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202. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Author

Barnes, Daniel R., primary, Rookus, Matti A., additional, McGuffog, Lesley, additional, Leslie, Goska, additional, Mooij, Thea M., additional, Dennis, Joe, additional, Mavaddat, Nasim, additional, Adlard, Julian, additional, Ahmed, Munaza, additional, Aittomäki, Kristiina, additional, Andrieu, Nadine, additional, Andrulis, Irene L., additional, Arnold, Norbert, additional, Arun, Banu K., additional, Azzollini, Jacopo, additional, Balmaña, Judith, additional, Barkardottir, Rosa B., additional, Barrowdale, Daniel, additional, Benitez, Javier, additional, Berthet, Pascaline, additional, Białkowska, Katarzyna, additional, Blanco, Amie M., additional, Blok, Marinus J., additional, Bonanni, Bernardo, additional, Boonen, Susanne E., additional, Borg, Åke, additional, Bozsik, Aniko, additional, Bradbury, Angela R., additional, Brennan, Paul, additional, Brewer, Carole, additional, Brunet, Joan, additional, Buys, Saundra S., additional, Caldés, Trinidad, additional, Caligo, Maria A., additional, Campbell, Ian, additional, Christensen, Lise Lotte, additional, Chung, Wendy K., additional, Claes, Kathleen B.M., additional, Colas, Chrystelle, additional, Collonge-Rame, Marie-Agnès, additional, Delnatte, Capucine, additional, Faivre, Laurence, additional, Giraud, Sophie, additional, Lasset, Christine, additional, Mari, Véronique, additional, Mebirouk, Noura, additional, Mouret-Fourme, Emmanuelle, additional, Schuster, Hélène, additional, Stoppa-Lyonnet, Dominique, additional, Antoniou, Antonis, additional, Cook, Jackie, additional, Davidson, Rosemarie, additional, Easton, Douglas, additional, Eeles, Ros, additional, Evans, D. Gareth, additional, Frost, Debra, additional, Hanson, Helen, additional, Izatt, Louise, additional, Ong, Kai-ren, additional, Side, Lucy, additional, O’Shaughnessy-Kirwan, Aoife, additional, Tischkowitz, Marc, additional, Walker, Lisa, additional, Daly, Mary B., additional, de la Hoya, Miguel, additional, de Putter, Robin, additional, Devilee, Peter, additional, Diez, Orland, additional, Ding, Yuan Chun, additional, Domchek, Susan M., additional, Dorfling, Cecilia M., additional, Dumont, Martine, additional, Ejlertsen, Bent, additional, Engel, Christoph, additional, Foretova, Lenka, additional, Fostira, Florentia, additional, Friedlander, Michael, additional, Friedman, Eitan, additional, Ganz, Patricia A., additional, Garber, Judy, additional, Gehrig, Andrea, additional, Gerdes, Anne-Marie, additional, Gesta, Paul, additional, Glendon, Gord, additional, Godwin, Andrew K., additional, Goldgar, David E., additional, González-Neira, Anna, additional, Greene, Mark H., additional, Gschwantler-Kaulich, Daphne, additional, Hahnen, Eric, additional, Hamann, Ute, additional, Hentschel, Julia, additional, Hogervorst, Frans B.L., additional, Hooning, Maartje J., additional, Horvath, Judit, additional, Hu, Chunling, additional, Hulick, Peter J., additional, Imyanitov, Evgeny N., additional, Chenevix-Trench, Georgia, additional, Phillips, Kelly-Anne, additional, Spurdle, Amanda, additional, Blok, Marinus, additional, Hogervorst, Frans, additional, Hooning, Maartje, additional, Koudijs, Marco, additional, Mensenkamp, Arjen, additional, Meijers-Heijboer, Hanne, additional, Rookus, Matti, additional, Engelen, Klaartje van, additional, Noguès, Catherine, additional, Isaacs, Claudine, additional, Izquierdo, Angel, additional, Jakubowska, Anna, additional, James, Paul A., additional, Janavicius, Ramunas, additional, John, Esther M., additional, Joseph, Vijai, additional, Karlan, Beth Y., additional, Kast, Karin, additional, Kruse, Torben A., additional, Kwong, Ava, additional, Laitman, Yael, additional, Lazaro, Conxi, additional, Lester, Jenny, additional, Lesueur, Fabienne, additional, Liljegren, Annelie, additional, Loud, Jennifer T., additional, Lubiński, Jan, additional, Mai, Phuong L., additional, Manoukian, Siranoush, additional, Meijers-Heijboer, Hanne E.J., additional, Meindl, Alfons, additional, Mensenkamp, Arjen R., additional, Miller, Austin, additional, Montagna, Marco, additional, Mukherjee, Semanti, additional, Mulligan, Anna Marie, additional, Nathanson, Katherine L., additional, Neuhausen, Susan L., additional, Nevanlinna, Heli, additional, Niederacher, Dieter, additional, Nielsen, Finn Cilius, additional, Nikitina-Zake, Liene, additional, Olah, Edith, additional, Olopade, Olufunmilayo I., additional, Osorio, Ana, additional, Ott, Claus-Eric, additional, Papi, Laura, additional, Park, Sue K., additional, Parsons, Michael T., additional, Pedersen, Inge Sokilde, additional, Peissel, Bernard, additional, Peixoto, Ana, additional, Peterlongo, Paolo, additional, Pfeiler, Georg, additional, Prajzendanc, Karolina, additional, Pujana, Miquel Angel, additional, Radice, Paolo, additional, Ramser, Juliane, additional, Ramus, Susan J., additional, Rantala, Johanna, additional, Rennert, Gad, additional, Risch, Harvey A., additional, Robson, Mark, additional, Rønlund, Karina, additional, Salani, Ritu, additional, Senter, Leigha, additional, Shah, Payal D., additional, Sharma, Priyanka, additional, Side, Lucy E., additional, Singer, Christian F., additional, Slavin, Thomas P., additional, Soucy, Penny, additional, Southey, Melissa C., additional, Spurdle, Amanda B., additional, Steinemann, Doris, additional, Steinsnyder, Zoe, additional, Sutter, Christian, additional, Tan, Yen Yen, additional, Teixeira, Manuel R., additional, Teo, Soo Hwang, additional, Thull, Darcy L., additional, Tognazzo, Silvia, additional, Toland, Amanda E., additional, Trainer, Alison H., additional, Tung, Nadine, additional, van Engelen, Klaartje, additional, van Rensburg, Elizabeth J., additional, Vega, Ana, additional, Vierstraete, Jeroen, additional, Wagner, Gabriel, additional, Wang-Gohrke, Shan, additional, Wappenschmidt, Barbara, additional, Weitzel, Jeffrey N., additional, Yadav, Siddhartha, additional, Yang, Xin, additional, Yannoukakos, Drakoulis, additional, Zimbalatti, Dario, additional, Offit, Kenneth, additional, Thomassen, Mads, additional, Couch, Fergus J., additional, Schmutzler, Rita K., additional, Simard, Jacques, additional, Easton, Douglas F., additional, and Antoniou, Antonis C., additional

Published
2020
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203. European polygenic risk score for prediction of breast cancer shows similar performance in Asian women

Author

Ho, Weang-Kee, primary, Tan, Min-Min, additional, Mavaddat, Nasim, additional, Tai, Mei-Chee, additional, Mariapun, Shivaani, additional, Li, Jingmei, additional, Ho, Peh-Joo, additional, Dennis, Joe, additional, Tyrer, Jonathan P., additional, Bolla, Manjeet K., additional, Michailidou, Kyriaki, additional, Wang, Qin, additional, Kang, Daehee, additional, Choi, Ji-Yeob, additional, Jamaris, Suniza, additional, Shu, Xiao-Ou, additional, Yoon, Sook-Yee, additional, Park, Sue K., additional, Kim, Sung-Won, additional, Shen, Chen-Yang, additional, Yu, Jyh-Cherng, additional, Tan, Ern Yu, additional, Chan, Patrick Mun Yew, additional, Muir, Kenneth, additional, Lophatananon, Artitaya, additional, Wu, Anna H., additional, Stram, Daniel O., additional, Matsuo, Keitaro, additional, Ito, Hidemi, additional, Chan, Ching Wan, additional, Ngeow, Joanne, additional, Yong, Wei Sean, additional, Lim, Swee Ho, additional, Lim, Geok Hoon, additional, Kwong, Ava, additional, Chan, Tsun L., additional, Tan, Su Ming, additional, Seah, Jaime, additional, John, Esther M., additional, Kurian, Allison W., additional, Koh, Woon-Puay, additional, Khor, Chiea Chuen, additional, Iwasaki, Motoki, additional, Yamaji, Taiki, additional, Tan, Kiak Mien Veronique, additional, Tan, Kiat Tee Benita, additional, Spinelli, John J., additional, Aronson, Kristan J., additional, Hasan, Siti Norhidayu, additional, Rahmat, Kartini, additional, Vijayananthan, Anushya, additional, Sim, Xueling, additional, Pharoah, Paul D. P., additional, Zheng, Wei, additional, Dunning, Alison M., additional, Simard, Jacques, additional, van Dam, Rob Martinus, additional, Yip, Cheng-Har, additional, Taib, Nur Aishah Mohd, additional, Hartman, Mikael, additional, Easton, Douglas F., additional, Teo, Soo-Hwang, additional, and Antoniou, Antonis C., additional

Published
2020
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204. GermlineAPOBEC3Bdeletion in Asian women increases somatic hypermutation in breast cancer that is associated with Her2 subtype,PIK3CAmutations, immune activation, and increased survival

Author

Pan, Jia-Wern, primary, Ahmad Zabidi, Muhammad Mamduh, additional, Chong, Boon-Keat, additional, Meng, Mei-Yee, additional, Ng, Pei-Sze, additional, Hasan, Siti Norhidayu, additional, Sandey, Bethan, additional, Bahnu, Saira, additional, Rajadurai, Pathmanathan, additional, Yip, Cheng-Har, additional, Rueda, Oscar M., additional, Caldas, Carlos, additional, Chin, Suet-Feung, additional, and Teo, Soo-Hwang, additional

Published
2020
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206. Health system strengthening: Integration of breast cancer care for improved outcomes

Author

Horton, Susan, primary, Camacho Rodriguez, Rolando, additional, Anderson, Benjamin O., additional, Aung, Soe, additional, Awuah, Baffour, additional, Delgado Pebé, Lucia, additional, Duggan, Catherine, additional, Dvaladze, Allison, additional, Kumar, Somesh, additional, Murillo, Raúl, additional, Mra, Rai, additional, Rositch, Anne F., additional, Songiso, Mutumba, additional, Sullivan, Richard, additional, Tsunoda, Audrey T., additional, Teo, Soo‐Hwang, additional, and Gelband, Hellen, additional

Published
2020
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207. The Molecular Landscape of Asian Breast Cancers Reveals Clinically Relevant Population-Specific Differences

Author

Pan, Jia-Wern, primary, Ahmad Zabidi, Muhammad Mamduh, additional, Ng, Pei-Sze, additional, Meng, Mei-Yee, additional, Hasan, Siti Norhidayu, additional, Sandey, Bethan, additional, Sammut, Stephen-John, additional, Yip, Cheng-Har, additional, Rajadurai, Pathmanathan, additional, Rueda, Oscar M., additional, Caldas, Carlos, additional, Chin, Suet-Feung, additional, and Teo, Soo-Hwang, additional

Published
2020
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208. Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants

Author

Shu, Xiang, primary, Long, Jirong, additional, Cai, Qiuyin, additional, Kweon, Sun-Seog, additional, Choi, Ji-Yeob, additional, Kubo, Michiaki, additional, Park, Sue K., additional, Bolla, Manjeet K., additional, Dennis, Joe, additional, Wang, Qin, additional, Yang, Yaohua, additional, Shi, Jiajun, additional, Guo, Xingyi, additional, Li, Bingshan, additional, Tao, Ran, additional, Aronson, Kristan J., additional, Chan, Kelvin Y. K., additional, Chan, Tsun L., additional, Gao, Yu-Tang, additional, Hartman, Mikael, additional, Kee Ho, Weang, additional, Ito, Hidemi, additional, Iwasaki, Motoki, additional, Iwata, Hiroji, additional, John, Esther M., additional, Kasuga, Yoshio, additional, Soon Khoo, Ui, additional, Kim, Mi-Kyung, additional, Kong, Sun-Young, additional, Kurian, Allison W., additional, Kwong, Ava, additional, Lee, Eun-Sook, additional, Li, Jingmei, additional, Lophatananon, Artitaya, additional, Low, Siew-Kee, additional, Mariapun, Shivaani, additional, Matsuda, Koichi, additional, Matsuo, Keitaro, additional, Muir, Kenneth, additional, Noh, Dong-Young, additional, Park, Boyoung, additional, Park, Min-Ho, additional, Shen, Chen-Yang, additional, Shin, Min-Ho, additional, Spinelli, John J., additional, Takahashi, Atsushi, additional, Tseng, Chiuchen, additional, Tsugane, Shoichiro, additional, Wu, Anna H., additional, Xiang, Yong-Bing, additional, Yamaji, Taiki, additional, Zheng, Ying, additional, Milne, Roger L., additional, Dunning, Alison M., additional, Pharoah, Paul D. P., additional, García-Closas, Montserrat, additional, Teo, Soo-Hwang, additional, Shu, Xiao-ou, additional, Kang, Daehee, additional, Easton, Douglas F., additional, Simard, Jacques, additional, and Zheng, Wei, additional

Published
2020
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209. Cancer Risks Associated With Germline PALB2 Pathogenic Variants: An International Study of 524 Families

Author

Yang, Xin, primary, Leslie, Goska, additional, Doroszuk, Alicja, additional, Schneider, Sandra, additional, Allen, Jamie, additional, Decker, Brennan, additional, Dunning, Alison M., additional, Redman, James, additional, Scarth, James, additional, Plaskocinska, Inga, additional, Luccarini, Craig, additional, Shah, Mitul, additional, Pooley, Karen, additional, Dorling, Leila, additional, Lee, Andrew, additional, Adank, Muriel A., additional, Adlard, Julian, additional, Aittomäki, Kristiina, additional, Andrulis, Irene L., additional, Ang, Peter, additional, Barwell, Julian, additional, Bernstein, Jonine L., additional, Bobolis, Kristie, additional, Borg, Åke, additional, Blomqvist, Carl, additional, Claes, Kathleen B.M., additional, Concannon, Patrick, additional, Cuggia, Adeline, additional, Culver, Julie O., additional, Damiola, Francesca, additional, de Pauw, Antoine, additional, Diez, Orland, additional, Dolinsky, Jill S., additional, Domchek, Susan M., additional, Engel, Christoph, additional, Evans, D. Gareth, additional, Fostira, Florentia, additional, Garber, Judy, additional, Golmard, Lisa, additional, Goode, Ellen L., additional, Gruber, Stephen B., additional, Hahnen, Eric, additional, Hake, Christopher, additional, Heikkinen, Tuomas, additional, Hurley, Judith E., additional, Janavicius, Ramunas, additional, Kleibl, Zdenek, additional, Kleiblova, Petra, additional, Konstantopoulou, Irene, additional, Kvist, Anders, additional, Laduca, Holly, additional, Lee, Ann S.G., additional, Lesueur, Fabienne, additional, Maher, Eamonn R., additional, Mannermaa, Arto, additional, Manoukian, Siranoush, additional, McFarland, Rachel, additional, McKinnon, Wendy, additional, Meindl, Alfons, additional, Metcalfe, Kelly, additional, Mohd Taib, Nur Aishah, additional, Moilanen, Jukka, additional, Nathanson, Katherine L., additional, Neuhausen, Susan, additional, Ng, Pei Sze, additional, Nguyen-Dumont, Tu, additional, Nielsen, Sarah M., additional, Obermair, Florian, additional, Offit, Kenneth, additional, Olopade, Olufunmilayo I., additional, Ottini, Laura, additional, Penkert, Judith, additional, Pylkäs, Katri, additional, Radice, Paolo, additional, Ramus, Susan J., additional, Rudaitis, Vilius, additional, Side, Lucy, additional, Silva-Smith, Rachel, additional, Silvestri, Valentina, additional, Skytte, Anne-Bine, additional, Slavin, Thomas, additional, Soukupova, Jana, additional, Tondini, Carlo, additional, Trainer, Alison H., additional, Unzeitig, Gary, additional, Usha, Lydia, additional, van Overeem Hansen, Thomas, additional, Whitworth, James, additional, Wood, Marie, additional, Yip, Cheng Har, additional, Yoon, Sook-Yee, additional, Yussuf, Amal, additional, Zogopoulos, George, additional, Goldgar, David, additional, Hopper, John L., additional, Chenevix-Trench, Georgia, additional, Pharoah, Paul, additional, George, Sophia H.L., additional, Balmaña, Judith, additional, Houdayer, Claude, additional, James, Paul, additional, El-Haffaf, Zaki, additional, Ehrencrona, Hans, additional, Janatova, Marketa, additional, Peterlongo, Paolo, additional, Nevanlinna, Heli, additional, Schmutzler, Rita, additional, Teo, Soo-Hwang, additional, Robson, Mark, additional, Pal, Tuya, additional, Couch, Fergus, additional, Weitzel, Jeffrey N., additional, Elliott, Aaron, additional, Southey, Melissa, additional, Winqvist, Robert, additional, Easton, Douglas F., additional, Foulkes, William D., additional, Antoniou, Antonis C., additional, and Tischkowitz, Marc, additional

Published
2020
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210. Association of Genomic Domains in BRCA1 and BRCA2 with Prostate Cancer Risk and Aggressiveness

Author

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

Published
2020
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211. Measurement challenge: protocol for international case–control comparison of mammographic measures that predict breast cancer risk

Author

Dench, Evenda, primary, Bond-Smith, Daniela, additional, Darcey, Ellie, additional, Lee, Grant, additional, Aung, Ye K, additional, Chan, Ariane, additional, Cuzick, Jack, additional, Ding, Ze Y, additional, Evans, Chris F, additional, Harvey, Jennifer, additional, Highnam, Ralph, additional, Hsieh, Meng-Kang, additional, Kontos, Despina, additional, Li, Shuai, additional, Mariapun, Shivaani, additional, Nickson, Carolyn, additional, Nguyen, Tuong L, additional, Pertuz, Said, additional, Procopio, Pietro, additional, Rajaram, Nadia, additional, Repich, Kathy, additional, Tan, Maxine, additional, Teo, Soo-Hwang, additional, Trinh, Nhut Ho, additional, Ursin, Giske, additional, Wang, Chao, additional, dos-Santos-Silva, Isabel, additional, McCormack, Valerie, additional, Nielsen, Mads, additional, Shepherd, John, additional, Hopper, John L, additional, and Stone, Jennifer, additional

Published
2019
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212. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers

Author

Page, Elizabeth C., primary, Bancroft, Elizabeth K., additional, Brook, Mark N., additional, Assel, Melissa, additional, Hassan Al Battat, Mona, additional, Thomas, Sarah, additional, Taylor, Natalie, additional, Chamberlain, Anthony, additional, Pope, Jennifer, additional, Raghallaigh, Holly Ni, additional, Evans, D. Gareth, additional, Rothwell, Jeanette, additional, Maehle, Lovise, additional, Grindedal, Eli Marie, additional, James, Paul, additional, Mascarenhas, Lyon, additional, McKinley, Joanne, additional, Side, Lucy, additional, Thomas, Tessy, additional, van Asperen, Christi, additional, Vasen, Hans, additional, Kiemeney, Lambertus A., additional, Ringelberg, Janneke, additional, Jensen, Thomas Dyrsø, additional, Osther, Palle J.S., additional, Helfand, Brian T., additional, Genova, Elena, additional, Oldenburg, Rogier A., additional, Cybulski, Cezary, additional, Wokolorczyk, Dominika, additional, Ong, Kai-Ren, additional, Huber, Camilla, additional, Lam, Jimmy, additional, Taylor, Louise, additional, Salinas, Monica, additional, Feliubadaló, Lidia, additional, Oosterwijk, Jan C., additional, van Zelst-Stams, Wendy, additional, Cook, Jackie, additional, Rosario, Derek J., additional, Domchek, Susan, additional, Powers, Jacquelyn, additional, Buys, Saundra, additional, O'Toole, Karen, additional, Ausems, Margreet G.E.M., additional, Schmutzler, Rita K., additional, Rhiem, Kerstin, additional, Izatt, Louise, additional, Tripathi, Vishakha, additional, Teixeira, Manuel R., additional, Cardoso, Marta, additional, Foulkes, William D., additional, Aprikian, Armen, additional, van Randeraad, Heleen, additional, Davidson, Rosemarie, additional, Longmuir, Mark, additional, Ruijs, Mariëlle W.G., additional, Helderman van den Enden, Apollonia T.J.M., additional, Adank, Muriel, additional, Williams, Rachel, additional, Andrews, Lesley, additional, Murphy, Declan G., additional, Halliday, Dorothy, additional, Walker, Lisa, additional, Liljegren, Annelie, additional, Carlsson, Stefan, additional, Azzabi, Ashraf, additional, Jobson, Irene, additional, Morton, Catherine, additional, Shackleton, Kylie, additional, Snape, Katie, additional, Hanson, Helen, additional, Harris, Marion, additional, Tischkowitz, Marc, additional, Taylor, Amy, additional, Kirk, Judy, additional, Susman, Rachel, additional, Chen-Shtoyerman, Rakefet, additional, Spigelman, Allan, additional, Pachter, Nicholas, additional, Ahmed, Munaza, additional, Ramon y Cajal, Teresa, additional, Zgajnar, Janez, additional, Brewer, Carole, additional, Gadea, Neus, additional, Brady, Angela F., additional, van Os, Theo, additional, Gallagher, David, additional, Johannsson, Oskar, additional, Donaldson, Alan, additional, Barwell, Julian, additional, Nicolai, Nicola, additional, Friedman, Eitan, additional, Obeid, Elias, additional, Greenhalgh, Lynn, additional, Murthy, Vedang, additional, Copakova, Lucia, additional, Saya, Sibel, additional, McGrath, John, additional, Cooke, Peter, additional, Rønlund, Karina, additional, Richardson, Kate, additional, Henderson, Alex, additional, Teo, Soo H., additional, Arun, Banu, additional, Kast, Karin, additional, Dias, Alexander, additional, Aaronson, Neil K., additional, Ardern-Jones, Audrey, additional, Bangma, Chris H., additional, Castro, Elena, additional, Dearnaley, David, additional, Eccles, Diana M., additional, Tricker, Karen, additional, Eyfjord, Jorunn, additional, Falconer, Alison, additional, Foster, Christopher, additional, Gronberg, Henrik, additional, Hamdy, Freddie C., additional, Stefansdottir, Vigdis, additional, Khoo, Vincent, additional, Lindeman, Geoffrey J., additional, Lubinski, Jan, additional, Axcrona, Karol, additional, Mikropoulos, Christos, additional, Mitra, Anita, additional, Moynihan, Clare, additional, Rennert, Gadi, additional, Suri, Mohnish, additional, Wilson, Penny, additional, Dudderidge, Tim, additional, Offman, Judith, additional, Kote-Jarai, Zsofia, additional, Vickers, Andrew, additional, Lilja, Hans, additional, and Eeles, Rosalind A., additional

Published
2019
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216. Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women

Author

Lawrenson, Kate, Song, Fengju, Hazelett, Dennis J, Kar, Siddhartha P, Tyrer, Jonathan, Phelan, Catherine M, Corona, Rosario I, Rodríguez-Malavé, Norma I, Seo, Ji-Hei, Adler, Emily, Coetzee, Simon G, Segato, Felipe, Fonseca, Marcos AS, Amos, Christopher I, Carney, Michael E, Chenevix-Trench, Georgia, Choi, Jiyeob, Doherty, Jennifer A, Jia, Weihua, Jin, Gang J, Kim, Byoung-Gie, Le, Nhu D, Lee, Juyeon, Li, Lian, Lim, Boon K, Adenan, Noor A, Mizuno, Mika, Park, Boyoung, Pearce, Celeste L, Shan, Kang, Shi, Yongyong, Shu, Xiao-Ou, Sieh, Weiva, Australian Ovarian Cancer Study Group, Thompson, Pamela J, Wilkens, Lynne R, Wei, Qingyi, Woo, Yin L, Yan, Li, Karlan, Beth Y, Freedman, Matthew L, Noushmehr, Houtan, Goode, Ellen L, Berchuck, Andrew, Sellers, Thomas A, Teo, Soo-Hwang, Zheng, Wei, Matsuo, Keitaro, Park, Sue, Chen, Kexin, Pharoah, Paul DP, Gayther, Simon A, Goodman, Marc T, Tyrer, Jonathan [0000-0003-3724-4757], Pharoah, Paul [0000-0001-8494-732X], and Apollo - University of Cambridge Repository

Subjects
Australian Ovarian Cancer Study Group, Genome-wide association study, Quantitative Trait Loci, Oncology and Carcinogenesis, Carcinoma, Ovarian Epithelial, eQTL, Polymorphism, Single Nucleotide, Asian ancestry, Paediatrics and Reproductive Medicine, Rare Diseases, Asian People, Clinical Research, Ovarian Epithelial, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Polymorphism, Aetiology, Cancer, Base Sequence, Prevention, Carcinoma, Human Genome, Single Nucleotide, Epithelial ovarian cancer, Gene regulation, Ovarian Cancer, Case-Control Studies, Female, Enhancer, Biotechnology
Abstract

OBJECTIVE: Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women. METHODS: Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations. RESULTS: At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10-9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10-9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP

Published
2019

217. Evaluation of Cancer-Based Criteria for Use in Mainstream BRCA1 and BRCA2 Genetic Testing in Patients With Breast Cancer

Author

Kemp, Zoe, Turnbull, Alice, Yost, Shawn, Seal, Sheila, Mahamdallie, Shazia, Poyastro-Pearson, Emma, Warren-Perry, Margaret, Eccleston, Anthony, Tan, Min-Min, Teo, Soo Hwang, Turner, Nicholas, Strydom, Ann, George, Angela, and Rahman, Nazneen

Subjects
Adult, Aged, 80 and over, BRCA2 Protein, BRCA1 Protein, Research, Cost-Benefit Analysis, Breast Neoplasms, Middle Aged, State Medicine, United Kingdom, Online Only, Oncology, Practice Guidelines as Topic, Humans, Female, Genetic Predisposition to Disease, Genetic Testing, Prospective Studies, Early Detection of Cancer, Original Investigation, Aged, Retrospective Studies
Abstract

Key Points Question How can BRCA1 and BRCA2 gene testing in patients with cancer be increased? Findings In this quality improvement study of 1184 individuals, 5 cancer-based criteria with a 10% mutation detection rate were used by the cancer team to approve genetic testing for patients with cancer. Meaning Mainstreaming genetic testing using simple, cancer-based criteria may provide an efficient way to implement consistent, transparent, equitable, cost-effective, patient-centered genetic testing., Importance Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers. Objective To evaluate mainstream genetic testing using cancer-based criteria in patients with cancer. Design, Setting, and Participants A quality improvement study and cost-effectiveness analysis of different BRCA testing selection criteria and access procedures to evaluate feasibility, acceptability, and mutation detection performance was conducted at the Royal Marsden National Health Service Foundation Trust as part of the Mainstreaming Cancer Genetics (MCG) Programme. Participants included 1184 patients with cancer who were undergoing genetic testing between September 1, 2013, and February 28, 2017. Main Outcomes and Measures Mutation rates, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios were the primary outcomes. Results Of the 1184 patients (1158 women [97.8%]) meeting simple cancer-based criteria, 117 had a BRCA mutation (9.9%). The mutation rate was similar in retrospective United Kingdom (10.2% [235 of 2294]) and prospective Malaysian (9.7% [103 of 1061]) breast cancer studies. If traditional family history criteria had been used, more than 50% of the mutation-positive individuals would have been missed. Of the 117 mutation-positive individuals, 115 people (98.3%) attended their genetics appointment and cascade to relatives is underway in all appropriate families (85 of 85). Combining with the equivalent ovarian cancer study provides 5 simple cancer-based criteria for BRCA testing with a 10% mutation rate: (1) ovarian cancer; (2) breast cancer diagnosed when patients are 45 years or younger; (3) 2 primary breast cancers, both diagnosed when patients are 60 years or younger; (4) triple-negative breast cancer; and (5) male breast cancer. A sixth criterion—breast cancer plus a parent, sibling, or child with any of the other criteria—can be added to address family history. Criteria 1 through 5 are considered the MCG criteria, and criteria 1 through 6 are considered the MCGplus criteria. Testing using MCG or MCGplus criteria is cost-effective with cost-effectiveness ratios of $1330 per discounted QALYs and $1225 per discounted QALYs, respectively, and appears to lead to cancer and mortality reductions (MCG: 804 cancers, 161 deaths; MCGplus: 1020 cancers, 204 deaths per year over 50 years). Use of MCG or MCGplus criteria might allow detection of all BRCA mutations in patients with breast cancer in the United Kingdom through testing one-third of patients. Feedback questionnaires from 259 patients and 23 cancer team members (12 oncologists, 8 surgeons, and 3 nurse specialists) showed acceptability of the process with 100% of patients pleased they had genetic testing and 100% of cancer team members confident to approve patients for genetic testing. Use of MCGplus criteria also appeared to be time and resource efficient, requiring 95% fewer genetic consultations than the traditional process. Conclusions and Relevance This study suggests that mainstream testing using simple, cancer-based criteria might be able to efficiently deliver consistent, cost-effective, patient-centered BRCA testing., This quality improvement study and cost-effectiveness analysis evaluates mainstream genetic testing using cancer-based criteria to determine eligibility for BRCA1 and BRCA2 testing in patients with breast cancer.

Published
2019

218. Fine-mapping of 150 breast cancer risk regions identifies 178 high confidence target genes

Author

Fachal, Laura, Aschard, Hugues, Beesley, Jonathan, Barnes, Daniel, Allen, Jamie, Kar, Siddhartha, Pooley, Karen, Dennis, Joe, Michailidou, Kyriaki, Turman, Constance, Soucy, Penny, Lemacon, Audrey, Lush, Michael, Tyrer, Jonathan, Ghoussaini, Maya, Moradi Marjaneh, Mahdi, Jiang, Xia, Agata, Simona, Aittomaki, Kristiina, Alonso, M. Rosario, Andrulis, Irene, Anton-Culver, Hoda, Antonenkova, Natalia, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan, Arun, Banu, Auber, Bernd, Auer, Paul, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa, Barrowdale, Daniel, Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bialkowska, Katarzyna, Blanco, Amie, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Stig, Bolla, Manjeet, Bonanni, Bernardo, Borg, Ake, Bosse, Kristin, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Brock, Ian, Brooks-Wilson, Angela, Bruning, Thomas, Burwinkel, Barbara, Buys, Saundra, Cai, Qiuyin, Caldes, Trinidad, Caligo, Maria, Camp, Nicola, Campbell, Ian, Canzian, Federico, Carroll, Jason, Carter, Brian, Castelao, Jose, Chiquette, Jocelyne, Christiansen, Hans, Chung, Wendy, Claes, Kathleen, Clarke, Christine, Collee, J. Margriet, Cornelissen, Sten, Couch, Fergus, Cox, Angela, Cross, Simon, Cybulski, Cezary, Czene, Kamila, Daly, Mary, de la Hoya, Miguel, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Dite, Gillian, Domchek, Susan, Dork, Thilo, dos-Santos-Silva, Isabel, Droit, Arnaud, Dubois, Stephane, Dumont, Martine, Duran, Mercedes, Durcan, Lorraine, Dwek, Miriam, Eccles, Diana, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter, Fletcher, Olivia, Floris, Giuseppe, Flyger, Henrik, Foretova, Lenka, Foulkes, William, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gabrielson, Marike, Gago-Dominguez, Manuela, Gambino, Gaetana, Ganz, Patricia, Gapstur, Susan, Garber, Judy, Garcia-Saenz, Jose, Gaudet, Mia, Georgoulias, Vassilios, Giles, Graham, Glendon, Gord, Godwin, Andrew, Goldberg, Mark, Goldgar, David, Gonzalez-Neira, Anna, Greene, Mark, Grip, Mervi, Gronwald, Jacek, Grundy, Anne, Guenel, Pascal, Hahnen, Eric, Haiman, Christopher, Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia, Hartikainen, Jaana, Hartman, Mikael, He, Wei, Healey, Catherine, Heemskerk-Gerritsen, Bernadette, Heyworth, Jane, Hillemanns, Peter, Hogervorst, Frans, Hollestelle, Antoinette, Hooning, Maartje, Hopper, John, Howell, Anthony, Huang, Guanmengqian, Hulick, Peter, Imyanitov, Evgeny, Isaacs, Claudine, Iwasaki, Motoki, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jankowitz, Rachel, John, Esther, Johnson, Nichola, Jones, Michael, Jukkola-Vuorinen, Arja, Jung, Audrey, Kaaks, Rudolf, Kang, Daehee, Karlan, Beth, Keeman, Renske, Kerin, Michael, Khusnutdinova, Elza, Kiiski, Johanna, Kirk, Judy, Kitahara, Cari, Ko, Yon-Dschun, Konstantopoulou, Irene, Kosma, Veli-Matti, Koutros, Stella, Kubelka-Sabit, Katerina, Kwong, Ava, Kyriacou, Kyriacos, Laitman, Yael, Lambrechts, Diether, Lee, Eunjung, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Lindblom, Annika, Lo, Wing-Yee, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer, Lubinski, Jan, MacInnis, Robert, Maishman, Tom, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Matsuo, Keitaro, Maurer, Tabea, Mavroudis, Dimitrios, Mayes, Rebecca, McGuffog, Lesley, McLean, Catriona, Mebirouk, Noura, Meindl, Alfons, Middha, Pooja, Miller, Nicola, Miller, Austin, Montagna, Marco, Moreno, Fernando, Mulligan, Anna Marie, Munoz-Garzon, Victor, Muranen, Taru, Narod, Steven, Nassir, Rami, Nathanson, Katherine, Neuhausen, Susan, Nevanlinna, Heli, Neven, Patrick, Nielsen, Finn, Nikitina-Zake, Liene, Norman, Aaron, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo, Olsson, Hakan, Orr, Nick, Osorio, Ana, Pankratz, V. Shane, Papp, Janos, Park, Sue, Park-Simon, Tjoung-Won, Parsons, Michael, Paul, James, Pedersen, Inge Sokilde, Peissel, Bernard, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Prajzendanz, Karolina, Prentice, Ross, Presneau, Nadege, Prokofyeva, Darya, Pujana, Miquel Angel, Pylkas, Katri, Radice, Paolo, Ramus, Susan, Rantala, Johanna, Rau-Murthy, Rohini, Rennert, Gad, Risch, Harvey, Robson, Mark, Romero, Atocha, Rossing, Caroline Maria, Saloustros, Emmanouil, Sanchez-Herrero, Estela, Sandler, Dale, Santamarina, Marta, Saunders, Christobel, Sawyer, Elinor, Scheuner, Maren, Schmidt, Daniel, Schmutzler, Rita, Schneeweiss, Andreas, Schoemaker, Minouk, Schottker, Ben, Schurmann, Peter, Scott, Christopher, Scott, Rodney, Senter, Leigha, Seynaeve, Caroline, Shah, Mitul, Sharma, Priyanka, Shen, Chen-Yang, Shu, Xiao-Ou, Singer, Christian, Slavin, Thomas, Smichkoska, Snezhana, Southey, Melissa, Spinelli, John, Spurdle, Amanda, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tamimi, Rulla, Tan, Yen Yen, Tapper, William, Taylor, Jack, Teixeira, Manuel, Tengstrom, Maria, Teo, Soo, Terry, Mary Beth, Teule, Alex, Thomassen, Mads, Thull, Darcy, Tibiletti, Maria Grazia, Tischkowitz, Marc, Toland, Amanda, Tollenaar, Rob, Tomlinson, Ian, Torres, Diana, Torres-Mejia, Gabriela, Troester, Melissa, Tung, Nadine, Tzardi, Maria, Ulmer, Hans-Ulrich, Vachon, Celine, van Asperen, Christi, van der Kolk, Lizet, van Rensburg, Elizabeth, Vega, Ana, Viel, Alessandra, Vijai, Joseph, Vogel, Maatje, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice, Weitzel, Jeffrey, Wendt, Camilla, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Wu, Anna, Yannoukakos, Drakoulis, Zhang, Yan, Zheng, Wei, Pharoah, Paul, Chang-Claude, Jenny, Garcia-Closas, Montserrat, Schmidt, Marjanka, Milne, Roger, Kristensen, Vessela, French, Juliet, Edwards, Stacey, Antoniou, Antonis, Chenevix-Trench, Georgia, Simard, Jacques, Easton, Douglas, Kraft, Peter, and Dunning, Alison

Subjects
0303 health sciences, Linkage disequilibrium, In silico, Computational biology, Biology, 3. Good health, Chromatin, DNA binding site, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Expression quantitative trait loci, Transcription factor, Gene, 030304 developmental biology, Genetic association
Abstract

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants (CCVs) in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium, and enriched genomic features to determine variants with high posterior probabilities (HPPs) of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of potentially causal variants, using gene expression (eQTL), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways, were over-represented among the 178 highest confidence target genes.

Published
2019
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219. Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations

Author

Bancroft, Elizabeth K, Saya, Sibel, Page, Elizabeth C, Myhill, Kathryn, Thomas, Sarah, Pope, Jennifer, Chamberlain, Anthony, Hart, Rachel, Glover, Wayne, Cook, Jackie, Rosario, Derek J, Helfand, Brian T, Selkirk, Christina Hutten, Davidson, Rosemarie, Longmuir, Mark, Eccles, Diana M, Gadea, Neus, Brewer, Carole, Barwell, Julian, Salinas, Monica, Greenhalgh, Lynn, Tischkowitz, Marc, Henderson, Alex, Evans, David Gareth, Buys, Saundra S, Eeles, Rosalind A, Aaronson, Neil K, Eeles, Rosalind, Bancroft, Elizabeth, Page, Elizabeth, Kote-Jarai, Zsofia, Ardern-Jones, Audrey, Bangma, Chris, Castro, Elena, Dearnaley, David, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C, Johannsson, Oskar Thor, Khoo, Vincent, Eccles, Diana, Lilja, Hans, Evans, Gareth, Eyfjord, Jorunn, Lubinski, Jan, Maehle, Lovise, Mikropoulos, Christos, Millner, Alan, Mitra, Anita, Offman, Judith, Moynihan, Clare, Rennert, Gad, Suri, Mohnish, Dias, Alex, Taylor, Natalie, D'Mello, Lucia, Pope, Jenny, James, Paul, Mitchell, Gillian, Shanley, Sue, Richardson, Kate, McKinley, Joanne, Petelin, Lara, Murphy, Morgan, Mascarenhas, Lyon, Murphy, Declan, Lam, Jimmy, Taylor, Louise, Miller, Cathy, Stapleton, Alan, Chong, Michael, Suthers, Graeme, Poplawski, Nicola, Tucker, Katherine, Andrews, Lesley, Duffy, Jessica, Millard, Richard, Ward, Robyn, Williams, Rachel, Stricker, Phillip, Kirk, Judy, Bowman, Michelle, Patel, Manish, Harris, Marion, O'Connell, Shona, Hunt, Clare, Smyth, Courtney, Frydenberg, Mark, Lindeman, Geoffrey, Shackleton, Kylie, Morton, Catherine, Susman, Rachel, McGaughran, Julie, Boon, Melanie, Pachter, Nicholas, Townshend, Sharron, Schofield, Lyn, Nicholls, Cassandra, Spigelman, Allan, Gleeson, Margaret, Amor, David, Burke, Jo, Patterson, Briony, Swindle, Peter, Scott, Rodney, Foulkes, William, Boshari, Talia, Aprikian, Armen, Jensen, Thomas, Bojeson, Anders, Osther, Palle, Skytte, Anne-Bine, Cruger, Dorthe, Tondering, Majbritt Kure, Gerdes, Anne-Marie, Schmutzler, Rita, Rhiem, Kerstin, Wihler, Petra, Kast, K, Griebsch, C, Johannsson, Oskar, Stefansdottir, Vigdis, Murthy, Vedang, Sarin, Rajiv, Awatagiri, Kasturi, Ghonge, Sujata, Kowtal, Pradnya, Mulgund, Gouri, Gallagher, David, Bambury, Richard, Farrell, Michael, Gallagher, Fergal, Kiernan, Ingrid, Friedman, Eitan, Chen-Shtoyerman, Rakefet, Basevitch, Alon, Leibovici, Dan, Melzer, Ehud, Ben-Yehoshua, Sagi Josefsberg, Nicolai, Nicola, Radice, Paolo, Valdagni, Riccardo, Magnani, Tiziana, Gay, Simona, Teo, Soo Hwang, Tan, Hui Meng, Yoon, Sook-Yee, Thong, Meow Keong, Vasen, Hans, Ringleberg, Janneke, van Asperen, Christi, Kiemeney, Bart, van Zelst-Stams, Wendy, Ausems, Margreet GEM, van der Luijt, Rob B, van Os, Theo, Ruijs, Marielle WG, Adank, Muriel A, Oldenburg, Rogier A, Helderman-van den Enden, A Paula TJM, Caanen, BAH, Oosterwijk, Jan C, Moller, Pal, Brennhovd, Bjorn, Medvik, Heidi, Hanslien, Eldbjorg, Grindedal, Eli Marie, Cybulski, Cezary, Wokolorczyk, Dominika, Teixeira, Manuel, Maia, Sofia, Peixoto, Ana, Henrique, Rui, Oliveira, Jorge, Goncalves, Nuno, Araujo, Luis, Seixas, Manuela, Souto, Joao Paulo, Nogueira, Pedro, Copakova, Lucia, Zgajnar, Janez, Krajc, Mateja, Vrecar, Alenka, Capella, Gabriel, Ramon y Cajal, Teresa, Fisas, David, Mora, Josefina, Esquena, Salvador, Balmana, Judith, Morote, Juan, Liljegren, Annelie, Hjalm-Eriksson, Marie, Ekdahl, Karl-Johan, Carlsson, Stefan, George, Angela, Kemp, Zoe, Wiggins, Jennifer, Moss, Cathryn, Van As, Nicholas, Thompson, Alan, Ogden, Chris, Woodhouse, Christopher, Kumar, Pardeep, Evans, D Gareth, Bulman, Barbara, Rothwell, Jeanette, Tricker, Karen, Wise, Gillian, Mercer, Catherine, McBride, Donna, Costello, Philandra, Pearce, Allison, Torokwa, Audrey, Paterson, Joan, Clowes, Virginia, Taylor, Amy, Newcombe, Barbara, Walker, Lisa, Halliday, Dorothy, Stayner, Barbara, Fleming-Brown, D, Snape, Katie, Hanson, Helen, Hodgson, Shirley, Brice, Glen, Homfray, Tessa, Hammond, Carrie, Kohut, Kelly, Anjum, Uruj, Dearing, Audrey, Mencias, Mark, Potter, Alison, Renton, Caroline, Searle, Anne, Hill, Kathryn, Goodman, Selina, Garcia, Lynda, Devlin, Gemma, Everest, Sarah, Nadolski, Maria, Douglas, Fiona, Jobson, Irene, Paez, Edgar, Donaldson, Alan, Tomkins, Sue, Langman, Caroline, Jacobs, Chris, Pichert, Gabriella, Shaw, Adam, Kulkarni, Anju, Tripathi, Vishakha, Rose, Sarah, Compton, Cecilia, Watson, Michelle, Reinholtz, Cherylin, Brady, Angela, Dorkins, Huw, Melville, Athalie, Kosicka-Slawinska, Monika, Cummings, Carole, Kiesel, Vicki, Bartlett, Marion, Randhawa, Kashmir, Ellery, Natalie, Side, Lucy, Male, Alison, Simon, Kate, Rees, Katie, Tidey, Lizzie, Gurasashvili, Jana, Nevitt, Louise, Ingram, Stuart, Howell, Alice, Rosario, Derek, Catto, James, Howson, Joanne, Ong, Kai-Ren, Chapman, Cyril, Cole, Trevor, Heaton, Tricia, Hoffman, Jonathan, Burgess, Lucy, Huber, Camilla, Islam, Farah, Watt, Cathy, Duncan, Alexis, Kockelbergh, Roger, Mzazi, Shumikazi, Dineen, Amy, Sattar, Ayisha, Kaemba, Beckie, Sidat, Zahirah, Patel, Nafisa, Siguake, Kas, Birt, Angela, Poultney, Una, Umez-Eronini, Nkem, Mom, Jaswant, Sutton, Vivienne, Cornford, Philip, Bermingham, Nicola, Yesildag, Pembe, Treherne, Katy, Griffiths, Julie, Cogley, Lyn, Gott, Hannah, Rubinstein, Wendy S, Hulick, Peter, McGuire, Michael, Shevrin, Daniel, Kaul, Karen, Weissman, Scott, Newlin, Anna, Vogel, Kristen, Weiss, Shelly, Hook, Nicole, Buys, Saundra, Goldgar, David, Conner, Tom, Venne, Vickie, Stephenson, Robert, Dechet, Christopher, Domchek, Susan, Powers, Jacquelyn, Rustgi, Neil, Strom, Sara, Arun, Banu, Davis, John W, Yamamura, Yuko, Obeid, Elias, Giri, Veda, Gross, Laura, Bealin, Lisa, Cooney, Kathy, Stoffel, Elena, Okoth, Linda, Comm, IMPACT Study Steering, Collaborators, IMPACT, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), General Practice, Urology, and Clinical Genetics

Subjects
psychosocial, Male, Health Knowledge, Attitudes, Practice, Urological Oncology, Genes, BRCA2, Genes, BRCA1, #pcsm, RISK PERCEPTION, Anxiety, Hospital Anxiety and Depression Scale, FAMILY-HISTORY, PSA, 0302 clinical medicine, Quality of life, QUALITY-OF-LIFE, Risk Factors, Surveys and Questionnaires, Medicine, 030212 general & internal medicine, Longitudinal Studies, Depressió psíquica, Early Detection of Cancer, POPULATION, Prostatic Neoplasms/diagnosis, education.field_of_study, Prostate cancer, Depression, Anxiety/etiology, Urology & Nephrology, Middle Aged, Distress, Prostate cancer screening, Mental depression, #ProstateCancer, Estudi de casos, 030220 oncology & carcinogenesis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort, HEALTH, medicine.symptom, Psychosocial, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, Urology, Depression/etiology, Population, HOSPITAL ANXIETY, Early Detection of Cancer/psychology, OVARIAN-CANCER, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, BRCA1/2, Internal medicine, Humans, education, Psychiatric Status Rating Scales, Càncer de pròstata, business.industry, Prostatic Neoplasms, BRCA1, BRCA2, quality of life, Case-Control Studies, Mutation, Perception, Case studies, business, PSYCHOLOGICAL IMPACT
Abstract

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICIPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS:A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening.

Published
2019

220. Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk

Author

Yang, Yaohua, Wu, Lang, Shu, Xiang, Lu, Yingchang, Shu, Xiao-Ou, Cai, Qiuyin, Beeghly-Fadiel, Alicia, Li, Bingshan, Ye, Fei, Berchuck, Andrew, Anton-Culver, Hoda, Banerjee, Susana, Benitez, Javier, Bjorge, Line, Brenton, James D., Butzow, Ralf, Campbell, Ian G., Chang-Claude, Jenny, Chen, Kexin, Cook, Linda S., Cramer, Daniel W., defazio, Anna, Dennis, Joe, Doherty, Jennifer A., Doerk, Thilo, Eccles, Diana M., Edwards, Digna Velez, Fasching, Peter A., Fortner, Renee T., Gayther, Simon A., Giles, Graham G., Glasspool, Rosalind M., Goode, Ellen L., Goodman, Marc T., Gronwald, Jacek, Harris, Holly R., Heitz, Florian, Hildebrandt, Michelle A., Hogdall, Estrid, Hogdall, Claus K., Huntsman, David G., Kar, Siddhartha P., Karlan, Beth Y., Kelemen, Linda E., Kiemeney, Lambertus A., Kjaer, Susanne K., Koushik, Anita, Lambrechts, Diether, Le, Nhu D., Levine, Douglas A., Massuger, Leon F., Matsuo, Keitaro, May, Taymaa, McNeish, Iain A., Menon, Usha, Modugno, Francesmary, Monteiro, Alvaro N., Moorman, Patricia G., Moysich, Kirsten B., Ness, Roberta B., Nevanlinna, Heli, Olsson, Hakan, Onland-Moret, N. Charlotte, Park, Sue K., Paul, James, Pearce, Celeste L., Pejovic, Tanja, Phelan, Catherine M., Pike, Malcolm C., Ramus, Susan J., Riboli, Elio, Rodriguez-Antona, Cristina, Romieu, Isabelle, Sandler, Dale P., Schildkraut, Joellen M., Setiawan, Veronica W., Shan, Kang, Siddiqui, Nadeem, Sieh, Weiva, Stampfer, Meir J., Sutphen, Rebecca, Swerdlow, Anthony J., Szafron, Lukasz M., Teo, Soo Hwang, Tworoger, Shelley S., Tyrer, Jonathan P., Webb, Penelope M., Wentzensen, Nicolas, White, Emily, Willett, Walter C., Wolk, Alicja, Woo, Yin Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Chenevix-Trench, Georgia, Sellers, Thomas A., Pharoah, Paul D. P., Zheng, Wei, Long, Jirong, Yang, Yaohua, Wu, Lang, Shu, Xiang, Lu, Yingchang, Shu, Xiao-Ou, Cai, Qiuyin, Beeghly-Fadiel, Alicia, Li, Bingshan, Ye, Fei, Berchuck, Andrew, Anton-Culver, Hoda, Banerjee, Susana, Benitez, Javier, Bjorge, Line, Brenton, James D., Butzow, Ralf, Campbell, Ian G., Chang-Claude, Jenny, Chen, Kexin, Cook, Linda S., Cramer, Daniel W., defazio, Anna, Dennis, Joe, Doherty, Jennifer A., Doerk, Thilo, Eccles, Diana M., Edwards, Digna Velez, Fasching, Peter A., Fortner, Renee T., Gayther, Simon A., Giles, Graham G., Glasspool, Rosalind M., Goode, Ellen L., Goodman, Marc T., Gronwald, Jacek, Harris, Holly R., Heitz, Florian, Hildebrandt, Michelle A., Hogdall, Estrid, Hogdall, Claus K., Huntsman, David G., Kar, Siddhartha P., Karlan, Beth Y., Kelemen, Linda E., Kiemeney, Lambertus A., Kjaer, Susanne K., Koushik, Anita, Lambrechts, Diether, Le, Nhu D., Levine, Douglas A., Massuger, Leon F., Matsuo, Keitaro, May, Taymaa, McNeish, Iain A., Menon, Usha, Modugno, Francesmary, Monteiro, Alvaro N., Moorman, Patricia G., Moysich, Kirsten B., Ness, Roberta B., Nevanlinna, Heli, Olsson, Hakan, Onland-Moret, N. Charlotte, Park, Sue K., Paul, James, Pearce, Celeste L., Pejovic, Tanja, Phelan, Catherine M., Pike, Malcolm C., Ramus, Susan J., Riboli, Elio, Rodriguez-Antona, Cristina, Romieu, Isabelle, Sandler, Dale P., Schildkraut, Joellen M., Setiawan, Veronica W., Shan, Kang, Siddiqui, Nadeem, Sieh, Weiva, Stampfer, Meir J., Sutphen, Rebecca, Swerdlow, Anthony J., Szafron, Lukasz M., Teo, Soo Hwang, Tworoger, Shelley S., Tyrer, Jonathan P., Webb, Penelope M., Wentzensen, Nicolas, White, Emily, Willett, Walter C., Wolk, Alicja, Woo, Yin Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Chenevix-Trench, Georgia, Sellers, Thomas A., Pharoah, Paul D. P., Zheng, Wei, and Long, Jirong

Abstract

DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. Significance: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.

Published
2019
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221. Germline variation at 8q24 and prostate cancer risk in men of European ancestry (vol 9, 4616, 2018)

Author

Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Al Olama, Ali Amin, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Geraldine, Sorensen, Karina D., Maehle, Lovise, Grindedal, Eli M., Strom, Sara S., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Bensen, Jeanette T., Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Borge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A., Pandha, Hardev, Thibodeau, Stephen N., Schaid, Daniel J., Wiklund, Fredrik, Chanock, Stephen J., Easton, Douglas F., Eeles, Rosalind A., Kote-Jarai, Zsofia, Conti, David V., Haiman, Christopher A., Henderson, Brian E., Stern, Mariana C., Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Cook, Margaret, Fachal, Laura, Weinstein, Stephanie, Freeman, Laura E. Beane, Hoover, Robert N., Machiela, Mitchell J., Lophatananon, Artitaya, Carter, Brian D., Goodman, Phyllis, Moya, Leire, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Yeadon, Trina, Eckert, Allison, Eklund, Martin, Cavalli-Bjoerkman, Carin, Dunning, Alison M., Sipeky, Csilla, Hakansson, Niclas, Elliott, Rebecca, Ranu, Hardeep, Giovannucci, Edward, Turman, Constance, Hunter, David J., Cussenot, Olivier, Orntoft, Torben Falck, Lane, Athene, Lewis, Sarah J., Davis, Michael, Key, Tim J., Brown, Paul, Kulkarni, Girish S., Zlotta, Alexandre R., Fleshner, Neil E., Finelli, Antonio, Mao, Xueying, Marzec, Jacek, MacInnis, Robert J., Milne, Roger, Hopper, John L., Aguado, Miguel, Bustamante, Mariona, Castano-Vinyals, Gemma, Gracia-Lavedan, Esther, Cecchini, Lluis, Stampfer, Meir, Ma, Jing, Sellers, Thomas A., Geybels, Milan S., Park, Hyun, Zachariah, Babu, Kolb, Suzanne, Wokolorczyk, Dominika, Lubinski, Jan, Kluzniak, Wojciech, Nielsen, Sune F., Weisher, Maren, Cuk, Katarina, Vogel, Walther, Luedeke, Manuel, Logothetis, Christopher J., Paulo, Paula, Cardoso, Marta, Maia, Sofia, Silva, Maria P., Steele, Linda, Ding, Yuan Chun, De Meerleer, Gert, De Langhe, Sofie, Thierens, Hubert, Lim, Jasmine, Tan, Meng H., Ong, Aik T., Lin, Daniel W., Kachakova, Darina, Mitkova, Atanaska, Mitev, Vanio, Parliament, Matthew, Jenster, Guido, Bangma, Christopher, Schroder, F. H., Truong, Therese, Koudou, Yves Akoli, Michael, Agnieszka, Kierzek, Andrzej, Karlsson, Ami, Broms, Michael, Wu, Huihai, Aukim-Hastie, Claire, Tillmans, Lori, Riska, Shaun, McDonnell, Shannon K., Dearnaley, David, Spurdle, Amanda, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Papargiris, Melissa, Saunders, Pamela, Kujala, Paula, Talala, Kirsi, Taari, Kimmo, Bentzen, Soren, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, George, Anne, Toi, Ants, Evans, Andrew, van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Zhao, Shan-Chao, Ren, Guoping, Zhang, Yangling, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Pedersen, John, Lobato-Busto, Ramon, Manuel Ruiz-Dominguez, Jose, Mengual, Lourdes, Alcaraz, Antonio, Pow-Sang, Julio, Herkommer, Kathleen, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Adolfsson, Jan, Stattin, Pär, Johansson, Jan-Erik, Martin, Richard M., Thompson, Ian M., Jr., Chambers, Suzanne, Aitken, Joanne, Horvath, Lisa, Haynes, Anne-Maree, Tilley, Wayne, Risbridger, Gail, Aly, Markus, Nordstrom, Tobias, Pharoah, Paul, Tammela, Teuvo L. J., Murtola, Teemu, Auvinen, Anssi, Burnet, Neil, Barnett, Gill, Andriole, Gerald, Klim, Aleksandra, Drake, Bettina F., Borre, Michael, Kerns, Sarah, Ostrer, Harry, Zhang, Hong-Wei, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Feng, Ninghan, Li, Jie, He, Weiyang, Guo, Xin, Sun, Zan, Wang, Guomin, Guo, Jianming, Southey, Melissa C., FitzGerald, Liesel M., Marsden, Gemma, Gomez-Caamano, Antonio, Carballo, Ana, Peleteiro, Paula, Calvo, Patricia, Szulkin, Robert, Llorca, Javier, Dierssen-Sotos, Trinidad, Gomez-Acebo, Ines, Lin, Hui-Yi, Ostrander, Elaine A., Bisbjerg, Rasmus, Klarskov, Peter, Roder, Martin Andreas, Iversen, Peter, Holleczek, Bernd, Stegmaier, Christa, Schnoeller, Thomas, Bohnert, Philipp, John, Esther M., Ost, Piet, Teo, Soo-Hwang, Gamulin, Marija, Kulis, Tomislav, Kastelan, Zeljko, Slavov, Chavdar, Popov, Elenko, Van den Broeck, Thomas, Joniau, Steven, Larkin, Samantha, Esteban Castelao, Jose, Martinez, Maria Elena, van Schaik, Ron H. N., Xu, Jianfeng, Lindstrom, Sara, Riboli, Elio, Berry, Clare, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Freedman, Matthew, Cenee, Sylvie, Sanchez, Marie, Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Al Olama, Ali Amin, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Geraldine, Sorensen, Karina D., Maehle, Lovise, Grindedal, Eli M., Strom, Sara S., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Bensen, Jeanette T., Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Borge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A., Pandha, Hardev, Thibodeau, Stephen N., Schaid, Daniel J., Wiklund, Fredrik, Chanock, Stephen J., Easton, Douglas F., Eeles, Rosalind A., Kote-Jarai, Zsofia, Conti, David V., Haiman, Christopher A., Henderson, Brian E., Stern, Mariana C., Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Cook, Margaret, Fachal, Laura, Weinstein, Stephanie, Freeman, Laura E. Beane, Hoover, Robert N., Machiela, Mitchell J., Lophatananon, Artitaya, Carter, Brian D., Goodman, Phyllis, Moya, Leire, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Yeadon, Trina, Eckert, Allison, Eklund, Martin, Cavalli-Bjoerkman, Carin, Dunning, Alison M., Sipeky, Csilla, Hakansson, Niclas, Elliott, Rebecca, Ranu, Hardeep, Giovannucci, Edward, Turman, Constance, Hunter, David J., Cussenot, Olivier, Orntoft, Torben Falck, Lane, Athene, Lewis, Sarah J., Davis, Michael, Key, Tim J., Brown, Paul, Kulkarni, Girish S., Zlotta, Alexandre R., Fleshner, Neil E., Finelli, Antonio, Mao, Xueying, Marzec, Jacek, MacInnis, Robert J., Milne, Roger, Hopper, John L., Aguado, Miguel, Bustamante, Mariona, Castano-Vinyals, Gemma, Gracia-Lavedan, Esther, Cecchini, Lluis, Stampfer, Meir, Ma, Jing, Sellers, Thomas A., Geybels, Milan S., Park, Hyun, Zachariah, Babu, Kolb, Suzanne, Wokolorczyk, Dominika, Lubinski, Jan, Kluzniak, Wojciech, Nielsen, Sune F., Weisher, Maren, Cuk, Katarina, Vogel, Walther, Luedeke, Manuel, Logothetis, Christopher J., Paulo, Paula, Cardoso, Marta, Maia, Sofia, Silva, Maria P., Steele, Linda, Ding, Yuan Chun, De Meerleer, Gert, De Langhe, Sofie, Thierens, Hubert, Lim, Jasmine, Tan, Meng H., Ong, Aik T., Lin, Daniel W., Kachakova, Darina, Mitkova, Atanaska, Mitev, Vanio, Parliament, Matthew, Jenster, Guido, Bangma, Christopher, Schroder, F. H., Truong, Therese, Koudou, Yves Akoli, Michael, Agnieszka, Kierzek, Andrzej, Karlsson, Ami, Broms, Michael, Wu, Huihai, Aukim-Hastie, Claire, Tillmans, Lori, Riska, Shaun, McDonnell, Shannon K., Dearnaley, David, Spurdle, Amanda, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Papargiris, Melissa, Saunders, Pamela, Kujala, Paula, Talala, Kirsi, Taari, Kimmo, Bentzen, Soren, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, George, Anne, Toi, Ants, Evans, Andrew, van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Zhao, Shan-Chao, Ren, Guoping, Zhang, Yangling, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Pedersen, John, Lobato-Busto, Ramon, Manuel Ruiz-Dominguez, Jose, Mengual, Lourdes, Alcaraz, Antonio, Pow-Sang, Julio, Herkommer, Kathleen, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Adolfsson, Jan, Stattin, Pär, Johansson, Jan-Erik, Martin, Richard M., Thompson, Ian M., Jr., Chambers, Suzanne, Aitken, Joanne, Horvath, Lisa, Haynes, Anne-Maree, Tilley, Wayne, Risbridger, Gail, Aly, Markus, Nordstrom, Tobias, Pharoah, Paul, Tammela, Teuvo L. J., Murtola, Teemu, Auvinen, Anssi, Burnet, Neil, Barnett, Gill, Andriole, Gerald, Klim, Aleksandra, Drake, Bettina F., Borre, Michael, Kerns, Sarah, Ostrer, Harry, Zhang, Hong-Wei, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Feng, Ninghan, Li, Jie, He, Weiyang, Guo, Xin, Sun, Zan, Wang, Guomin, Guo, Jianming, Southey, Melissa C., FitzGerald, Liesel M., Marsden, Gemma, Gomez-Caamano, Antonio, Carballo, Ana, Peleteiro, Paula, Calvo, Patricia, Szulkin, Robert, Llorca, Javier, Dierssen-Sotos, Trinidad, Gomez-Acebo, Ines, Lin, Hui-Yi, Ostrander, Elaine A., Bisbjerg, Rasmus, Klarskov, Peter, Roder, Martin Andreas, Iversen, Peter, Holleczek, Bernd, Stegmaier, Christa, Schnoeller, Thomas, Bohnert, Philipp, John, Esther M., Ost, Piet, Teo, Soo-Hwang, Gamulin, Marija, Kulis, Tomislav, Kastelan, Zeljko, Slavov, Chavdar, Popov, Elenko, Van den Broeck, Thomas, Joniau, Steven, Larkin, Samantha, Esteban Castelao, Jose, Martinez, Maria Elena, van Schaik, Ron H. N., Xu, Jianfeng, Lindstrom, Sara, Riboli, Elio, Berry, Clare, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Freedman, Matthew, Cenee, Sylvie, and Sanchez, Marie

Abstract

Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-06863-1, published online 5 November 2018.

Published
2019
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222. Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations

Author

Bancroft, Elizabeth K., Saya, Sibel, Page, Elizabeth C., Myhill, Kathryn, Thomas, Sarah, Pope, Jennifer, Chamberlain, Anthony, Hart, Rachel, Glover, Wayne, Cook, Jackie, Rosario, Derek J., Helfand, Brian T., Selkirk, Christina Hutten, Davidson, Rosemarie, Longmuir, Mark, Eccles, Diana M., Gadea, Neus, Brewer, Carole, Barwell, Julian, Salinas, Monica, Greenhalgh, Lynn, Tischkowitz, Marc, Henderson, Alex, Evans, David Gareth, Buys, Saundra S., Eeles, Rosalind A., Aaronson, Neil K., Eeles, Rosalind, Bancroft, Elizabeth, Page, Elizabeth, Kote-Jarai, Zsofia, Ardern-Jones, Audrey, Bangma, Chris, Castro, Elena, Dearnaley, David, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C., Johannsson, Oskar Thor, Khoo, Vincent, Eccles, Diana, Lilja, Hans, Evans, Gareth, Eyfjord, Jorunn, Lubinski, Jan, Maehle, Lovise, Mikropoulos, Christos, Millner, Alan, Mitra, Anita, Offman, Judith, Moynihan, Clare, Rennert, Gad, Suri, Mohnish, Dias, Alex, Taylor, Natalie, D'Mello, Lucia, Pope, Jenny, James, Paul, Mitchell, Gillian, Shanley, Sue, Richardson, Kate, McKinley, Joanne, Petelin, Lara, Murphy, Morgan, Mascarenhas, Lyon, Murphy, Declan, Lam, Jimmy, Taylor, Louise, Miller, Cathy, Stapleton, Alan, Chong, Michael, Suthers, Graeme, Poplawski, Nicola, Tucker, Katherine, Andrews, Lesley, Duffy, Jessica, Millard, Richard, Ward, Robyn, Williams, Rachel, Stricker, Phillip, Kirk, Judy, Bowman, Michelle, Patel, Manish, Harris, Marion, O'Connell, Shona, Hunt, Clare, Smyth, Courtney, Frydenberg, Mark, Lindeman, Geoffrey, Shackleton, Kylie, Morton, Catherine, Susman, Rachel, McGaughran, Julie, Boon, Melanie, Pachter, Nicholas, Townshend, Sharron, Schofield, Lyn, Nicholls, Cassandra, Spigelman, Allan, Gleeson, Margaret, Amor, David, Burke, Jo, Patterson, Briony, Swindle, Peter, Scott, Rodney, Foulkes, William, Boshari, Talia, Aprikian, Armen, Jensen, Thomas, Bojeson, Anders, Osther, Palle, Skytte, Anne-Bine, Cruger, Dorthe, Tondering, Majbritt Kure, Gerdes, Anne-Marie, Schmutzler, Rita, Rhiem, Kerstin, Wihler, Petra, Kast, K., Griebsch, C., Johannsson, Oskar, Stefansdottir, Vigdis, Murthy, Vedang, Sarin, Rajiv, Awatagiri, Kasturi, Ghonge, Sujata, Kowtal, Pradnya, Mulgund, Gouri, Gallagher, David, Bambury, Richard, Farrell, Michael, Gallagher, Fergal, Kiernan, Ingrid, Friedman, Eitan, Chen-Shtoyerman, Rakefet, Basevitch, Alon, Leibovici, Dan, Melzer, Ehud, Ben-Yehoshua, Sagi Josefsberg, Nicolai, Nicola, Radice, Paolo, Valdagni, Riccardo, Magnani, Tiziana, Gay, Simona, Teo, Soo Hwang, Tan, Hui Meng, Yoon, Sook-Yee, Thong, Meow Keong, Vasen, Hans, Ringleberg, Janneke, van Asperen, Christi, Kiemeney, Bart, van Zelst-Stams, Wendy, Ausems, Margreet G. E. M., van der Luijt, Rob B., van Os, Theo, Ruijs, Marielle W. G., Adank, Muriel A., Oldenburg, Rogier A., Helderman-van den Enden, A. Paula T. J. M., Caanen, B. A. H., Oosterwijk, Jan C., Moller, Pal, Brennhovd, Bjorn, Medvik, Heidi, Hanslien, Eldbjorg, Grindedal, Eli Marie, Cybulski, Cezary, Wokolorczyk, Dominika, Teixeira, Manuel, Maia, Sofia, Peixoto, Ana, Henrique, Rui, Oliveira, Jorge, Goncalves, Nuno, Araujo, Luis, Seixas, Manuela, Souto, Joao Paulo, Nogueira, Pedro, Copakova, Lucia, Zgajnar, Janez, Krajc, Mateja, Vrecar, Alenka, Capella, Gabriel, Ramon y Cajal, Teresa, Fisas, David, Mora, Josefina, Esquena, Salvador, Balmana, Judith, Morote, Juan, Liljegren, Annelie, Hjalm-Eriksson, Marie, Ekdahl, Karl-Johan, Carlsson, Stefan, George, Angela, Kemp, Zoe, Wiggins, Jennifer, Moss, Cathryn, Van As, Nicholas, Thompson, Alan, Ogden, Chris, Woodhouse, Christopher, Kumar, Pardeep, Evans, D. Gareth, Bulman, Barbara, Rothwell, Jeanette, Tricker, Karen, Wise, Gillian, Mercer, Catherine, McBride, Donna, Costello, Philandra, Pearce, Allison, Torokwa, Audrey, Paterson, Joan, Clowes, Virginia, Taylor, Amy, Newcombe, Barbara, Walker, Lisa, Halliday, Dorothy, Stayner, Barbara, Fleming-Brown, D., Snape, Katie, Hanson, Helen, Hodgson, Shirley, Brice, Glen, Homfray, Tessa, Hammond, Carrie, Kohut, Kelly, Anjum, Uruj, Dearing, Audrey, Mencias, Mark, Potter, Alison, Renton, Caroline, Searle, Anne, Hill, Kathryn, Goodman, Selina, Garcia, Lynda, Devlin, Gemma, Everest, Sarah, Nadolski, Maria, Douglas, Fiona, Jobson, Irene, Paez, Edgar, Donaldson, Alan, Tomkins, Sue, Langman, Caroline, Jacobs, Chris, Pichert, Gabriella, Shaw, Adam, Kulkarni, Anju, Tripathi, Vishakha, Rose, Sarah, Compton, Cecilia, Watson, Michelle, Reinholtz, Cherylin, Brady, Angela, Dorkins, Huw, Melville, Athalie, Kosicka-Slawinska, Monika, Cummings, Carole, Kiesel, Vicki, Bartlett, Marion, Randhawa, Kashmir, Ellery, Natalie, Side, Lucy, Male, Alison, Simon, Kate, Rees, Katie, Tidey, Lizzie, Gurasashvili, Jana, Nevitt, Louise, Ingram, Stuart, Howell, Alice, Rosario, Derek, Catto, James, Howson, Joanne, Ong, Kai-Ren, Chapman, Cyril, Cole, Trevor, Heaton, Tricia, Hoffman, Jonathan, Burgess, Lucy, Huber, Camilla, Islam, Farah, Watt, Cathy, Duncan, Alexis, Kockelbergh, Roger, Mzazi, Shumikazi, Dineen, Amy, Sattar, Ayisha, Kaemba, Beckie, Sidat, Zahirah, Patel, Nafisa, Siguake, Kas, Birt, Angela, Poultney, Una, Umez-Eronini, Nkem, Mom, Jaswant, Sutton, Vivienne, Cornford, Philip, Bermingham, Nicola, Yesildag, Pembe, Treherne, Katy, Griffiths, Julie, Cogley, Lyn, Gott, Hannah, Rubinstein, Wendy S., Hulick, Peter, McGuire, Michael, Shevrin, Daniel, Kaul, Karen, Weissman, Scott, Newlin, Anna, Vogel, Kristen, Weiss, Shelly, Hook, Nicole, Buys, Saundra, Goldgar, David, Conner, Tom, Venne, Vickie, Stephenson, Robert, Dechet, Christopher, Domchek, Susan, Powers, Jacquelyn, Rustgi, Neil, Strom, Sara, Arun, Banu, Davis, John W., Yamamura, Yuko, Obeid, Elias, Giri, Veda, Gross, Laura, Bealin, Lisa, Cooney, Kathy, Stoffel, Elena, Okoth, Linda, Bancroft, Elizabeth K., Saya, Sibel, Page, Elizabeth C., Myhill, Kathryn, Thomas, Sarah, Pope, Jennifer, Chamberlain, Anthony, Hart, Rachel, Glover, Wayne, Cook, Jackie, Rosario, Derek J., Helfand, Brian T., Selkirk, Christina Hutten, Davidson, Rosemarie, Longmuir, Mark, Eccles, Diana M., Gadea, Neus, Brewer, Carole, Barwell, Julian, Salinas, Monica, Greenhalgh, Lynn, Tischkowitz, Marc, Henderson, Alex, Evans, David Gareth, Buys, Saundra S., Eeles, Rosalind A., Aaronson, Neil K., Eeles, Rosalind, Bancroft, Elizabeth, Page, Elizabeth, Kote-Jarai, Zsofia, Ardern-Jones, Audrey, Bangma, Chris, Castro, Elena, Dearnaley, David, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C., Johannsson, Oskar Thor, Khoo, Vincent, Eccles, Diana, Lilja, Hans, Evans, Gareth, Eyfjord, Jorunn, Lubinski, Jan, Maehle, Lovise, Mikropoulos, Christos, Millner, Alan, Mitra, Anita, Offman, Judith, Moynihan, Clare, Rennert, Gad, Suri, Mohnish, Dias, Alex, Taylor, Natalie, D'Mello, Lucia, Pope, Jenny, James, Paul, Mitchell, Gillian, Shanley, Sue, Richardson, Kate, McKinley, Joanne, Petelin, Lara, Murphy, Morgan, Mascarenhas, Lyon, Murphy, Declan, Lam, Jimmy, Taylor, Louise, Miller, Cathy, Stapleton, Alan, Chong, Michael, Suthers, Graeme, Poplawski, Nicola, Tucker, Katherine, Andrews, Lesley, Duffy, Jessica, Millard, Richard, Ward, Robyn, Williams, Rachel, Stricker, Phillip, Kirk, Judy, Bowman, Michelle, Patel, Manish, Harris, Marion, O'Connell, Shona, Hunt, Clare, Smyth, Courtney, Frydenberg, Mark, Lindeman, Geoffrey, Shackleton, Kylie, Morton, Catherine, Susman, Rachel, McGaughran, Julie, Boon, Melanie, Pachter, Nicholas, Townshend, Sharron, Schofield, Lyn, Nicholls, Cassandra, Spigelman, Allan, Gleeson, Margaret, Amor, David, Burke, Jo, Patterson, Briony, Swindle, Peter, Scott, Rodney, Foulkes, William, Boshari, Talia, Aprikian, Armen, Jensen, Thomas, Bojeson, Anders, Osther, Palle, Skytte, Anne-Bine, Cruger, Dorthe, Tondering, Majbritt Kure, Gerdes, Anne-Marie, Schmutzler, Rita, Rhiem, Kerstin, Wihler, Petra, Kast, K., Griebsch, C., Johannsson, Oskar, Stefansdottir, Vigdis, Murthy, Vedang, Sarin, Rajiv, Awatagiri, Kasturi, Ghonge, Sujata, Kowtal, Pradnya, Mulgund, Gouri, Gallagher, David, Bambury, Richard, Farrell, Michael, Gallagher, Fergal, Kiernan, Ingrid, Friedman, Eitan, Chen-Shtoyerman, Rakefet, Basevitch, Alon, Leibovici, Dan, Melzer, Ehud, Ben-Yehoshua, Sagi Josefsberg, Nicolai, Nicola, Radice, Paolo, Valdagni, Riccardo, Magnani, Tiziana, Gay, Simona, Teo, Soo Hwang, Tan, Hui Meng, Yoon, Sook-Yee, Thong, Meow Keong, Vasen, Hans, Ringleberg, Janneke, van Asperen, Christi, Kiemeney, Bart, van Zelst-Stams, Wendy, Ausems, Margreet G. E. M., van der Luijt, Rob B., van Os, Theo, Ruijs, Marielle W. G., Adank, Muriel A., Oldenburg, Rogier A., Helderman-van den Enden, A. Paula T. J. M., Caanen, B. A. H., Oosterwijk, Jan C., Moller, Pal, Brennhovd, Bjorn, Medvik, Heidi, Hanslien, Eldbjorg, Grindedal, Eli Marie, Cybulski, Cezary, Wokolorczyk, Dominika, Teixeira, Manuel, Maia, Sofia, Peixoto, Ana, Henrique, Rui, Oliveira, Jorge, Goncalves, Nuno, Araujo, Luis, Seixas, Manuela, Souto, Joao Paulo, Nogueira, Pedro, Copakova, Lucia, Zgajnar, Janez, Krajc, Mateja, Vrecar, Alenka, Capella, Gabriel, Ramon y Cajal, Teresa, Fisas, David, Mora, Josefina, Esquena, Salvador, Balmana, Judith, Morote, Juan, Liljegren, Annelie, Hjalm-Eriksson, Marie, Ekdahl, Karl-Johan, Carlsson, Stefan, George, Angela, Kemp, Zoe, Wiggins, Jennifer, Moss, Cathryn, Van As, Nicholas, Thompson, Alan, Ogden, Chris, Woodhouse, Christopher, Kumar, Pardeep, Evans, D. Gareth, Bulman, Barbara, Rothwell, Jeanette, Tricker, Karen, Wise, Gillian, Mercer, Catherine, McBride, Donna, Costello, Philandra, Pearce, Allison, Torokwa, Audrey, Paterson, Joan, Clowes, Virginia, Taylor, Amy, Newcombe, Barbara, Walker, Lisa, Halliday, Dorothy, Stayner, Barbara, Fleming-Brown, D., Snape, Katie, Hanson, Helen, Hodgson, Shirley, Brice, Glen, Homfray, Tessa, Hammond, Carrie, Kohut, Kelly, Anjum, Uruj, Dearing, Audrey, Mencias, Mark, Potter, Alison, Renton, Caroline, Searle, Anne, Hill, Kathryn, Goodman, Selina, Garcia, Lynda, Devlin, Gemma, Everest, Sarah, Nadolski, Maria, Douglas, Fiona, Jobson, Irene, Paez, Edgar, Donaldson, Alan, Tomkins, Sue, Langman, Caroline, Jacobs, Chris, Pichert, Gabriella, Shaw, Adam, Kulkarni, Anju, Tripathi, Vishakha, Rose, Sarah, Compton, Cecilia, Watson, Michelle, Reinholtz, Cherylin, Brady, Angela, Dorkins, Huw, Melville, Athalie, Kosicka-Slawinska, Monika, Cummings, Carole, Kiesel, Vicki, Bartlett, Marion, Randhawa, Kashmir, Ellery, Natalie, Side, Lucy, Male, Alison, Simon, Kate, Rees, Katie, Tidey, Lizzie, Gurasashvili, Jana, Nevitt, Louise, Ingram, Stuart, Howell, Alice, Rosario, Derek, Catto, James, Howson, Joanne, Ong, Kai-Ren, Chapman, Cyril, Cole, Trevor, Heaton, Tricia, Hoffman, Jonathan, Burgess, Lucy, Huber, Camilla, Islam, Farah, Watt, Cathy, Duncan, Alexis, Kockelbergh, Roger, Mzazi, Shumikazi, Dineen, Amy, Sattar, Ayisha, Kaemba, Beckie, Sidat, Zahirah, Patel, Nafisa, Siguake, Kas, Birt, Angela, Poultney, Una, Umez-Eronini, Nkem, Mom, Jaswant, Sutton, Vivienne, Cornford, Philip, Bermingham, Nicola, Yesildag, Pembe, Treherne, Katy, Griffiths, Julie, Cogley, Lyn, Gott, Hannah, Rubinstein, Wendy S., Hulick, Peter, McGuire, Michael, Shevrin, Daniel, Kaul, Karen, Weissman, Scott, Newlin, Anna, Vogel, Kristen, Weiss, Shelly, Hook, Nicole, Buys, Saundra, Goldgar, David, Conner, Tom, Venne, Vickie, Stephenson, Robert, Dechet, Christopher, Domchek, Susan, Powers, Jacquelyn, Rustgi, Neil, Strom, Sara, Arun, Banu, Davis, John W., Yamamura, Yuko, Obeid, Elias, Giri, Veda, Gross, Laura, Bealin, Lisa, Cooney, Kathy, Stoffel, Elena, and Okoth, Linda

Abstract

Objectives To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. Particpants and Methods Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. Results A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. Conclusion This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to me

Published
2019

223. Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study

Author

Qian, Frank, Wang, Shengfeng, Mitchell, Jonathan, McGuffog, Lesley, Barrowdale, Daniel, Leslie, Goska, Oosterwijk, Jan C., Chung, Wendy K., Evans, D. Gareth, Engel, Christoph, Kast, Karin, Aalfs, Cora M., Adank, Muriel A., Adlard, Julian, Agnarsson, Bjarni A., Aittomaki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Arun, Banu K., Ausems, Margreet G. E. M., Azzollini, Jacopo, Barouk-Simonet, Emmanuelle, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berger, Andreas, Borg, Ake, Bradbury, Angela R., Brunet, Joan, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Claes, Kathleen B. M., Collee, J. Margriet, Couch, Fergus J., Coupier, Isabelle, Daly, Mary B., Davidson, Rosemarie, Diez, Orland, Domchek, Susan M., Donaldson, Alan, Dorfling, Cecilia M., Eeles, Ros, Feliubadalo, Lidia, Foretova, Lenka, Fowler, Jeffrey, Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Garcia-Barberan, Vanesa, Glendon, Gord, Godwin, Andrew K., Gomez Garcia, Encarna B., Gronwald, Jacek, Hahnen, Eric, Hamann, Ute, Henderson, Alex, Hendricks, Carolyn B., Hopper, John L., Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, Kaczmarek, Katarzyna, Kang, Eunyoung, Karlan, Beth Y., Kets, Carolien M., Kim, Sung-Won, Kim, Zisun, Kwong, Ava, Laitman, Yael, Lasset, Christine, Lee, Min Hyuk, Lee, Jong Won, Lee, Jihyoun, Lester, Jenny, Lesueur, Fabienne, Loud, Jennifer T., Lubinski, Jan, Mebirouk, Noura, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Miller, Austin, Montagna, Marco, Mooij, Thea M., Morrison, Patrick J., Mouret-Fourme, Emmanuelle, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nielsen, Finn C., Nussbaum, Robert L., Offit, Kenneth, Olah, 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, Robson, Mark, Rodriguez, Gustavo C., Schmutzler, Rita K., Selkirk, Christina G. Hutten, Shah, Payal D., Simard, Jacques, Singer, Christian F., Sokolowska, Johanna, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E., Tucker, Katherine M., Tung, Nadine, van Asperen, Christi J., van Engelen, Klaartje, van Rensburg, Elizabeth J., Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Yannoukakos, Drakoulis, Greene, Mark H., Rookus, Matti A., Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., Goldgar, David E., Olopade, Olufunmilayo I., Rebbeck, Timothy R., Huo, Dezheng, Qian, Frank, Wang, Shengfeng, Mitchell, Jonathan, McGuffog, Lesley, Barrowdale, Daniel, Leslie, Goska, Oosterwijk, Jan C., Chung, Wendy K., Evans, D. Gareth, Engel, Christoph, Kast, Karin, Aalfs, Cora M., Adank, Muriel A., Adlard, Julian, Agnarsson, Bjarni A., Aittomaki, Kristiina, Alducci, Elisa, Andrulis, Irene L., Arun, Banu K., Ausems, Margreet G. E. M., Azzollini, Jacopo, Barouk-Simonet, Emmanuelle, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berger, Andreas, Borg, Ake, Bradbury, Angela R., Brunet, Joan, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Caputo, Sandrine M., Chiquette, Jocelyne, Claes, Kathleen B. M., Collee, J. Margriet, Couch, Fergus J., Coupier, Isabelle, Daly, Mary B., Davidson, Rosemarie, Diez, Orland, Domchek, Susan M., Donaldson, Alan, Dorfling, Cecilia M., Eeles, Ros, Feliubadalo, Lidia, Foretova, Lenka, Fowler, Jeffrey, Friedman, Eitan, Frost, Debra, Ganz, Patricia A., Garber, Judy, Garcia-Barberan, Vanesa, Glendon, Gord, Godwin, Andrew K., Gomez Garcia, Encarna B., Gronwald, Jacek, Hahnen, Eric, Hamann, Ute, Henderson, Alex, Hendricks, Carolyn B., Hopper, John L., Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, Kaczmarek, Katarzyna, Kang, Eunyoung, Karlan, Beth Y., Kets, Carolien M., Kim, Sung-Won, Kim, Zisun, Kwong, Ava, Laitman, Yael, Lasset, Christine, Lee, Min Hyuk, Lee, Jong Won, Lee, Jihyoun, Lester, Jenny, Lesueur, Fabienne, Loud, Jennifer T., Lubinski, Jan, Mebirouk, Noura, Meijers-Heijboer, Hanne E. J., Meindl, Alfons, Miller, Austin, Montagna, Marco, Mooij, Thea M., Morrison, Patrick J., Mouret-Fourme, Emmanuelle, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Nielsen, Finn C., Nussbaum, Robert L., Offit, Kenneth, Olah, 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, Robson, Mark, Rodriguez, Gustavo C., Schmutzler, Rita K., Selkirk, Christina G. Hutten, Shah, Payal D., Simard, Jacques, Singer, Christian F., Sokolowska, Johanna, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo H., Terry, Mary Beth, Thomassen, Mads, Tischkowitz, Marc, Toland, Amanda E., Tucker, Katherine M., Tung, Nadine, van Asperen, Christi J., van Engelen, Klaartje, van Rensburg, Elizabeth J., Wang-Gohrke, Shan, Wappenschmidt, Barbara, Weitzel, Jeffrey N., Yannoukakos, Drakoulis, Greene, Mark H., Rookus, Matti A., Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., Goldgar, David E., Olopade, Olufunmilayo I., Rebbeck, Timothy R., and Huo, Dezheng

Abstract

Background: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. Methods: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. Results: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m(2) increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. Conclusion: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.

Published
2019

224. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., Spurdle, Amanda B., Parsons, Michael T., Tudini, Emma, Li, Hongyan, Hahnen, Eric, Wappenschmidt, Barbara, Feliubadalo, Lidia, Aalfs, Cora M., Agata, Simona, Aittomaki, Kristiina, Alducci, Elisa, Concepcion Alonso-Cerezo, Maria, Arnold, Norbert, Auber, Bernd, Austin, Rachel, Azzollini, Jacopo, Balmana, Judith, Barbieri, Elena, Bartram, Claus R., Blanco, Ana, Bluemcke, Britta, Bonache, Sandra, Bonanni, Bernardo, Borg, Ake, Bortesi, Beatrice, Brunet, Joan, Bruzzone, Carla, Bucksch, Karolin, Cagnoli, Giulia, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A., Calvello, Mariarosaria, Capone, Gabriele L., Caputo, Sandrine M., Carnevali, Ileana, Carrasco, Estela, Caux-Moncoutier, Virginie, Cavalli, Pietro, Cini, Giulia, Clarke, Edward M., Concolino, Paola, Cops, Elisa J., Cortesi, Laura, Couch, Fergus J., Darder, Esther, de la Hoya, Miguel, Dean, Michael, Debatin, Irmgard, Del Valle, Jesus, Delnatte, Capucine, Derive, Nicolas, Diez, Orland, Ditsch, Nina, Domchek, Susan M., Dutrannoy, Veronique, Eccles, Diana M., Ehrencrona, Hans, Enders, Ute, Evans, D. Gareth, Farra, Chantal, Faust, Ulrike, Felbor, Ute, Feroce, Irene, Fine, Miriam, Foulkes, William D., Galvao, Henrique Cr, Gambino, Gaetana, Gehrig, Andrea, Gensini, Francesca, Gerdes, Anne-Marie, Germani, Aldo, Giesecke, Jutta, Gismondi, Viviana, Gomez, Carolina, Garcia, Encarna B. Gomez, Gonzalez, Sara, Grau, Elia, Grill, Sabine, Gross, Eva, Guerrieri-Gonzaga, Aliana, Guillaud-Bataille, Marine, Gutierrez-Enriquez, Sara, Haaf, Thomas, Hackmann, Karl, Hansen, Thomas Vo, Harris, Marion, Hauke, Jan, Heinrich, Tilman, Hellebrand, Heide, Herold, Karen N., Honisch, Ellen, Horvath, Judit, Houdayer, Claude, Huebbel, Verena, Iglesias, Silvia, Izquierdo, Angel, James, Paul A., Janssen, Linda Am, Jeschke, Udo, Kaulfuss, Silke, Keupp, Katharina, Kiechle, Marion, Koelbl, Alexandra, Krieger, Sophie, Kruse, Torben A., Kvist, Anders, Lalloo, Fiona, Larsen, Mirjam, Lattimore, Vanessa L., Lautrup, Charlotte, Ledig, Susanne, Leinert, Elena, Lewis, Alexandra L., Lim, Joanna, Loeffler, Markus, Lopez-Fernandez, Adria, Lucci-Cordisco, Emanuela, Maass, Nicolai, Manoukian, Siranoush, Marabelli, Monica, Matricardi, Laura, Meindl, Alfons, Michelli, Rodrigo D., Moghadasi, Setareh, Moles-Fernandez, Alejandro, Montagna, Marco, Montalban, Gemma, Monteiro, Alvaro N., Montes, Eva, Mori, Luigi, Moserle, Lidia, Mueller, Clemens R., Mundhenke, Christoph, Naldi, Nadia, Nathanson, Katherine L., Navarro, Matilde, Nevanlinna, Heli, Nichols, Cassandra B., Niederacher, Dieter, Nielsen, Henriette R., Ong, Kai-ren, Pachter, Nicholas, Palmero, Edenir, I, Papi, Laura, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Pfeifer, Katharina, Pineda, Marta, Pohl-Rescigno, Esther, Poplawski, Nicola K., Porfirio, Berardino, Quante, Anne S., Ramser, Juliane, Reis, Rui M., Revillion, Francoise, Rhiem, Kerstin, Riboli, Barbara, Ritter, Julia, Rivera, Daniela, Rofes, Paula, Rump, Andreas, Salinas, Monica, Sanchez de Abajo, Ana Maria, Schmidt, Gunnar, Schoenwiese, Ulrike, Seggewiss, Jochen, Solanes, Ares, Steinemann, Doris, Stiller, Mathias, Stoppa-Lyonnet, Dominique, Sullivan, Kelly J., Susman, Rachel, Sutter, Christian, Tavtigian, Sean, V, Teo, Soo H., Teule, Alex, Thomassen, Mads, Tibiletti, Maria Grazia, Tischkowitz, Marc, Tognazzo, Silvia, Toland, Amanda E., Tornero, Eva, Torngren, Therese, Torres-Esquius, Sara, Toss, Angela, Trainer, Alison H., Tucker, Katherine M., van Asperen, Christi J., van Mackelenbergh, Marion T., Varesco, Liliana, Vargas-Parra, Gardenia, Varon, Raymonda, Vega, Ana, Velasco, Angela, Vesper, Anne-Sophie, Viel, Alessandra, Vreeswijk, Maaike P. G., Wagner, Sebastian A., Waha, Anke, Walker, Logan C., Walters, Rhiannon J., Wang-Gohrke, Shan, Weber, Bernhard H. F., Weichert, Wilko, Wieland, Kerstin, Wiesmueller, Lisa, Witzel, Isabell, Woeckel, Achim, Woodward, Emma R., Zachariae, Silke, Zampiga, Valentina, Zeder-Goss, Christine, Lazaro, Conxi, De Nicolo, Arcangela, Radice, Paolo, Engel, Christoph, Schmutzler, Rita K., Goldgar, David E., and Spurdle, Amanda B.

Abstract

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification.

Published
2019

225. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers

Author

Page, Elizabeth C., Bancroft, Elizabeth K., Brook, Mark N., Assel, Melissa, Al Battat, Mona Hassan, Thomas, Sarah, Taylor, Natalie, Chamberlain, Anthony, Pope, Jennifer, Ni Raghallaigh, Holly, Evans, D. Gareth, Rothwell, Jeanette, Maehle, Lovise, Grindedal, Eli Marie, James, Paul, Mascarenhas, Lyon, McKinley, Joanne, Side, Lucy, Thomas, Tessy, van Asperen, Christi, Vasen, Hans, Kiemeney, Lambertus A., Ringelberg, Janneke, Jensen, Thomas Dyrso, Osther, Palle J. S., Helfand, Brian T., Genova, Elena, Oldenburg, Rogier A., Cybulski, Cezary, Wokolorczyk, Dominika, Ong, Kai-Ren, Huber, Camilla, Lam, Jimmy, Taylor, Louise, Salinas, Monica, Feliubadalo, Lidia, Oosterwijk, Jan C., van Zelst-Stams, Wendy, Cook, Jackie, Rosario, Derek J., Domchek, Susan, Powers, Jacquelyn, Buys, Saundra, O'Toole, Karen, Ausems, Margreet G. E. M., Schmutzler, Rita K., Rhiem, Kerstin, Izatt, Louise, Tripathi, Vishakha, Teixeira, Manuel R., Cardoso, Marta, Foulkes, William D., Aprikian, Armen, van Randeraad, Heleen, Davidson, Rosemarie, Longmuir, Mark, Ruijs, Marielle W. G., Helderman van den Enden, Apollonia T. J. M., Adank, Muriel, Williams, Rachel, Andrews, Lesley, Murphy, Declan G., Halliday, Dorothy, Walker, Lisa, Liljegren, Annelie, Carlsson, Stefan, Azzabi, Ashraf, Jobson, Irene, Morton, Catherine, Shackleton, Kylie, Snape, Katie, Hanson, Helen, Harris, Marion, Tischkowitz, Marc, Taylor, Amy, Kirk, Judy, Susman, Rachel, Chen-Shtoyerman, Rakefet, Spigelman, Allan, Pachter, Nicholas, Ahmed, Munaza, Ramon y Cajal, Teresa, Zgajnar, Janez, Brewer, Carole, Gadea, Neus, Brady, Angela F., van Os, Theo, Gallagher, David, Johannsson, Oskar, Donaldson, Alan, Barwell, Julian, Nicolai, Nicola, Friedman, Eitan, Obeid, Elias, Greenhalgh, Lynn, Murthy, Vedang, Copakova, Lucia, Saya, Sibel, McGrath, John, Cooke, Peter, Ronlund, Karina, Richardson, Kate, Henderson, Alex, Teo, Soo H., Arun, Banu, Kast, Karin, Dias, Alexander, Aaronson, Neil K., Ardern-Jones, Audrey, Bangma, Chris H., Castro, Elena, Dearnaley, David, Eccles, Diana M., Tricker, Karen, Eyfjord, Jorunn, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C., Stefansdottir, Vigdis, Khoo, Vincent, Lindeman, Geoffrey J., Lubinski, Jan, Axcrona, Karol, Mikropoulos, Christos, Mitra, Anita, Moynihan, Clare, Rennert, Gadi, Suri, Mohnish, Wilson, Penny, Dudderidge, Tim, Offman, Judith, Kote-Jarai, Zsofia, Vickers, Andrew, Lilja, Hans, Eeles, Rosalind A., Page, Elizabeth C., Bancroft, Elizabeth K., Brook, Mark N., Assel, Melissa, Al Battat, Mona Hassan, Thomas, Sarah, Taylor, Natalie, Chamberlain, Anthony, Pope, Jennifer, Ni Raghallaigh, Holly, Evans, D. Gareth, Rothwell, Jeanette, Maehle, Lovise, Grindedal, Eli Marie, James, Paul, Mascarenhas, Lyon, McKinley, Joanne, Side, Lucy, Thomas, Tessy, van Asperen, Christi, Vasen, Hans, Kiemeney, Lambertus A., Ringelberg, Janneke, Jensen, Thomas Dyrso, Osther, Palle J. S., Helfand, Brian T., Genova, Elena, Oldenburg, Rogier A., Cybulski, Cezary, Wokolorczyk, Dominika, Ong, Kai-Ren, Huber, Camilla, Lam, Jimmy, Taylor, Louise, Salinas, Monica, Feliubadalo, Lidia, Oosterwijk, Jan C., van Zelst-Stams, Wendy, Cook, Jackie, Rosario, Derek J., Domchek, Susan, Powers, Jacquelyn, Buys, Saundra, O'Toole, Karen, Ausems, Margreet G. E. M., Schmutzler, Rita K., Rhiem, Kerstin, Izatt, Louise, Tripathi, Vishakha, Teixeira, Manuel R., Cardoso, Marta, Foulkes, William D., Aprikian, Armen, van Randeraad, Heleen, Davidson, Rosemarie, Longmuir, Mark, Ruijs, Marielle W. G., Helderman van den Enden, Apollonia T. J. M., Adank, Muriel, Williams, Rachel, Andrews, Lesley, Murphy, Declan G., Halliday, Dorothy, Walker, Lisa, Liljegren, Annelie, Carlsson, Stefan, Azzabi, Ashraf, Jobson, Irene, Morton, Catherine, Shackleton, Kylie, Snape, Katie, Hanson, Helen, Harris, Marion, Tischkowitz, Marc, Taylor, Amy, Kirk, Judy, Susman, Rachel, Chen-Shtoyerman, Rakefet, Spigelman, Allan, Pachter, Nicholas, Ahmed, Munaza, Ramon y Cajal, Teresa, Zgajnar, Janez, Brewer, Carole, Gadea, Neus, Brady, Angela F., van Os, Theo, Gallagher, David, Johannsson, Oskar, Donaldson, Alan, Barwell, Julian, Nicolai, Nicola, Friedman, Eitan, Obeid, Elias, Greenhalgh, Lynn, Murthy, Vedang, Copakova, Lucia, Saya, Sibel, McGrath, John, Cooke, Peter, Ronlund, Karina, Richardson, Kate, Henderson, Alex, Teo, Soo H., Arun, Banu, Kast, Karin, Dias, Alexander, Aaronson, Neil K., Ardern-Jones, Audrey, Bangma, Chris H., Castro, Elena, Dearnaley, David, Eccles, Diana M., Tricker, Karen, Eyfjord, Jorunn, Falconer, Alison, Foster, Christopher, Gronberg, Henrik, Hamdy, Freddie C., Stefansdottir, Vigdis, Khoo, Vincent, Lindeman, Geoffrey J., Lubinski, Jan, Axcrona, Karol, Mikropoulos, Christos, Mitra, Anita, Moynihan, Clare, Rennert, Gadi, Suri, Mohnish, Wilson, Penny, Dudderidge, Tim, Offman, Judith, Kote-Jarai, Zsofia, Vickers, Andrew, Lilja, Hans, and Eeles, Rosalind A.

Abstract

Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. Design, setting, and participants: Men aged 40-69 yr with a germline pathogenic BRCA1/ 2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA> 3.0 ng/ml, men were offered prostate biopsy. Outcome measurements and statistical analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. Results and limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p= 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biop

Published
2019

226. Measurement challenge: protocol for international case–control comparison of mammographic measures that predict breast cancer risk

Author

Dench, Evenda, Bond-smith, Daniela, Darcey, Ellie, Lee, Grant, Aung, Ye K, Chan, Ariane, Cuzick, Jack, Ding, Ze Y, Evans, Chris F, Harvey, Jennifer, Highnam, Ralph, Hsieh, Meng-kang, Kontos, Despina, Li, Shuai, Mariapun, Shivaani, Nickson, Carolyn, Nguyen, Tuong L, Pertuz, Said, Procopio, Pietro, Rajaram, Nadia, Repich, Kathy, Tan, Maxine, Teo, Soo-hwang, Trinh, Nhut Ho, Ursin, Giske, Wang, Chao, Dos-santos-silva, Isabel, Mccormack, Valerie, Nielsen, Mads, Shepherd, John, Hopper, John L, Stone, Jennifer, Dench, Evenda, Bond-smith, Daniela, Darcey, Ellie, Lee, Grant, Aung, Ye K, Chan, Ariane, Cuzick, Jack, Ding, Ze Y, Evans, Chris F, Harvey, Jennifer, Highnam, Ralph, Hsieh, Meng-kang, Kontos, Despina, Li, Shuai, Mariapun, Shivaani, Nickson, Carolyn, Nguyen, Tuong L, Pertuz, Said, Procopio, Pietro, Rajaram, Nadia, Repich, Kathy, Tan, Maxine, Teo, Soo-hwang, Trinh, Nhut Ho, Ursin, Giske, Wang, Chao, Dos-santos-silva, Isabel, Mccormack, Valerie, Nielsen, Mads, Shepherd, John, Hopper, John L, and Stone, Jennifer

Published
2019

227. Polygenic risk modeling for prediction of epithelial ovarian cancer risk

Author

Dareng, Eileen O., Tyrer, Jonathan P., Barnes, Daniel R., Jones, Michelle R., Yang, Xin, Aben, Katja K. H., Adank, Muriel A., Agata, Simona, Andrulis, Irene L., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Arun, Banu K., Augustinsson, Annelie, Balmaña, Judith, Bandera, Elisa V., Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bermisheva, Marina, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bonanni, Bernardo, Borg, Ake, Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Buys, Saundra S., Cai, Hui, Caligo, Maria A., Campbell, Ian, Cannioto, Rikki, Cassingham, Hayley, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chiew, Yoke-Eng, Chung, Wendy K., Claes, Kathleen B. M., Colonna, Sarah, Cook, Linda S., Couch, Fergus J., Daly, Mary B., Dao, Fanny, Davies, Eleanor, de la Hoya, Miguel, de Putter, Robin, Dennis, Joe, DePersia, Allison, Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Doherty, Jennifer A., Domchek, Susan M., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Eliassen, Heather A., Engel, Christoph, Evans, Gareth D., Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Machackova, Eva, Friedman, Eitan, Ganz, Patricia A., Garber, Judy, Gensini, Francesca, Giles, Graham G., Glendon, Gord, Godwin, Andrew K., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Hahnen, Eric, Haiman, Christopher A., Håkansson, Niclas, Hamann, Ute, Hansen, Thomas V. O., Harris, Holly R., Hartman, Mikael, Heitz, Florian, Hildebrandt, Michelle A. T., Høgdall, Estrid, Høgdall, Claus K., Hopper, John L., Huang, Ruea-Yea, Huff, Chad, Hulick, Peter J., Huntsman, David G., Imyanitov, Evgeny N., Isaacs, Claudine, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, Jensen, Allan, Johannsson, Oskar Th., John, Esther M., Jones, Michael E., Kang, Daehee, Karlan, Beth Y., Karnezis, Anthony, Kelemen, Linda E., Khusnutdinova, Elza, Kiemeney, Lambertus A., Kim, Byoung-Gie, Kjaer, Susanne K., Komenaka, Ian, Kupryjanczyk, Jolanta, Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Larson, Melissa C., Lazaro, Conxi, Le, Nhu D., Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Levine, Douglas A., Li, Lian, Li, Jingmei, Loud, Jennifer T., Lu, Karen H., Lubiński, Jan, Mai, Phuong L., Manoukian, Siranoush, Marks, Jeffrey R., Matsuno, Rayna Kim, Matsuo, Keitaro, May, Taymaa, McGuffog, Lesley, McLaughlin, John R., McNeish, Iain A., Mebirouk, Noura, Menon, Usha, Miller, Austin, Milne, Roger L., Minlikeeva, Albina, Modugno, Francesmary, Montagna, Marco, Moysich, Kirsten B., Munro, Elizabeth, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nielsen, Henriette Roed, Nielsen, Finn C., Nikitina-Zake, Liene, Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olbrecht, Siel, Olopade, Olufunmilayo I., Olson, Sara H., Olsson, Håkan, Osorio, Ana, Papi, Laura, Park, Sue K., Parsons, Michael T., Pathak, Harsha, Pedersen, Inge Sokilde, Peixoto, Ana, Pejovic, Tanja, Perez-Segura, Pedro, Permuth, Jennifer B., Peshkin, Beth, Peterlongo, Paolo, Piskorz, Anna, Prokofyeva, Darya, Radice, Paolo, Rantala, Johanna, Riggan, Marjorie J., Risch, Harvey A., Rodriguez-Antona, Cristina, Ross, Eric, Rossing, Mary Anne, Runnebaum, Ingo, Sandler, Dale P., Santamariña, Marta, Soucy, Penny, Schmutzler, Rita K., Setiawan, V. Wendy, Shan, Kang, Sieh, Weiva, Simard, Jacques, Singer, Christian F., Sokolenko, Anna P., Song, Honglin, Southey, Melissa C., Steed, Helen, Stoppa-Lyonnet, Dominique, Sutphen, Rebecca, Swerdlow, Anthony J., Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Thompson, Pamela J., Thomsen, Liv Cecilie Vestrheim, Thull, Darcy L., Tischkowitz, Marc, Titus, Linda, Toland, Amanda E., Torres, Diana, Trabert, Britton, Travis, Ruth, Tung, Nadine, Tworoger, Shelley S., Valen, Ellen, van Altena, Anne M., van der Hout, Annemieke H., Van Nieuwenhuysen, Els, van Rensburg, Elizabeth J., Vega, Ana, Edwards, Digna Velez, Vierkant, Robert A., Wang, Frances, Wappenschmidt, Barbara, Webb, Penelope M., Weinberg, Clarice R., Weitzel, Jeffrey N., Wentzensen, Nicolas, White, Emily, Whittemore, Alice S., Winham, Stacey J., Wolk, Alicja, Woo, Yin-Ling, Wu, Anna H., Yan, Li, Yannoukakos, Drakoulis, Zavaglia, Katia M., Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Kleibl, Zdenek, Easton, Douglas, Lawrenson, Kate, DeFazio, Anna, Sellers, Thomas A., Ramus, Susan J., Pearce, Celeste L., Monteiro, Alvaro N., Cunningham, Julie, Goode, Ellen L., Schildkraut, Joellen M., Berchuck, Andrew, Chenevix-Trench, Georgia, Gayther, Simon A., Antoniou, Antonis C., and Pharoah, Paul D. P.

Abstract

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1and 12,337 BRCA2pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.

Published
2022
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228. Communication about positive BRCA1 and BRCA2 genetic test results and uptake of testing in relatives in a diverse Asian setting.

Author

Lee, Daphne S.‐C., Meiser, Bettina, Mariapun, Shivaani, Hassan, Tiara, Yip, Cheng‐Har, Mohd Taib, Nur A., Teo, Soo‐Hwang, Thong, Meow‐Keong, and Yoon, Sook‐Yee

Abstract

The vast majority of studies assessing communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have been conducted in Western societies, and a dearth of studies have been conducted in Asia among relatives of diverse carriers of pathogenic BRCA1/2 germline variants. This study aimed to present rates of BRCA1/2 result disclosure by probands and probands' motivators and barriers of family communication and predictive testing uptake among eligible relatives. It also examined patterns of disclosure and testing uptake among different types of relatives. Eighty‐seven carriers with either breast or ovarian cancer, who had previously been found to be carriers of a pathogenic variant in BRCA1/2, were interviewed over the phone using a semi‐structured interview guide. Fifty‐six percent of patients were Chinese, 21% were Indian, and 23% were Malay. It was found that 62.0% of eligible first‐ and second‐degree relatives were informed by the proband about the testing result and that 11.5% of eligible first‐ and second‐degree relatives had genetic testing. First‐degree relatives were more likely to have been informed and tested compared to second‐degree relatives, as were sisters compared to brothers. The low rates of family communication and testing uptake documented in this study suggest that interventions should focus on encouraging probands to inform male and second‐degree relatives and targeting such relatives to increase informed decisions and accessibility to testing. Promotion strategies should be culturally sensitive to optimize outcomes. [ABSTRACT FROM AUTHOR]

Published
2021
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229. Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Author

Matejcic, Marco, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Wang, Kan, Sheng, Xin, Olama, Ali Amin Al, Schumacher, Fredrick R., Ingles, Sue A., Govindasami, Koveela, Benlloch, Sara, Berndt, Sonja I., Albanes, Demetrius, Koutros, Stella, Muir, Kenneth, Stevens, Victoria L., Gapstur, Susan M., Tangen, Catherine M., Batra, Jyotsna, Clements, Judith, Grönberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Wolk, Alicja, West, Catharine, Mucci, Lorelei, Kraft, Peter, Cancel-Tassin, Géraldine, Sorensen, Karina D., Maehle, Lovise, Grindedal, Eli M., Strom, Sara S., Neal, David E., Hamdy, Freddie C., Donovan, Jenny L., Travis, Ruth C., Hamilton, Robert J., Rosenstein, Barry, Lu, Yong-Jie, Giles, Graham G., Kibel, Adam S., Vega, Ana, Bensen, Jeanette T., Kogevinas, Manolis, Penney, Kathryn L., Park, Jong Y., Stanford, Janet L., Cybulski, Cezary, Nordestgaard, Børge G., Brenner, Hermann, Maier, Christiane, Kim, Jeri, Teixeira, Manuel R., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Lessel, Davor, Kaneva, Radka, Usmani, Nawaid, Claessens, Frank, Townsend, Paul A., Gago-Dominguez, Manuela, Roobol, Monique J., Menegaux, Florence, Khaw, Kay-Tee, Cannon-Albright, Lisa A., Pandha, Hardev, Thibodeau, Stephen N., Schaid, Daniel J., Henderson, Brian E., Stern, Mariana C., Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Cook, Margaret, Fachal, Laura, Weinstein, Stephanie, Beane Freeman, Laura E., Hoover, Robert N., Machiela, Mitchell J., Lophatananon, Artitaya, Carter, Brian D., Goodman, Phyllis J., Moya, Leire, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Yeadon, Trina, Eckert, Allison, Eklund, Martin, Cavalli-Bjoerkman, Carin, Dunning, Alison M., Sipeky, Csilla, Hakansson, Niclas, Elliott, Rebecca, Ranu, Hardeep, Giovannucci, Edward, Turman, Constance, Hunter, David J., Cussenot, Olivier, Orntoft, Torben Falck, Lane, Athene, Lewis, Sarah J., Davis, Michael, Key, Tim J., Brown, Paul, Kulkarni, Girish S., Zlotta, Alexandre R., Fleshner, Neil E., Finelli, Antonio, Mao, Xueying, Marzec, Jacek, MacInnis, Robert J., Milne, Roger, Hopper, John L., Aguado, Miguel, Bustamante, Mariona, Castaño-Vinyals, Gemma, Gracia-Lavedan, Esther, Cecchini, Lluís, Stampfer, Meir, Ma, Jing, Sellers, Thomas A., Geybels, Milan S., Park, Hyun, Zachariah, Babu, Kolb, Suzanne, Wokolorczyk, Dominika, Lubinski, Jan, Kluzniak, Wojciech, Nielsen, Sune F., Weisher, Maren, Cuk, Katarina, Vogel, Walther, Luedeke, Manuel, Logothetis, Christopher J. J., Paulo, Paula, Cardoso, Marta, Maia, Sofia, Silva, Maria P., Steele, Linda, Ding, Yuan Chun, De Meerleer, Gert, De Langhe, Sofie, Thierens, Hubert, Lim, Jasmine, Tan, Meng H., Ong, Aik T., Lin, Daniel W., Kachakova, Darina, Mitkova, Atanaska, Mitev, Vanio, Parliament, Matthew, Jenster, Guido, Bangma, Christopher, Schroder, F. H., Truong, Thérèse, Koudou, Yves Akoli, Michael, Agnieszka, Kierzek, Andrzej, Karlsson, Ami, Broms, Michael, Wu, Huihai, Aukim-Hastie, Claire, Tillmans, Lori, Riska, Shaun, McDonnell, Shannon K., Dearnaley, David, Spurdle, Amanda, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Papargiris, Melissa, Saunders, Pamela, Kujala, Paula, Talala, Kirsi, Taari, Kimmo, Bentzen, Søren, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, George, Anne, Toi, Ants, Evans, Andrew, van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Zhao, Shan-Chao, Ren, Guoping, Zhang, Yangling, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Pedersen, John, Lobato-Busto, Ramón, Ruiz-Dominguez, José Manuel, Mengual, Lourdes, Alcaraz, Antonio, Pow-Sang, Julio, Herkommer, Kathleen, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Adolfsson, Jan, Stattin, Par, Johansson, Jan-Erik, Martin, Richard M., Thompson, Ian M., Chambers, Suzanne, Aitken, Joanne, Horvath, Lisa, Haynes, Anne-Maree, Tilley, Wayne, Risbridger, Gail, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Tammela, Teuvo L. J., Murtola, Teemu, Auvinen, Anssi, Burnet, Neil, Barnett, Gill, Andriole, Gerald, Klim, Aleksandra, Drake, Bettina F., Borre, Michael, Kerns, Sarah, Ostrer, Harry, Zhang, Hong-Wei, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Feng, Ninghan, Li, Jie, He, Weiyang, Guo, Xin, Sun, Zan, Wang, Guomin, Guo, Jianming, Southey, Melissa C., Fitzgerald, Liesel M., Marsden, Gemma, Gómez-Caamaño, Antonio, Carballo, Ana, Peleteiro, Paula, Calvo, Patricia, Szulkin, Robert, Llorca, Javier, Dierssen-Sotos, Trinidad, Gómez Acebo, Inés, Lin, Hui-Yi, Ostrander, Elaine A., Bisbjerg, Rasmus, Klarskov, Peter, Røder, Martin Andreas, Iversen, Peter, Holleczek, Bernd, Stegmaier, Christa, Schnoeller, Thomas, Bohnert, Philipp, John, Esther M., Ost, Piet, Teo, Soo-Hwang, Gamulin, Marija, Kulis, Tomislav, Kastelan, Zeljko, Slavov, Chavdar, Popov, Elenko, Van den Broeck, Thomas, Joniau, Steven, Larkin, Samantha, Castelao, Jose Esteban, Martinez, Maria Elena, van Schaik, Ron H. N., Xu, Jianfeng, Lindström, Sara, Riboli, Elio, Berry, Clare, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Freedman, Matthew, Cenee, Sylvie, Sanchez, Marie, Wiklund, Fredrik, Chanock, Stephen J., Easton, Douglas F., Eeles, Rosalind A., Kote-Jarai, Zsofia, Conti, David V., Haiman, Christopher A., Universidad de Cantabria, De Meerleer, Gert, Keck School of Medicine [Los Angeles], University of Southern California (USC), The institute of cancer research [London], Department of Clinical Neurosciences [Cambridge], University of Cambridge [UK] (CAM), Centre for Cancer Genetic Epidemiology [Cambridge], Department of Oncology-University of Cambridge [UK] (CAM), Case Western Reserve University [Cleveland], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Warwick Medical School, University of Warwick [Coventry], University of Manchester [Manchester], Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University College of London [London] (UCL), University of Turku, University of Tampere [Finland], The Institute of Environmental Medicine [Stockholm] (IMM), Manchester Academic Health Science Centre (MAHSC), Harvard School of Public Health, Harvard T.H. Chan School of Public Health, Université Pierre et Marie Curie - Paris 6 (UPMC), Aarhus University Hospital, Aarhus University [Aarhus], Oslo University Hospital [Oslo], The University of Texas M.D. Anderson Cancer Center [Houston], Addenbrooke's Hospital, Cambridge University NHS Trust, University of Oxford [Oxford], School of Social and Community Medicine [Bristol], University of Bristol [Bristol], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Centre for Molecular Oncology and Imaging, Centre for Molecular Oncology and Imaging, Barts Cancer Institute, Queen Mary University of London (QMUL), University of Melbourne, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), CIBER de Enfermedades Raras (CIBERER), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, CIBER de Epidemiología y Salud Pública (CIBERESP), IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), University of Washington [Seattle], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), National Center for Tumor Diseases [Dresden] (NCT), Technische Universität Dresden = Dresden University of Technology (TU Dresden)-German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Universität Ulm - Ulm University [Ulm, Allemagne], Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto, Universiteit Gent = Ghent University [Belgium] (UGENT), University of Malaya [Kuala Lumpur, Malaisie], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University of Alberta, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University of California [San Diego] (UC San Diego), University of California, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, University of Utah School of Medicine [Salt Lake City], University of Surrey (UNIS), Mayo Clinic [Rochester], Royal Marsden NHS Foundation Trust, Dadaev, Tokhir [0000-0002-8268-0438], Brook, Mark N [0000-0002-8969-2378], Wang, Kan [0000-0002-0640-6058], Olama, Ali Amin Al [0000-0002-7178-3431], Schumacher, Fredrick R [0000-0002-3073-7463], Muir, Kenneth [0000-0001-6429-988X], Batra, Jyotsna [0000-0003-4646-6247], Pashayan, Nora [0000-0003-0843-2468], Schleutker, Johanna [0000-0002-1863-0305], Wolk, Alicja [0000-0001-7387-6845], Cancel-Tassin, Géraldine [0000-0002-9583-6382], Sorensen, Karina D [0000-0002-4902-5490], Lessel, Davor [0000-0003-4496-244X], Roobol, Monique J [0000-0001-6967-1708], Chanock, Stephen J [0000-0002-2324-3393], Easton, Douglas F [0000-0003-2444-3247], Eeles, Rosalind A [0000-0002-3698-6241], Apollo - University of Cambridge Repository, University of Cambridge [UK] (CAM)-Department of Oncology, University of Oxford, Universidade do Porto = University of Porto, Universiteit Gent = Ghent University (UGENT), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), University of California (UC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Gestionnaire, Hal Sorbonne Université, Urology, University Management, Clinicum, and HUS Abdominal Center

Subjects
0301 basic medicine, Oncology, Male, [SDV]Life Sciences [q-bio], LOCI, General Physics and Astronomy, Genome-wide association study, PROGRESSION, [SDV.GEN] Life Sciences [q-bio]/Genetics, MYC, SUSCEPTIBILITY, UP-REGULATION, Prostate cancer, Risk Factors, Genotype, Urologi och njurmedicin, Medicine, lcsh:Science, Pròstata -- Càncer, education.field_of_study, RARE VARIANT, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Manchester Cancer Research Centre, LONG NONCODING RNA, Chromosome Mapping, Men, 3. Good health, [SDV] Life Sciences [q-bio], Multidisciplinary Sciences, Science & Technology - Other Topics, Disease Susceptibility, Risk assessment, Chromosomes, Human, Pair 8, Genetic Markers, medicine.medical_specialty, Science, 3122 Cancers, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Article, General Biochemistry, Genetics and Molecular Biology, White People, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, SDG 3 - Good Health and Well-being, Internal medicine, Genetics, Urology and Nephrology, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, Author Correction, METAANALYSIS, [SDV.GEN]Life Sciences [q-bio]/Genetics, Cancer och onkologi, Science & Technology, Càncer de pròstata, business.industry, ResearchInstitutes_Networks_Beacons/mcrc, Case-control study, Cancer, Prostatic Neoplasms, General Chemistry, 3126 Surgery, anesthesiology, intensive care, radiology, medicine.disease, 030104 developmental biology, Homes, Haplotypes, Cancer and Oncology, Case-Control Studies, lcsh:Q, Population Risk, business, Genètica, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p, Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.

Published
2018

230. The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity

Author

Colombo, Mara, Lòpez-Perolio, Irene, Meeks, Huong D, Caleca, Laura, Parsons, Michael T, Li, Hongyan, De Vecchi, Giovanna, Tudini, Emma, Foglia, Claudia, Mondini, Patrizia, Manoukian, Siranoush, Behar, Raquel, Garcia, Encarna B Gómez, Meindl, Alfons, Montagna, Marco, Niederacher, Dieter, Schmidt, Ane Y, Varesco, Liliana, Wappenschmidt, Barbara, Bolla, Manjeet K, Dennis, Joe, Michailidou, Kyriaki, Wang, Qin, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Beckmann, Matthias W, Beeghly-Fadel, Alicia, Benitez, Javier, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Chang-Claude, Jenny, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Devilee, Peter, Dörk, Thilo, Eriksson, Mikael, Fasching, Peter A, Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Gabrielson, Marike, García-Closas, Montserrat, Giles, Graham G, González-Neira, Anna, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Hartman, Mikael, Hauke, Jan, Hollestelle, Antoinette, Hopper, John L, Jakubowska, Anna, Jung, Audrey, Kosma, Veli-Matti, Lambrechts, Diether, Le Marchand, Loid, Lindblom, Annika, Lubinski, Jan, Mannermaa, Arto, Margolin, Sara, Miao, Hui, Milne, Roger L, Neuhausen, Susan L, Nevanlinna, Heli, Olson, Janet E, Peterlongo, Paolo, Peto, Julian, Pylkäs, Katri, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Schneeweiss, Andreas, Schoemaker, Minouk J, See, Mee Hoong, Southey, Melissa C, Swerdlow, Anthony, Teo, Soo H, Toland, Amanda E, Tomlinson, Ian, Truong, Thérèse, Van Asperen, Christi J, Van Den Ouweland, Ans MW, Van Der Kolk, Lizet E, Winqvist, Robert, Yannoukakos, Drakoulis, Zheng, Wei, KConFab/AOCS Investigators, Dunning, Alison M, Easton, Douglas F, Henderson, Alex, Hogervorst, Frans BL, Izatt, Louise, Offitt, Kenneth, Side, Lucy E, Van Rensburg, Elizabeth J, Embrace, Study, Hebon, Study, McGuffog, Lesley, Antoniou, Antonis C, Chenevix-Trench, Georgia, Spurdle, Amanda B, Goldgar, David E, Hoya, Miguel De La, and Radice, Paolo

Subjects
BRCA2 Protein, Base Sequence, Models, Genetic, digital PCR, multifactorial likelihood analysis, spliceogenic variants, Mitomycin, RNA Splicing, Genetic Variation, Exons, BRCA2, Cell Line, Calibration, Humans, Female, Genetic Predisposition to Disease, quantitative real-time PCR, RNA, Messenger
Abstract

Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR (dPCR), the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10-115 . There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24) nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the nonpathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants.

Published
2018
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231. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations

Author

Rebbeck, Timothy R, Friebel, Tara M, Friedman, Eitan, Hamann, Ute, Huo, Dezheng, Kwong, Ava, Olah, Edith, Olopade, Olufunmilayo I, Solano, Angela 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 Kyung, Torres, Diana, van Rensburg, Elizabeth J, McGuffog, Lesley, Parsons, Michael T, Leslie, Goska, Aalfs, Cora M, Abugattas, Julio, Adlard, Julian, Agata, Simona, Aittomäki, Kristiina, Andrews, Lesley, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Arun, Banu K, Asseryanis, Ella, Auerbach, Leo, Azzollini, Jacopo, Balmaña, Judith, Barile, Monica, Barkardottir, Rosa B, Barrowdale, Daniel, Benitez, Javier, Berger, Andreas, Berger, Raanan, Blanco, Amie M, Blazer, Kathleen R, Blok, Marinus J, Bonadona, Valérie, Bonanni, Bernardo, Bradbury, Angela R, Brewer, Carole, Buecher, Bruno, Buys, Saundra S, Caldes, Trinidad, Caliebe, Almuth, Caligo, Maria A, Campbell, Ian, Caputo, Sandrine M, Chiquette, Jocelyne, Chung, Wendy K, Claes, Kathleen BM, Collée, J Margriet, Cook, Jackie, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Pauw, Antoine, Delnatte, Capucine, Diez, Orland, Ding, Yuan Chun, Ditsch, Nina, Domchek, Susan M, Dorfling, Cecilia M, Velazquez, Carolina, Dworniczak, Bernd, Eason, Jacqueline, Easton, Douglas F, Eeles, Ros, Ehrencrona, Hans, Ejlertsen, Bent, EMBRACE, Engel, Christoph, Engert, Stefanie, Evans, D Gareth, Faivre, Laurence, Feliubadaló, Lidia, Ferrer, Sandra Fert, Foretova, Lenka, Fowler, Jeffrey, Frost, Debra, Galvão, Henrique CR, Ganz, Patricia A, Garber, Judy, Gauthier-Villars, Marion, Gehrig, Andrea, GEMO Study Collaborators, Gerdes, Anne-Marie, Gesta, Paul, Giannini, Giuseppe, Giraud, Sophie, and Glendon, Gord

Subjects
Internationality, endocrine system diseases, Clinical Sciences, geography, EMBRACE, GEMO Study Collaborators, Databases, breast cancer, Genetic, Clinical Research, Genetics, Humans, 2.1 Biological and endogenous factors, Family, Aetiology, skin and connective tissue diseases, HEBON, Cancer, BRCA2 Protein, Genetics & Heredity, BRCA1 Protein, BRCA1, BRCA2, ovarian cancer, Mutation, ethnicity
Abstract

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

Published
2018

232. The BRCA2 c.68-7T > A variant is not pathogenic:A model for clinical calibration of spliceogenicity

Author

Colombo, Mara, Lòpez-Perolio, Irene, Meeks, Huong D, Caleca, Laura, Parsons, Michael T, Li, Hongyan, De Vecchi, Giovanna, Tudini, Emma, Foglia, Claudia, Mondini, Patrizia, Manoukian, Siranoush, Behar, Raquel, Garcia, Encarna B. Gomez, Meindl, Alfons, Montagna, Marco, Niederacher, Dieter, Schmidt, Ane Y, Varesco, Liliana, Wappenschmidt, Barbara, Bolla, Manjeet K, Dennis, Joe, Michailidou, Kyriaki, Wang, Yi-Qin, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Beckmann, Matthias W, Beeghly-Fadel, Alicia, Benitez, Javier J., Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Chang-Claude, Jenny, Conroy, Don M., Couch, Fergus J, Cox, Angela, Cross, Simon S., Czene, Kamila, Devilee, Peter, Dörk, Thilo, Eriksson, Mikael, Fasching, Peter A, Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Gabrielson, Marike, García-Closas, Montserrat, Giles, Graham G, González-Neira, Anna, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hamann, Ute, Hartman, Mikael, Hauke, Jan, Hollestelle, Antoinette, Hopper, John L, Jakubowska, Anna, Jung, Audrey, Kosma, Veli-Matti, Lambrechts, Diether, Marchand, Loic Le, Lindblom, Annika, Lubinski, Jan, Mannermaa, Arto, Margolin, Sara, Miao, Hui, Milne, Roger L, Neuhausen, Susan L, Nevanlinna, Heli, Olson, Janet E, Peterlongo, Paolo, Peto, Julian, Pylkäs, Katri, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Schneeweiss, Andreas, Schoemaker, Minouk J, See, Mee-Hoong, Southey, Melissa C, Swerdlow, Anthony J., Teo, Soo-Hwang, Toland, Amanda E, Tomlinson, Ian, Truong, Thérèse, van Asperen, Christi J, van den Ouweland, Ans M W, van der Kolk, Lizet, Winqvist, Robert, Yannoukakos, Drakoulis, Zheng, Wei, Dunning, Alison M., Easton, Douglas F., Henderson, R Alex, Hogervorst, Frans, Izatt, Louise, Offitt, Kenneth, Side, Lucy E, van Rensburg, Elizabeth J, Embrace, Study, Hebon, Study, McGuffog, Lesley, Antoniou, Antonis C, Chenevix-Trench, Georgia, Spurdle, Amanda B, Goldgar, David E, de la Hoya, Miguel, and Radice, Paolo

Subjects
Journal Article
Abstract

Although the spliceogenic nature of the BRCA2 c.68-7T > A variant has been demonstrated, its association with cancer risk remains controversial. In this study, we accurately quantified by real-time PCR and digital PCR the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T > A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 × 10-115. There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24), nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the non-pathogenicity of the BRCA2 c.68-7T > A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants. This article is protected by copyright. All rights reserved.

Published
2018

233. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Author

Dadaev, Tokhir, Saunders, Edward J., Newcombe, Paul J., Anokian, Ezequiel, Leongamornlert, Daniel A., Brook, Mark N., Cieza-Borrella, Clara, Mijuskovic, Martina, Wakerell, Sarah, Olama, Ali Amin Al, Schumacher, Fredrick R., Berndt, Sonja I., Benlloch, Sara, Ahmed, Mahbubl, Goh, Chee, Sheng, Xin, Zhang, Zhuo, Muir, Kenneth, Govindasami, Koveela, Lophatananon, Artitaya, Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Tangen, Catherine M., Goodman, Phyllis, Thompson, Ian M., Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail, Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo L.J., Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Hakansson, Niclas, West, Catharine, Dunning, Alison M., Burnet, Neil, Mucci, Lorelei, Giovannucci, Edward, Andriole, Gerald, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Freeman, Laura E.Beane, Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Travis, Ruth C., Key, Tim J., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C., Rosenstein, Barry, Kerns, Sarah, Ostrer, Harry, Lu, Yong Jie, Zhang, Hong Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Fitzgerald, Liesel M., Kibel, Adam S., Drake, Bettina F., Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L., Stampfer, Meir, Park, Jong Y., Sellers, Thomas A., Lin, Hui Yi, Stanford, Janet L., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Ostrander, Elaine A., Geybels, Milan S., Nordestgaard, Børge G., Nielsen, Sune F., Weisher, Maren, Bisbjerg, Rasmus, Røder, Martin Andreas, Iversen, Peter, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Maier, Christiane, Luedeke, Manuel, Schnoeller, Thomas, Kim, Jeri, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Paulo, Paula, Cardoso, Marta, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Razack, Azad, Lim, Jasmine, Teo, Soo Hwang, Lin, Daniel W., Newcomb, Lisa F., Lessel, Davor, Gamulin, Marija, Kulis, Tomislav, Kaneva, Radka, Usmani, Nawaid, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Singhal, Sandeep, Claessens, Frank, Joniau, Steven, Van Den Broeck, Thomas, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Roobol, Monique J., Jenster, Guido, Van Schaik, Ron H.N., Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, Xu, Jianfeng, Khaw, Kay Tee, Cannon-Albright, Lisa, Pandha, Hardev, Michael, Agnieszka, Kierzek, Andrzej, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Lindstrom, Sara, Turman, Constance, Ma, Jing, Hunter, David J., Riboli, Elio, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Hoover, Robert N., Machiela, Mitchell J., Kraft, Peter, Cook, Margaret, Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Spurdle, Amanda, Srinivasan, Srilakshmi, Kedda, Mary Anne, Aitken, Joanne, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Yeadon, Trina, Eckert, Allison, Saunders, Pamela, Haynes, Anne Maree, Papargiris, Melissa, Kujala, Paula, Talala, Kirsi, Murtola, Teemu, Taari, Kimmo, Dearnaley, David, Barnett, Gill, Bentzen, Søren, Elliott, Rebecca, Ranu, Hardeep, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, Davis, Michael, Brown, Paul, George, Anne, Marsden, Gemma, Lane, Athene, Lewis, Sarah J., Berry, Clare, Kulkarni, Girish S., Toi, Ants, Evans, Andrew, Zlotta, Alexandre R., Van Der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Marzec, Jacek, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Zhao, Shan Chao, Ren, Guoping, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Zhang, Yangling, Li, Jie, He, Weiyang, Guo, Jianming, Pedersen, John, Hopper, John L., Milne, Roger, Klim, Aleksandra, Carballo, Ana, Lobato-Busto, Ramón, Peleteiro, Paula, Calvo, Patricia, Aguado, Miguel, Ruiz-Dominguez, José Manuel, Cecchini, Lluís, Mengual, Lourdes, Alcaraz, Antonio, Bustamante, Mariona, Gracia-Lavedan, Esther, Dierssen-Sotos, Trinidad, Gomez-Acebo, Ines, Pow-Sang, Julio, Park, Hyun, Zachariah, Babu, Kluzniak, Wojciech, Kolb, Suzanne, Klarskov, Peter, Stegmaier, Christa, Vogel, Walther, Herkommer, Kathleen, Bohnert, Philipp, Maia, Sofia, Silva, Maria P., De Langhe, Sofie, Thierens, Hubert, Tan, Meng H., Ong, Aik T., Kastelan, Zeljko, Popov, Elenko, Kachakova, Darina, Mitkova, Atanaska, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Bangma, Christopher, Schroder, F. H., Cenee, Sylvie, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Sanchez, Marie, Adolfsson, Jan, Stattin, Par, Johansson, Jan Erik, Cavalli-Bjoerkman, Carin, Karlsson, Ami, Broms, Michael, Wu, Huihai, Tillmans, Lori, Riska, Shaun, Freedman, Matthew, Wiklund, Fredrik, Chanock, Stephen, Henderson, Brian E., Easton, Douglas F., Haiman, Christopher A., Eeles, Rosalind A., Conti, David V., and Kote-Jarai, Zsofia

Abstract

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

Published
2018

234. A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk

Author

Lu, Yingchang Beeghly-Fadiel, Alicia Wu, Lang Guo, Xingyi and Li, Bingshan Schildkraut, Joellen M. Im, Hae Kyung Chen, Yian A. Permuth, Jennifer B. Reid, Brett M. Teer, Jamie K. and Moysich, Kirsten B. Andrulis, Irene L. Anton-Culver, Hoda and Arun, Banu K. Bandera, Elisa V. Barkardottir, Rosa B. and Barnes, Daniel R. Benitez, Javier Bjorge, Line Brenton, James Butzow, Ralf Caldes, Trinidad Caligo, Maria A. and Campbell, Ian Chang-Claude, Jenny Claes, Kathleen B. M. and Couch, Fergus J. Cramer, DanielW. Daly, Mary B. deFazio, Anna Dennis, Joe Diez, Orland Domchek, Susan M. Doerk, Thilo Easton, Douglas F. Eccles, Diana M. Fasching, Peter A. and Fortner, Renee T. Fountzilas, George Friedman, Eitan and Ganz, Patricia A. Garber, Judy Giles, Graham G. Godwin, Andrew K. Goldgar, David E. Goodman, Marc T. Greene, Mark H. and Gronwald, Jacek Hamann, Ute Heitz, Florian Hildebrandt, Michelle A. T. Hogdall, Claus K. Hollestelle, Antoinette and Hulick, Peter J. Huntsman, David G. Imyanitov, Evgeny N. and Isaacs, Claudine Jakubowska, Anna James, Paul Karlan, Beth Y. Kelemen, Linda E. Kiemeney, Lambertus A. Kjaer, Susanne K. Kwong, Ava Le, Nhu D. Leslie, Goska Lesueur, Fabienne and Levine, Douglas A. Mattiello, Amalia May, Taymaa and McGuffog, Lesley McNeish, Iain A. Merritt, Melissa A. and Modugno, Francesmary Montagna, Marco Neuhausen, Susan L. and Nevanlinna, Heli Nielsen, Finn C. Nikitina-Zake, Liene and Nussbaum, Robert L. Offit, Kenneth Olah, Edith Olopade, Olufunmilayo I. Olson, Sara H. Olsson, Hakan Osorio, Ana and Park, Sue K. Parsons, Michael T. Peeters, Petra H. M. and Pejovic, Tanja Peterlongo, Paolo Phelan, Catherine M. and Pujana, Miquel Angel Ramus, Susan J. Rennert, Gad Risch, Harvey Rodriguez, Gustavo C. Rodriguez-Antona, Cristina and Romieu, Isabelle Rookus, Matti A. Rossing, Mary Anne and Rzepecka, Iwona K. Sandler, Dale P. Schmutzler, Rita K. and Setiawan, Veronica W. Sharma, Priyanka Sieh, Weiva Simard, Jacques Singer, Christian F. Song, Honglin Southey, Melissa C. Spurdle, Amanda B. Sutphen, Rebecca Swerdlow, Anthony J. and Teixeira, Manuel R. Teo, Soo H. Thomassen, Mads and Tischkowitz, Marc Toland, Amanda E. Trichopoulou, Antonia and Tung, Nadine Tworoger, Shelley S. van Rensburg, Elizabeth J. and Vanderstichele, Adriaan Vega, Ana Edwards, Digna Velez Webb, Penelope M. Weitzel, Jeffrey N. Wentzensen, Nicolas White, Emily Wolk, Alicja Wu, Anna H. Yannoukakos, Drakoulis and Zorn, Kristin K. Gayther, Simon A. Antoniou, Antonis C. and Berchuck, Andrew Goode, Ellen L. Chenevix-Trench, Georgia and Sellers, Thomas A. Pharoah, Paul D. P. Zheng, Wei Long, Jirong

Subjects
endocrine system diseases, female genital diseases and pregnancy complications
Abstract

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 x 10(-6), we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 x 10(-7), the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 x 10(-3)). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis. Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. (C) 2018 AACR.

Published
2018

235. Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry

Author

Yang, Yaohua, primary, Shu, Xiang, additional, Shu, Xiao-ou, additional, Bolla, Manjeet K., additional, Kweon, Sun-Seog, additional, Cai, Qiuyin, additional, Michailidou, Kyriaki, additional, Wang, Qin, additional, Dennis, Joe, additional, Park, Boyoung, additional, Matsuo, Keitaro, additional, Kwong, Ava, additional, Park, Sue Kyung, additional, Wu, Anna H., additional, Teo, Soo Hwang, additional, Iwasaki, Motoki, additional, Choi, Ji-Yeob, additional, Li, Jingmei, additional, Hartman, Mikael, additional, Shen, Chen-Yang, additional, Muir, Kenneth, additional, Lophatananon, Artitaya, additional, Li, Bingshan, additional, Wen, Wanqing, additional, Gao, Yu-Tang, additional, Xiang, Yong-Bing, additional, Aronson, Kristan J., additional, Spinell, John J., additional, Gago-Dominguez, Manuela, additional, John, Esther M., additional, Kurian, Allison W., additional, Chang-Claude, Jenny, additional, Chen, Shou-Tung, additional, Dörk, Thilo, additional, Evans, D. Gareth R., additional, Schmidt, Marjanka K., additional, Shin, Min-Ho, additional, Giles, Graham G., additional, Milne, Roger L., additional, Simard, Jacques, additional, Kubo, Michiaki, additional, Kraft, Peter, additional, Kang, Daehee, additional, Easton, Douglas F., additional, Zheng, Wei, additional, and Long, Jirong, additional

Published
2019
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236. Identifying 31 novel breast cancer susceptibility loci using data from genome-wide association studies conducted in Asian and European women

Author

Shu, Xiang, primary, Long, Jirong, additional, Cai, Qiuyin, additional, Kweon, Sun-Seog, additional, Choi, Ji-Yeob, additional, Kubo, Michiaki, additional, ParK, Sue K., additional, Bolla, Manjeet K., additional, Dennis, Joe, additional, Wang, Qin, additional, Yang, Yaohua, additional, Shi, Jiajun, additional, Guo, Xingyi, additional, Li, Bingshan, additional, Tao, Ran, additional, Aronson, Kristan J., additional, Chan, Kelvin Y.K., additional, Chan, Tsun L., additional, Gao, Yu-Tang, additional, Hartman, Mikael, additional, Ho, Weang Kee, additional, Ito, Hidemi, additional, Iwasaki, Motoki, additional, Iwata, Hiroji, additional, John, Esther M., additional, Kasuga, Yoshio, additional, Khoo, Ui Soon, additional, Kim, Mi-Kyung, additional, Kurian, Allison W., additional, Kwong, Ava, additional, Li, Jingmei, additional, Lophatananon, Artitaya, additional, Low, Siew-Kee, additional, Mariapun, Shivaani, additional, Matsuda, Koichi, additional, Matsuo, Keitaro, additional, Muir, Kenneth, additional, Noh, Dong-Young, additional, Park, Boyoung, additional, Park, Min-Ho, additional, Shen, Chen-Yang, additional, Shin, Min-Ho, additional, Spinelli, John J., additional, Takahashi, Atsushi, additional, Tseng, Chiuchen, additional, Tsugane, Shoichiro, additional, Wu, Anna H., additional, Xiang, Yong-Bing, additional, Yamaji, Taiki, additional, Zheng, Ying, additional, Milne, Roger L., additional, Dunning, Alison M., additional, Pharoah, Paul D.P., additional, García-Closas, Montserrat, additional, Teo, Soo-Hwang, additional, Shu, Xiao-ou, additional, Kang, Daehee, additional, Easton, Douglas F., additional, Simard, Jacques, additional, and Zheng, Wei, additional

Published
2019
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237. Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Author

Parsons, Michael T., primary, Tudini, Emma, additional, Li, Hongyan, additional, Hahnen, Eric, additional, Wappenschmidt, Barbara, additional, Feliubadaló, Lidia, additional, Aalfs, Cora M., additional, Agata, Simona, additional, Aittomäki, Kristiina, additional, Alducci, Elisa, additional, Alonso‐Cerezo, María Concepción, additional, Arnold, Norbert, additional, Auber, Bernd, additional, Austin, Rachel, additional, Azzollini, Jacopo, additional, Balmaña, Judith, additional, Barbieri, Elena, additional, Bartram, Claus R., additional, Blanco, Ana, additional, Blümcke, Britta, additional, Bonache, Sandra, additional, Bonanni, Bernardo, additional, Borg, Åke, additional, Bortesi, Beatrice, additional, Brunet, Joan, additional, Bruzzone, Carla, additional, Bucksch, Karolin, additional, Cagnoli, Giulia, additional, Caldés, Trinidad, additional, Caliebe, Almuth, additional, Caligo, Maria A., additional, Calvello, Mariarosaria, additional, Capone, Gabriele L., additional, Caputo, Sandrine M., additional, Carnevali, Ileana, additional, Carrasco, Estela, additional, Caux‐Moncoutier, Virginie, additional, Cavalli, Pietro, additional, Cini, Giulia, additional, Clarke, Edward M., additional, Concolino, Paola, additional, Cops, Elisa J., additional, Cortesi, Laura, additional, Couch, Fergus J., additional, Darder, Esther, additional, Hoya, Miguel, additional, Dean, Michael, additional, Debatin, Irmgard, additional, Del Valle, Jesús, additional, Delnatte, Capucine, additional, Derive, Nicolas, additional, Diez, Orland, additional, Ditsch, Nina, additional, Domchek, Susan M., additional, Dutrannoy, Véronique, additional, Eccles, Diana M., additional, Ehrencrona, Hans, additional, Enders, Ute, additional, Evans, D. Gareth, additional, Farra, Chantal, additional, Faust, Ulrike, additional, Felbor, Ute, additional, Feroce, Irene, additional, Fine, Miriam, additional, Foulkes, William D., additional, Galvao, Henrique C.R., additional, Gambino, Gaetana, additional, Gehrig, Andrea, additional, Gensini, Francesca, additional, Gerdes, Anne‐Marie, additional, Germani, Aldo, additional, Giesecke, Jutta, additional, Gismondi, Viviana, additional, Gómez, Carolina, additional, Garcia, Encarna B., additional, González, Sara, additional, Grau, Elia, additional, Grill, Sabine, additional, Gross, Eva, additional, Guerrieri‐Gonzaga, Aliana, additional, Guillaud‐Bataille, Marine, additional, Gutiérrez‐Enríquez, Sara, additional, Haaf, Thomas, additional, Hackmann, Karl, additional, Hansen, Thomas V.O., additional, Harris, Marion, additional, Hauke, Jan, additional, Heinrich, Tilman, additional, Hellebrand, Heide, additional, Herold, Karen N., additional, Honisch, Ellen, additional, Horvath, Judit, additional, Houdayer, Claude, additional, Hübbel, Verena, additional, Iglesias, Silvia, additional, Izquierdo, Angel, additional, James, Paul A., additional, Janssen, Linda A.M., additional, Jeschke, Udo, additional, Kaulfuß, Silke, additional, Keupp, Katharina, additional, Kiechle, Marion, additional, Kölbl, Alexandra, additional, Krieger, Sophie, additional, Kruse, Torben A., additional, Kvist, Anders, additional, Lalloo, Fiona, additional, Larsen, Mirjam, additional, Lattimore, Vanessa L., additional, Lautrup, Charlotte, additional, Ledig, Susanne, additional, Leinert, Elena, additional, Lewis, Alexandra L., additional, Lim, Joanna, additional, Loeffler, Markus, additional, López‐Fernández, Adrià, additional, Lucci‐Cordisco, Emanuela, additional, Maass, Nicolai, additional, Manoukian, Siranoush, additional, Marabelli, Monica, additional, Matricardi, Laura, additional, Meindl, Alfons, additional, Michelli, Rodrigo D., additional, Moghadasi, Setareh, additional, Moles‐Fernández, Alejandro, additional, Montagna, Marco, additional, Montalban, Gemma, additional, Monteiro, Alvaro N., additional, Montes, Eva, additional, Mori, Luigi, additional, Moserle, Lidia, additional, Müller, Clemens R., additional, Mundhenke, Christoph, additional, Naldi, Nadia, additional, Nathanson, Katherine L., additional, Navarro, Matilde, additional, Nevanlinna, Heli, additional, Nichols, Cassandra B., additional, Niederacher, Dieter, additional, Nielsen, Henriette R., additional, Ong, Kai‐ren, additional, Pachter, Nicholas, additional, Palmero, Edenir I., additional, Papi, Laura, additional, Pedersen, Inge Sokilde, additional, Peissel, Bernard, additional, Perez‐Segura, Pedro, additional, Pfeifer, Katharina, additional, Pineda, Marta, additional, Pohl‐Rescigno, Esther, additional, Poplawski, Nicola K., additional, Porfirio, Berardino, additional, Quante, Anne S., additional, Ramser, Juliane, additional, Reis, Rui M., additional, Revillion, Françoise, additional, Rhiem, Kerstin, additional, Riboli, Barbara, additional, Ritter, Julia, additional, Rivera, Daniela, additional, Rofes, Paula, additional, Rump, Andreas, additional, Salinas, Monica, additional, Sánchez de Abajo, Ana María, additional, Schmidt, Gunnar, additional, Schoenwiese, Ulrike, additional, Seggewiß, Jochen, additional, Solanes, Ares, additional, Steinemann, Doris, additional, Stiller, Mathias, additional, Stoppa‐Lyonnet, Dominique, additional, Sullivan, Kelly J., additional, Susman, Rachel, additional, Sutter, Christian, additional, Tavtigian, Sean V., additional, Teo, Soo H., additional, Teulé, Alex, additional, Thomassen, Mads, additional, Tibiletti, Maria Grazia, additional, Tischkowitz, Marc, additional, Tognazzo, Silvia, additional, Toland, Amanda E., additional, Tornero, Eva, additional, Törngren, Therese, additional, Torres‐Esquius, Sara, additional, Toss, Angela, additional, Trainer, Alison H., additional, Tucker, Katherine M., additional, Asperen, Christi J., additional, Mackelenbergh, Marion T., additional, Varesco, Liliana, additional, Vargas‐Parra, Gardenia, additional, Varon, Raymonda, additional, Vega, Ana, additional, Velasco, Ángela, additional, Vesper, Anne‐Sophie, additional, Viel, Alessandra, additional, Vreeswijk, Maaike P. G., additional, Wagner, Sebastian A., additional, Waha, Anke, additional, Walker, Logan C., additional, Walters, Rhiannon J., additional, Wang‐Gohrke, Shan, additional, Weber, Bernhard H. F., additional, Weichert, Wilko, additional, Wieland, Kerstin, additional, Wiesmüller, Lisa, additional, Witzel, Isabell, additional, Wöckel, Achim, additional, Woodward, Emma R., additional, Zachariae, Silke, additional, Zampiga, Valentina, additional, Zeder‐Göß, Christine, additional, Investigators, KConFab, additional, Lázaro, Conxi, additional, Nicolo, Arcangela, additional, Radice, Paolo, additional, Engel, Christoph, additional, Schmutzler, Rita K., additional, Goldgar, David E., additional, and Spurdle, Amanda B., additional

Published
2019
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238. Evaluation of Cancer-Based Criteria for Use in MainstreamBRCA1andBRCA2Genetic Testing in Patients With Breast Cancer

Author

Kemp, Zoe, primary, Turnbull, Alice, additional, Yost, Shawn, additional, Seal, Sheila, additional, Mahamdallie, Shazia, additional, Poyastro-Pearson, Emma, additional, Warren-Perry, Margaret, additional, Eccleston, Anthony, additional, Tan, Min-Min, additional, Teo, Soo Hwang, additional, Turner, Nicholas, additional, Strydom, Ann, additional, George, Angela, additional, and Rahman, Nazneen, additional

Published
2019
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239. An Oncogenic Role for Four-Jointed Box 1 (FJX1) in Nasopharyngeal Carcinoma

Author

Chai, San Jiun, primary, Ahmad Zabidi, Muhammad Mamduh, additional, Gan, Siew Pey, additional, Rajadurai, Pathmanathan, additional, Lim, Paul Vey Hong, additional, Ng, Ching Ching, additional, Yap, Lee Fah, additional, Teo, Soo Hwang, additional, Lim, Kue Peng, additional, Patel, Vyomesh, additional, and Cheong, Sok Ching, additional

Published
2019
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240. The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium

Author

Ugai, Tomotaka, primary, Milne, Roger L., additional, Ito, Hidemi, additional, Aronson, Kristan J., additional, Bolla, Manjeet K., additional, Chan, Tsun, additional, Chan, Ching W., additional, Choi, Ji‐Yeob, additional, Conroy, Don M., additional, Dennis, Joe, additional, Dunning, Alison M., additional, Easton, Douglas F., additional, Gaborieau, Valerie, additional, Gonzalez‐Neira, Anna, additional, Hartman, Mikael, additional, Healey, Catherine S., additional, Iwasaki, Motoki, additional, John, Esther M., additional, Kang, Daehee, additional, Kim, Sung‐Won, additional, Kwong, Ava, additional, Lophatananon, Artitaya, additional, Michailidou, Kyriaki, additional, Taib, Nur Aishah Mohd, additional, Muir, Kenneth, additional, Park, Sue K., additional, Pharoah, Paul D. P., additional, Sangrajrang, Suleeporn, additional, Shen, Chen‐Yang, additional, Shu, Xiao‐Ou, additional, Spinelli, John J., additional, Teo, Soo H., additional, Tessier, Daniel C., additional, Tseng, Chiu‐Chen, additional, Tsugane, Shoichiro, additional, Vincent, Daniel, additional, Wang, Qin, additional, Wu, Anna H., additional, Wu, Pei‐Ei, additional, Zheng, Wei, additional, and Matsuo, Keitaro, additional

Published
2019
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241. Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women

Author

Lawrenson, Kate, primary, Song, Fengju, additional, Hazelett, Dennis J., additional, Kar, Siddhartha P., additional, Tyrer, Jonathan, additional, Phelan, Catherine M., additional, Corona, Rosario I., additional, Rodríguez-Malavé, Norma I., additional, Seo, Ji-Hei, additional, Adler, Emily, additional, Coetzee, Simon G., additional, Segato, Felipe, additional, Fonseca, Marcos A.S., additional, Amos, Christopher I., additional, Carney, Michael E., additional, Chenevix-Trench, Georgia, additional, Choi, Jiyeob, additional, Doherty, Jennifer A., additional, Jia, Weihua, additional, Jin, Gang J., additional, Kim, Byoung-Gie, additional, Le, Nhu D., additional, Lee, Juyeon, additional, Li, Lian, additional, Lim, Boon K., additional, Adenan, Noor A., additional, Mizuno, Mika, additional, Park, Boyoung, additional, Pearce, Celeste L., additional, Shan, Kang, additional, Shi, Yongyong, additional, Shu, Xiao-Ou, additional, Sieh, Weiva, additional, Thompson, Pamela J., additional, Wilkens, Lynne R., additional, Wei, Qingyi, additional, Woo, Yin L., additional, Yan, Li, additional, Karlan, Beth Y., additional, Freedman, Matthew L., additional, Noushmehr, Houtan, additional, Goode, Ellen L., additional, Berchuck, Andrew, additional, Sellers, Thomas A., additional, Teo, Soo-Hwang, additional, Zheng, Wei, additional, Matsuo, Keitaro, additional, Park, Sue, additional, Chen, Kexin, additional, Pharoah, Paul D.P., additional, Gayther, Simon A., additional, and Goodman, Marc T., additional

Published
2019
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242. Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk

Author

Yang, Yaohua, primary, Wu, Lang, additional, Shu, Xiang, additional, Lu, Yingchang, additional, Shu, Xiao-Ou, additional, Cai, Qiuyin, additional, Beeghly-Fadiel, Alicia, additional, Li, Bingshan, additional, Ye, Fei, additional, Berchuck, Andrew, additional, Anton-Culver, Hoda, additional, Banerjee, Susana, additional, Benitez, Javier, additional, Bjørge, Line, additional, Brenton, James D., additional, Butzow, Ralf, additional, Campbell, Ian G., additional, Chang-Claude, Jenny, additional, Chen, Kexin, additional, Cook, Linda S., additional, Cramer, Daniel W., additional, deFazio, Anna, additional, Dennis, Joe, additional, Doherty, Jennifer A., additional, Dörk, Thilo, additional, Eccles, Diana M., additional, Edwards, Digna Velez, additional, Fasching, Peter A., additional, Fortner, Renée T., additional, Gayther, Simon A., additional, Giles, Graham G., additional, Glasspool, Rosalind M., additional, Goode, Ellen L., additional, Goodman, Marc T., additional, Gronwald, Jacek, additional, Harris, Holly R., additional, Heitz, Florian, additional, Hildebrandt, Michelle A., additional, Høgdall, Estrid, additional, Høgdall, Claus K., additional, Huntsman, David G., additional, Kar, Siddhartha P., additional, Karlan, Beth Y., additional, Kelemen, Linda E., additional, Kiemeney, Lambertus A., additional, Kjaer, Susanne K., additional, Koushik, Anita, additional, Lambrechts, Diether, additional, Le, Nhu D., additional, Levine, Douglas A., additional, Massuger, Leon F., additional, Matsuo, Keitaro, additional, May, Taymaa, additional, McNeish, Iain A., additional, Menon, Usha, additional, Modugno, Francesmary, additional, Monteiro, Alvaro N., additional, Moorman, Patricia G., additional, Moysich, Kirsten B., additional, Ness, Roberta B., additional, Nevanlinna, Heli, additional, Olsson, Håkan, additional, Onland-Moret, N. Charlotte, additional, Park, Sue K., additional, Paul, James, additional, Pearce, Celeste L., additional, Pejovic, Tanja, additional, Phelan, Catherine M., additional, Pike, Malcolm C., additional, Ramus, Susan J., additional, Riboli, Elio, additional, Rodriguez-Antona, Cristina, additional, Romieu, Isabelle, additional, Sandler, Dale P., additional, Schildkraut, Joellen M., additional, Setiawan, Veronica W., additional, Shan, Kang, additional, Siddiqui, Nadeem, additional, Sieh, Weiva, additional, Stampfer, Meir J., additional, Sutphen, Rebecca, additional, Swerdlow, Anthony J., additional, Szafron, Lukasz M., additional, Teo, Soo Hwang, additional, Tworoger, Shelley S., additional, Tyrer, Jonathan P., additional, Webb, Penelope M., additional, Wentzensen, Nicolas, additional, White, Emily, additional, Willett, Walter C., additional, Wolk, Alicja, additional, Woo, Yin Ling, additional, Wu, Anna H., additional, Yan, Li, additional, Yannoukakos, Drakoulis, additional, Chenevix-Trench, Georgia, additional, Sellers, Thomas A., additional, Pharoah, Paul D.P., additional, Zheng, Wei, additional, and Long, Jirong, additional

Published
2019
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244. Patient-reported outcome measures among breast cancer survivors: A cross-sectional comparison between Malaysia and high-income countries.

Author

Rajaram, Nadia, Lim, Zhi Ying, Song, Chin Vern, Kaur, Ranjit, Mohd Taib, Nur Aishah, Muhamad, Mazanah, Ong, Wee Loon, Schouwenburg, Maartje, See, Mee Hoong, Teo, Soo‐Hwang, Saunders, Christobel, Yip, Cheng Har, and Teo, Soo-Hwang

Abstract

Objectives: Patient-reported outcomes (PROs) in high-income countries (HICs) suggest that physical, emotional, and psychological needs are important in cancer care. To date, there have been few inconsistent descriptions of PROs in low-income and middle-income Asian countries. Using a standard questionnaire developed by the International Consortium for Health Outcomes Measurement (ICHOM), we compared the perceived importance of PROs between patients in Malaysia and those in HICs and between clusters of Malaysian women.Methods: Breast cancer patients were recruited from three Malaysian hospitals between June and November 2017. We compared the proportion of patients who rated PROs as very important (scored 7-9 on a 9-point Likert scale) between Malaysian patients and data collected from patients in HICs via the ICHOM questionnaire development process, using logistic regression. A two-step cluster analysis explored differences in PROs among Malaysian patients.Results: The most important PROs for both cohorts were survival, overall well-being, and physical functioning. Compared with HIC patients (n = 1177), Malaysian patients (n = 969) were less likely to rate emotional (78% vs 90%), cognitive (76% vs 84%), social (72% vs 81%), and sexual (30% vs 56%) functioning as very important outcomes (P < 0.001). Cluster analysis suggests that older, parous, Malaysian women, who were less likely to have received breast reconstructive surgery, were more likely to rate body image and satisfaction with the breast as very important outcomes.Conclusion: Taking into account the differences in PROs by cultural and socioeconomic settings could improve patient expectation of services and refine the assessment of cancer care outcomes. [ABSTRACT FROM AUTHOR]

Published
2019
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245. Characterisation of protein-truncating and missense variants in PALB2in 15 768 women from Malaysia and Singapore

Author

Ng, Pei Sze, Boonen, Rick ACM, Wijaya, Eldarina, Chong, Chan Eng, Sharma, Milan, Knaup, Sabine, Mariapun, Shivaani, Ho, Weang Kee, Lim, Joanna, Yoon, Sook-Yee, Mohd Taib, Nur Aishah, See, Mee Hoong, Li, Jingmei, Lim, Swee Ho, Tan, Ern Yu, Tan, Benita Kiat-Tee, Tan, Su-Ming, Tan, Veronique Kiat-Mien, van Dam, Rob Martinus, Rahmat, Kartini, Yip, Cheng Har, Carvalho, Sara, Luccarini, Craig, Baynes, Caroline, Dunning, Alison M, Antoniou, Antonis, van Attikum, Haico, Easton, Douglas F, Hartman, Mikael, and Teo, Soo Hwang

Abstract

BackgroundRare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population.MethodsMutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays.ResultsPTVs in PALB2were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks.ConclusionDespite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

Published
2022
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246. Oncologist-led BRCAcounselling improves access to cancer genetic testing in middle-income Asian country, with no significant impact on psychosocial outcomes

Author

Yoon, Sook-Yee, Wong, Siu Wan, Lim, Joanna, Ahmad, Syuhada, Mariapun, Shivaani, Padmanabhan, Heamanthaa, Hassan, Nur Tiara, Lau, Shao Yan, Ch'ng, Gaik-Siew, Haniffa, Muzhirah, Ong, Winnie P, Rethanavelu, Kavitha, Moey, Lip Hen, Keng, Wee Teik, Omar, Jamil, Mohd Abas, Mohd Norazam, Yong, Chee Meng, Ramasamy, Vickneswaren, Md Noor, Mohd Rushdan, Aliyas, Ismail, Lim, Michael C K, Suberamaniam, Anuradha, Mat Adenan, Noor Azmi, Ahmad, Zatul Akmar, Ho, Gwo Fuang, Abdul Malik, Rozita, Subramaniam, Suguna, Khoo, Boom Ping, Raja, Arivendran, Chin, Yeung Sing, Sim, Wee Wee, Teh, Beng Hock, Kho, Swee Kiong, Ong, Eunice S E, Voon, Pei Jye, Ismail, Ghazali, Lee, Chui Ling, Abdullah, Badrul Zaman, Loo, Kwong Sheng, Lim, Chun Sen, Lee, Saw Joo, Lim, Keng Joo Lim, Shafiee, Mohamad Nasir, Ismail, Fuad, Latiff, Zarina Abdul, Ismail, Mohd Pazudin, Mohamed Jamli, Mohamad Faiz, Kumarasamy, Suresh, Leong, Kin Wah, Low, John, Md Yusof, Mastura, Ahmad Mustafa, Ahmad Muzamir, Mat Ali, Nor Huda, Makanjang, Mary, Tayib, Shahila, Cheah, Nellie, Lim, Boon Kiong, Fong, Chee Kin, Foo, Yoke Ching, Mellor Abdullah, Matin, Tan, Teck Sin, Chow, Doris S Y, Ho, Kean Fatt, Raman, Rakesh, Radzi, Ahmad, Deniel, Azura, Teoh, Daren C Y, Ang, Soo Fan, Joseph, Joseph K, Ng, Paul Hock Oon, Tho, Lye-Mun, Ahmad, Azura Rozila, Muin, Ileena, Bleiker, Eveline, George, Angela, Thong, Meow-Keong, Woo, Yin Ling, and Teo, Soo Hwang

Abstract

BackgroundIdentifying patients with BRCAmutations is clinically important to inform on the potential response to treatment and for risk management of patients and their relatives. However, traditional referral routes may not meet clinical needs, and therefore, mainstreaming cancer genetics has been shown to be effective in some high-income and high health-literacy settings. To date, no study has reported on the feasibility of mainstreaming in low-income and middle-income settings, where the service considerations and health literacy could detrimentally affect the feasibility of mainstreaming.MethodsThe Mainstreaming Genetic Counselling for Ovarian Cancer Patients (MaGiC) study is a prospective, two-arm observational study comparing oncologist-led and genetics-led counselling. This study included 790 multiethnic patients with ovarian cancer from 23 sites in Malaysia. We compared the impact of different method of delivery of genetic counselling on the uptake of genetic testing and assessed the feasibility, knowledge and satisfaction of patients with ovarian cancer.ResultsOncologists were satisfied with the mainstreaming experience, with 95% indicating a desire to incorporate testing into their clinical practice. The uptake of genetic testing was similar in the mainstreaming and genetics arm (80% and 79%, respectively). Patient satisfaction was high, whereas decision conflict and psychological impact were low in both arms of the study. Notably, decisional conflict, although lower than threshold, was higher for the mainstreaming group compared with the genetics arm. Overall, 13.5% of patients had a pathogenic variant in BRCA1or BRCA2,and there was no difference between psychosocial measures for carriers in both arms.ConclusionThe MaGiC study demonstrates that mainstreaming cancer genetics is feasible in low-resource and middle-resource Asian setting and increased coverage for genetic testing.

Published
2022
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249. Feasibility of Patient Navigation to Improve Breast Cancer Care in Malaysia

Author

Yeoh, Zi-Yi, primary, Jaganathan, Maheswari, additional, Rajaram, Nadia, additional, Rawat, Sudha, additional, Tajudeen, Nurul Ain, additional, Rahim, Norlia, additional, Zainal, Nur Hidayati, additional, Maniam, Sakthi, additional, Suvelayutnan, Ushananthiny, additional, Yaacob, Rahani, additional, Krishnapillai, Vijayalakshmi, additional, Kamal, Meor Zamari Meor, additional, Teo, Soo-Hwang, additional, and Wahab, Mohamed Yusof Abdul, additional

Published
2018
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