lisa, McLeod, Diane M., Halliday, Dorothy , Durell, Sarah, Stayner, Barbara, Eeles, Ros, Shanley, Susan, Rahman, Nazneen , Bancroft, Elizabeth, D'Mello, Lucia, Page, Elizabeth, Ardern‐Jones, Audrey, Castro, Elena , Robertson, Lisa , Bardsley, Cathryn, Hodgson, Shirley, Goff, Sheila, Brice, Glen , Winchester, Lizzie, Eddy, Charlotte, Tripathi, Vishakha , Attard, Virginia, Eccles, Diana , Lucassen, Anneke , Crawford, Gillian, McBride, Donna, Smalley, Sarah, Evans, D. Gareth, Lalloo, Fiona, Eeles, Ros, Bancroft, Elizabeth, D'Mello, Lucia, Sinilnikova, Olga, Sinilnikova, Olga, Giraud, Sophie, Léone, Mélanie, Mazoyer, Sylvie , Stoppa-Lyonnet, Dominique, Gauthier-Villars, Marion, Buecher, Bruno, Houdayer, Claude , Moncoutier, Virginie, Belotti, Muriel, Tirapo, Carole, Pauw, Antoine de, Bressac-de-Paillerets, Brigitte, Remenieras, Audrey, Byrde, Véronique, Lenoir, Gilbert, Bignon, Yves‐Jean , Uhrhammer, Nancy , Lasset, Christine, Bonadona, Valérie, Berthet, Pascaline, Bourdon, Violaine , Noguchi, Tetsuro, Eisinger, François, Coulet, Florence , Colas, Chrystelle , Soubrier, Florent , Coupier, Isabelle, Peyrat, Jean‐Philippe, Révillion, Françoise, Vennin, Philippe, Adenis, Claude, Rouleau, Étienne , Lidereau, Rosette, Demange, Liliane, Noguès, Catherine , Muller, Danièle, Fricker, Jean‐Pierre , Longy, Michel , Sevenet, Nicolas, Toulas, Christine , Guimbaud, Rosine, Gladieff, Laurence , Feillel, Viviane, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine , Coron, Fanny, Faivre, Laurence, Prieur, Fabienne, Lebrun, Marine, Ferrer, Sandra Fert, Frénay, Marc, Venat‐Bouvet, Laurence , Delnatte, Capucine, Mortemousque, Isabelle, Lynch, Henry T., Snyder, Carrie, Ejlertsen, Bent, Andersen, Mette Klarskov , Kjaergaard, Susanne, Sweet, Kevin , O’Connor, Michelle , Ramus, Susan, Pye, Carole, Wozniak, Eva , Varon-Mateeva, Raymonda, Kast, Karin, Preisler‐Adams, Sabine, Deißler, Helmut , Schönbuchner, Ines, Heinritz, Wolfram, Schäfer, Dieter, Aittomäki, Kristiina , Erkkilä, R.N. Irja, Thorne, Heather , Niedermayr, Eveline, Perez-Segura, Pedro, Durocher, Francine , John, Esther M. , Adlard, Julian , Stenmark‐Askmalm, Marie , Faivre, Laurence , Szabo, Csilla I. , Mai, Phuong L., Network, Ontario Cancer Genetics, Kaufman, Bella , Collaborators, SWE-BRCA, Domchek, Susan M. , Benı́tez, Javier , Asperen, Christi J. van , Devilee, Peter , HEBON, EMBRACE, Peock, Susan, Frost, Debra, Adlard, Julian, Paterson, Joan, Eason, Jacqueline, Godwin, Andrew K. , Lasset, Christine , Berthet, Pascaline, Caron, Olivier , Collaborators, GEMO Study, Buys, Saundra S. , Registry, The Breast Cancer Family, Singer, Christian F. , Dressler, Anne Catharina, Toland, Amanda Ewart , Isaacs, Claudine , Meindl, Alfons , Caldes, Trinidad, Chen, Xiaoqing, Beesley, Jonathan , Neuhausen, Susan L. , Couch, Fergus J. , Wang, Xianshu , Stoppa‐Lyonnet, Dominique , Mazoyer, Sylvie, Sinilnikova, Olga M., Dumont, Martine , Karlsson, Per, Borg, Åke, Soller, Maria , Jernström, Helena , Barbany, Gisela , Torres, Diana , Rashid, Muhammad Usman , Rookus, M.A., Asperen, C.J. van, Wijnen, Juul , Vreeswijk, Maaike P.G. , Devilee, P., Ligtenberg, M.J., Ausems, M.G., Luijt, Rob B. van der , Aalfs, C.M., Os, T.A. van, Gille, J.J.P., Easton, Douglas F., Cook, Margaret, Morrison, Patrick J. , Cole, Trevor, James, Margaret, Taylor, Amy , McCann, Emma, Kennedy, M. John, Snadden, Lesley, Izatt, Louise, Dorkins, Huw , Barwell, Julian, Adlard, Julian, Houghton, Catherine E. , Evans, D. Gareth, Lalloo, Fiona, Taylor, Jane Elizabeth , Berlin, Cheryl, Eeles, Ros, Houlston, Richard S. , Bancroft, Elizabeth, D'Mello, Lucia, Kohut, Kelly , Wiggins, Jennifer M. , Mitra, Anita , Cook, Jackie A , Quarrell, Oliver , Crawford, Gillian, Evans, D. Gareth, Lalloo, Fiona, Eeles, Ros, Bancroft, Elizabeth, D'Mello, Lucia, Sinilnikova, Olga, Sinilnikova, Olga, Giraud, Sophie, Stoppa-Lyonnet, Dominique, Moncoutier, Virginie, Pauw, Antoine de, Bressac-de-Paillerets, Brigitte, Remenieras, Audrey, Lasset, Christine, Bonadona, Valérie, Eisinger, François, Pujol, Pascal , Fournier, Joëlle , Vennin, Philippe, Delnatte, Capucine, Ejlertsen, Bent , Kjærgaard, Susanne, Senter, Leigha , Craven, Caroline M. , Pharoah, Paul D.P. , Harrington, Patricia , Blomqvist, Carl , Heikkinen, Tuomas , Hoya, Miguel de la , Nevanlinna, H , Caligo, Maria A , Peterlongo, Paolo , Spurdle, Amanda B , Eccles, Diana , Moysich, Kirsten , Radice, Paolo , Adlard, Julian , Arnold, Norbert , Eeles, Rosalind A , Ehrencrona, Hans , Evans, D Gareth , John, Esther M , Southey, Melissa C , Nathanson, Katherine L , Engel, Christoph , Montagna, Marco , Simard, Jacques , Chenevix-Trench, Georgia , Faivre, Laurence , Gómez-García, Encarna B , Hansen, Thomas van Overeem , Manoukian, Siranoush , Terry, Mary Beth , Lindblom, Annika , Ellis, Ian
Human Molecular Genetics | September 3, 2011 | Volume: 20 | Issue: 23 | Pages: 4732-4747
Genetic Variation in IGF2 and HTRA1 and Breast Cancer Risk among BRCA1 and BRCA2
Brummel, Sean S. , Ding, Yuan Chun , Steele, Linda, Nathanson, Katherine L. , Pfeiler, Georg , Lynch, Henry T., Weitzel, Jeffrey N. , Narod, Steven A. , Ganz, Patricia A. , Daly, Mary B., Olopade, Olufunmilayo I. , Rubinstein, Wendy S. , Blum, Joanne L. , Gillen, Daniel L. , Neuhausen, Susan L. , Domchek, Susan M. , Rebbeck, Timothy R. , Singer, Christian F. , Garber, Judy E. , Couch, Fergus J. , Godwin, Andrew K. , Isaacs, Claudine , Tomlinson, Gail Elizabeth , Tung, Nadine , Weitzel, Jeffrey N , Olopade, Olufunmilayo I , Nathanson, Katherine L
Cancer Epidemiology, Biomarkers & Prevention | August 8, 2011 | Volume: 20 | Issue: 8 | Pages: 1690-1702
Abstract Background: BRCA1 and BRCA2 mutation carriers have a lifetime breast cancer risk of 40% to 80%, suggesting the presence of risk modifiers. We previously identified significant associations in genetic variants in the insulin-like growth factor (IGF) signaling pathway. Here, we investigate additional IGF signaling genes as risk modifiers for breast cancer development in BRCA carriers. Methods: A cohort of 1,019 BRCA1 and 500 BRCA2 mutation carriers were genotyped for 99 single-nucleotide polymorphisms (SNP) in 13 genes. Proportional hazards regression was used to model time from birth to diagnosis of breast cancer for BRCA1 and BRCA2 carriers separately. For linkage disequilibrium (LD) blocks with multiple SNPs, an additive genetic model was used. For an SNP analysis, no additivity assumptions were made. Results: Significant associations were found between risk of breast cancer and LD blocks in IGF2 for BRCA1 and BRCA2 mutation carriers (global P values of 0.009 for BRCA1 and 0.007 for BRCA2), HTRA1 for BRCA1 carriers (global P value of 0.005), and MMP3 for BRCA2 carriers (global P = 0.0000007 for BRCA2). Conclusions: We identified significant associations of genetic variants involved in IGF signaling. With the known interaction of BRCA1 and IGF signaling and the loss of PTEN in a majority of BRCA1 tumors, this suggests that signaling through AKT may modify breast cancer risk in BRCA1 carriers. Impact: These results suggest potential avenues for future research targeting the IGF signaling pathway in modifying risk in BRCA1and BRCA2 mutation carriers. Cancer Epidemiol Biomarkers Prev; 20(8); 1690–702. ©2011 AACR.