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40 results on '"Tripathi, Vishakha"'

1. “I’m quite proud of how we’ve handled it”: health professionals’ experiences of returning additional findings from the 100,000 genomes project

Author

Stafford-Smith, Bethany, Gurasashvili, Jana, Peter, Michelle, Daniel, Morgan, Balasubramanian, Meena, Bownass, Lucy, Brennan, Paul, Cleaver, Ruth, Clowes, Virginia, Costello, Philandra, DeSouza, Bianca, Dubois, Louise, Harrison, Rachel, Hawkes, Lara, Jones, Elizabeth A., Kraus, Alison, McEntagart, Meriel, Somarathi, Suresh, Taylor, Amy, Tripathi, Vishakha, Chitty, Lyn S., and Hill, Melissa

Published
2024
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2. Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium

Author

Kast, Karin, John, Esther M., Hopper, John L., Andrieu, Nadine, Noguès, Catherine, Mouret-Fourme, Emmanuelle, Lasset, Christine, Fricker, Jean-Pierre, Berthet, Pascaline, Mari, Véronique, Salle, Lucie, Schmidt, Marjanka K., Ausems, Margreet G. E. M., Garcia, Encarnacion B. Gomez, van de Beek, Irma, Wevers, Marijke R., Evans, D. Gareth, Tischkowitz, Marc, Lalloo, Fiona, Cook, Jackie, Izatt, Louise, Tripathi, Vishakha, Snape, Katie, Musgrave, Hannah, Sharif, Saba, Murray, Jennie, Colonna, Sarah V., Andrulis, Irene L., Daly, Mary B., Southey, Melissa C., de la Hoya, Miguel, Osorio, Ana, Foretova, Lenka, Berkova, Dita, Gerdes, Anne-Marie, Olah, Edith, Jakubowska, Anna, Singer, Christian F., Tan, Yen, Augustinsson, Annelie, Rantala, Johanna, Simard, Jacques, Schmutzler, Rita K., Milne, Roger L., Phillips, Kelly-Anne, Terry, Mary Beth, Goldgar, David, van Leeuwen, Flora E., Mooij, Thea M., Antoniou, Antonis C., Easton, Douglas F., Rookus, Matti A., and Engel, Christoph

Published
2023
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3. PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants

Author

Muranen, Taru A., Morra, Anna, Khan, Sofia, Barnes, Daniel R., Bolla, Manjeet K., Dennis, Joe, Keeman, Renske, Leslie, Goska, Parsons, Michael T., Wang, Qin, Ahearn, Thomas U., Aittomäki, Kristiina, Andrulis, Irene L., Arun, Banu K., Behrens, Sabine, Bialkowska, Katarzyna, Bojesen, Stig E., Camp, Nicola J., Chang-Claude, Jenny, Czene, Kamila, Devilee, Peter, Domchek, Susan M., Dunning, Alison M., Engel, Christoph, Evans, D. Gareth, Gago-Dominguez, Manuela, García-Closas, Montserrat, Gerdes, Anne-Marie, Glendon, Gord, Guénel, Pascal, Hahnen, Eric, Hamann, Ute, Hanson, Helen, Hooning, Maartje J., Hoppe, Reiner, Izatt, Louise, Jakubowska, Anna, James, Paul A., Kristensen, Vessela N., Lalloo, Fiona, Lindeman, Geoffrey J., Mannermaa, Arto, Margolin, Sara, Neuhausen, Susan L., Newman, William G., Peterlongo, Paolo, Phillips, Kelly-Anne, Pujana, Miquel Angel, Rantala, Johanna, Rønlund, Karina, Saloustros, Emmanouil, Schmutzler, Rita K., Schneeweiss, Andreas, Singer, Christian F., Suvanto, Maija, Tan, Yen Yen, Teixeira, Manuel R., Thomassen, Mads, Tischkowitz, Marc, Tripathi, Vishakha, Wappenschmidt, Barbara, Zhao, Emily, Easton, Douglas F., Antoniou, Antonis C., Chenevix-Trench, Georgia, Pharoah, Paul D. P., Schmidt, Marjanka K., Blomqvist, Carl, and Nevanlinna, Heli

Published
2023
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4. The genetic counsellor role in the United Kingdom: Position on behalf of the Association of Genetic Nurses and Counsellors (AGNC), Endorsed by the Genetic Counsellor Registration Board (GCRB) and Academy for Healthcare Science (AHCS)

Author

Middleton, Anna, Taverner, Nicola, Moreton, Natalie, Rizzo, Roberta, Houghton, Catherine, Watt, Catherine, Horton, Esther, Levene, Sara, Leonard, Phil, Melville, Athalie, Ellis, Somya, Tripathi, Vishakha, Patch, Christine, and Jenkins, Elaine

Published
2023
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6. Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

Author

Hakkaart, Christopher, Pearson, John F., Marquart, Louise, Dennis, Joe, Wiggins, George A. R., Barnes, Daniel R., Robinson, Bridget A., Mace, Peter D., Aittomäki, Kristiina, Andrulis, Irene L., Arun, Banu K., Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B., Belhadj, Sami, Berger, Lieke, Blok, Marinus J., Boonen, Susanne E., Borde, Julika, Bradbury, Angela R., Brunet, Joan, Buys, Saundra S., Caligo, Maria A., Campbell, Ian, Chung, Wendy K., Claes, Kathleen B. M., Collonge-Rame, Marie-Agnès, Cook, Jackie, Cosgrove, Casey, Couch, Fergus J., Daly, Mary B., Dandiker, Sita, Davidson, Rosemarie, de la Hoya, Miguel, de Putter, Robin, Delnatte, Capucine, Dhawan, Mallika, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Donaldson, Alan, Eason, Jacqueline, Easton, Douglas F., Ehrencrona, Hans, Engel, Christoph, Evans, D. Gareth, Faust, Ulrike, Feliubadaló, Lidia, Fostira, Florentia, Friedman, Eitan, Frone, Megan, Frost, Debra, Garber, Judy, Gayther, Simon A., Gehrig, Andrea, Gesta, Paul, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Hahnen, Eric, Hake, Christopher R., Hamann, Ute, Hansen, Thomas V. O., Hauke, Jan, Hentschel, Julia, Herold, Natalie, Honisch, Ellen, Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Izquierdo, Angel, Jakubowska, Anna, James, Paul A., Janavicius, Ramunas, John, Esther M., Joseph, Vijai, Karlan, Beth Y., Kemp, Zoe, Kirk, Judy, Konstantopoulou, Irene, Koudijs, Marco, Kwong, Ava, Laitman, Yael, Lalloo, Fiona, Lasset, Christine, Lautrup, Charlotte, Lazaro, Conxi, Legrand, Clémentine, Leslie, Goska, Lesueur, Fabienne, Mai, Phuong L., Manoukian, Siranoush, Mari, Véronique, Martens, John W. M., McGuffog, Lesley, Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Montagna, Marco, Moserle, Lidia, Mouret-Fourme, Emmanuelle, Musgrave, Hannah, Nambot, Sophie, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Yie, Joanne Ngeow Yuen, Nguyen-Dumont, Tu, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Osorio, Ana, Ott, Claus-Eric, Park, Sue K., Parsons, Michael T., Pedersen, Inge Sokilde, Peixoto, Ana, Perez-Segura, Pedro, Peterlongo, Paolo, Pocza, Timea, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Rodriguez, Gustavo C., Rønlund, Karina, Rosenberg, Efraim H., Rossing, Maria, Schmutzler, Rita K., Shah, Payal D., Sharif, Saba, Sharma, Priyanka, Side, Lucy E., Simard, Jacques, Singer, Christian F., Snape, Katie, Steinemann, Doris, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teo, Soo Hwang, Thomassen, Mads, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Trainer, Alison H., Tripathi, Vishakha, Tung, Nadine, van Engelen, Klaartje, van Rensburg, Elizabeth J., Vega, Ana, Viel, Alessandra, Walker, Lisa, Weitzel, Jeffrey N., Wevers, Marike R., Chenevix-Trench, Georgia, Spurdle, Amanda B., Antoniou, Antonis C., and Walker, Logan C.

Published
2022
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7. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

Author

Adams, Lisa, Adlard, Julian, Alfonso, Rosa, Ali, Saira, Andrew, Angela, Araújo, Luís, Azam, Nazya, Ball, Darran, Barker, Queenstone, Basevitch, Alon, Benton, Barbara, Berlin, Cheryl, Bermingham, Nicola, Biller, Leah, Bloss, Angela, Bradford, Matilda, Bradshaw, Nicola, Branson, Amy, Brendler, Charles, Brennan, Maria, Bulman, Barbara, Burgess, Lucy, Cahill, Declan, Callard, Alice, Calvo Verges, Nuria, Cardoso, Marta, Carter, Vanda, Catanzaro, Mario, Chamberlain, Anthony, Chapman, Cyril, Chong, Michael, Clark, Caroline, Clowes, Virginia, Cogley, Lyn, Cole, Trevor, Compton, Cecilia, Conner, Tom, Cookson, Sandra, Cornford, Philip, Costello, Philandra, Coulier, Laura, Davies, Michaela, Dechet, Christopher, DeSouza, Bianca, Devlin, Gemma, Douglas, Fiona, Douglas, Emma, Dudakia, Darshna, Duncan, Alexis, Ellery, Natalie, Everest, Sarah, Freemantle, Sue, Frydenberg, Mark, Fuller, Debbie, Gabriel, Camila, Gale, Madeline, Garcia, Lynda, Gay, Simona, Genova, Elena, George, Angela, Georgiou, Demetra, Gisbert, Alexandra, Gleeson, Margaret, Glover, Wayne, Gnanapragasam, Vincent, Goff, Sally, Goldgar, David, Gonçalves, Nuno, Goodman, Selina, Gorrie, Jennifer, Gott, Hannah, Grant, Anna, Gray, Catherine, Griffiths, Julie, Gupwell, Karin, Gurasashvili, Jana, Hanslien, Eldbjørg, Haraldsdottir, Sigurdis, Hart, Rachel, Hartigan, Catherine, Hawkes, Lara, Heaton, Tricia, Henderson, Alex, Henrique, Rui, Hilario, Kathrine, Hill, Kathryn, Hulick, Peter, Hunt, Clare, Hutchings, Melanie, Ibitoye, Rita, Inglehearn, Thomas, Ireland, Joanna, Islam, Farah, Ismail, Siti, Jacobs, Chris, James, Denzil, Jenkins, Sharon, Jobson, Irene, Johnstone, Anne, Jones, Oliver, Josefsberg Ben-Yehoshua, Sagi, Kaemba, Beckie, Kaul, Karen, Kemp, Zoe, Kinsella, Netty, Klehm, Margaret, Kockelbergh, Roger, Kohut, Kelly, Kosicka-Slawinska, Monika, Kulkarni, Anjana, Kumar, Pardeep, Lam, Jimmy, LeButt, Mandy, Leibovici, Dan, Lim, Ramona, Limb, Lauren, Lomas, Claire, Longmuir, Mark, López, Consol, Magnani, Tiziana, Maia, Sofia, Maiden, Jessica, Male, Alison, Manalo, Merrie, Martin, Phoebe, McBride, Donna, McGuire, Michael, McMahon, Romayne, McNally, Claire, McVeigh, Terri, Melzer, Ehud, Mencias, Mark, Mercer, Catherine, Mitchell, Gillian, Mora, Josefina, Morton, Catherine, Moss, Cathryn, Murphy, Morgan, Murphy, Declan, Mzazi, Shumi, Nadolski, Maria, Newlin, Anna, Nogueira, Pedro, O'Keefe, Rachael, O'Toole, Karen, O'Connell, Shona, Ogden, Chris, Okoth, Linda, Oliveira, Jorge, Paez, Edgar, Palou, Joan, Park, Linda, Patel, Nafisa, Paulo Souto, João, Pearce, Allison, Peixoto, Ana, Perez, Kimberley, Petelin, Lara, Pichert, Gabriella, Poile, Charlotte, Potter, Alison, Preitner, Nadia, Purnell, Helen, Quinn, Ellen, Radice, Paolo, Rankin, Brigette, Rees, Katie, Renton, Caroline, Richardson, Kate, Risby, Peter, Rogers, Jason, Ruderman, Maggie, Ruiz, April, Sajoo, Anaar, Salvatore, Natale, Sands, Victoria, Sanguedolce, Francesco, Sattar, Ayisha, Saunders, Kathryn, Schofield, Lyn, Scott, Rodney, Searle, Anne, Sehra, Ravinder, Selkirk, Christina, Shackleton, Kylie, Shanley, Sue, Shaw, Adam, Shevrin, Daniel, Shipman, Hannah, Sidat, Zahirah, Siguake, Kas, Simon, Kate, Smyth, Courtney, Snadden, Lesley, Solanky, Nita, Solomons, Joyce, Sorrentino, Margherita, Stayner, Barbara, Stephenson, Robert, Stoffel, Elena, Thomas, Maggie, Thompson, Alan, Tidey, Lizzie, Tischkowitz, Marc, Torokwa, Audrey, Townshend, Sharron, Treherne, Katy, Tricker, Karen, Trinh, Quoc-Dien, Tripathi, Vishakha, Turnbull, Clare, Valdagni, Riccardo, Van As, Nicholas, Venne, Vickie, Verdon, Lizzie, Vitellaro, Marco, Vogel, Kristen, Walker, Lisa, Watford, Amy, Watt, Cathy, Weintroub, Ilana, Weiss, Shelly, Weissman, Scott, Weston, Michelle, Wiggins, Jennifer, Wise, Gillian, Woodhouse, Christopher, Yesildag, Pembe, Youngs, Alice, Yurgelun, Matthew, Zollo, Fabiana, Bancroft, Elizabeth K, Page, Elizabeth C, Brook, Mark N, Thomas, Sarah, Taylor, Natalie, Pope, Jennifer, McHugh, Jana, Jones, Ann-Britt, Karlsson, Questa, Merson, Susan, Ong, Kai Ren, Hoffman, Jonathan, Huber, Camilla, Maehle, Lovise, Grindedal, Eli Marie, Stormorken, Astrid, Evans, D Gareth, Rothwell, Jeanette, Lalloo, Fiona, Brady, Angela F, Bartlett, Marion, Snape, Katie, Hanson, Helen, James, Paul, McKinley, Joanne, Mascarenhas, Lyon, Syngal, Sapna, Ukaegbu, Chinedu, Side, Lucy, Thomas, Tessy, Barwell, Julian, Teixeira, Manuel R, Izatt, Louise, Suri, Mohnish, Macrae, Finlay A, Poplawski, Nicola, Chen-Shtoyerman, Rakefet, Ahmed, Munaza, Musgrave, Hannah, Nicolai, Nicola, Greenhalgh, Lynn, Brewer, Carole, Pachter, Nicholas, Spigelman, Allan D, Azzabi, Ashraf, Helfand, Brian T, Halliday, Dorothy, Buys, Saundra, Ramon y Cajal, Teresa, Donaldson, Alan, Cooney, Kathleen A, Harris, Marion, McGrath, John, Davidson, Rosemarie, Taylor, Amy, Cooke, Peter, Myhill, Kathryn, Hogben, Matthew, Aaronson, Neil K, Ardern-Jones, Audrey, Bangma, Chris H, Castro, Elena, Dearnaley, David, Dias, Alexander, Dudderidge, Tim, Eccles, Diana M, Green, Kate, Eyfjord, Jorunn, Falconer, Alison, Foster, Christopher S, Gronberg, Henrik, Hamdy, Freddie C, Johannsson, Oskar, Khoo, Vincent, Lilja, Hans, Lindeman, Geoffrey J, Lubinski, Jan, Axcrona, Karol, Mikropoulos, Christos, Mitra, Anita V, Moynihan, Clare, Ni Raghallaigh, Holly, Rennert, Gad, Collier, Rebecca, Offman, Judith, Kote-Jarai, Zsofia, and Eeles, Rosalind A

Published
2021
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8. Validation of the BOADICEA model in a prospective cohort of BRCA1/2 pathogenic variant carriers.

Author

Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Genetica Klinische Genetica, Yang, Xin, Mooij, Thea M, Leslie, Goska, Ficorella, Lorenzo, Andrieu, Nadine, Kast, Karin, Singer, Christian F, Jakubowska, Anna, van Gils, Carla H, Tan, Yen Y, Engel, Christoph, Adank, Muriel A, van Asperen, Christi J, Ausems, Margreet G E M, Berthet, Pascaline, Collee, Margriet J, Cook, Jackie A, Eason, Jacqueline, Spaendonck-Zwarts, Karin Y van, Evans, D Gareth, Gómez García, Encarna B, Hanson, Helen, Izatt, Louise, Kemp, Zoe, Lalloo, Fiona, Lasset, Christine, Lesueur, Fabienne, Musgrave, Hannah, Nambot, Sophie, Noguès, Catherine, Oosterwijk, Jan C, Stoppa-Lyonnet, Dominique, Tischkowitz, Marc, Tripathi, Vishakha, Wevers, Marijke R, Zhao, Emily, van Leeuwen, Flora E, Schmidt, Marjanka K, Easton, Douglas F, Rookus, Matti A, Antoniou, Antonis C, EMBRACE Collaborators, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Genetica Klinische Genetica, Yang, Xin, Mooij, Thea M, Leslie, Goska, Ficorella, Lorenzo, Andrieu, Nadine, Kast, Karin, Singer, Christian F, Jakubowska, Anna, van Gils, Carla H, Tan, Yen Y, Engel, Christoph, Adank, Muriel A, van Asperen, Christi J, Ausems, Margreet G E M, Berthet, Pascaline, Collee, Margriet J, Cook, Jackie A, Eason, Jacqueline, Spaendonck-Zwarts, Karin Y van, Evans, D Gareth, Gómez García, Encarna B, Hanson, Helen, Izatt, Louise, Kemp, Zoe, Lalloo, Fiona, Lasset, Christine, Lesueur, Fabienne, Musgrave, Hannah, Nambot, Sophie, Noguès, Catherine, Oosterwijk, Jan C, Stoppa-Lyonnet, Dominique, Tischkowitz, Marc, Tripathi, Vishakha, Wevers, Marijke R, Zhao, Emily, van Leeuwen, Flora E, Schmidt, Marjanka K, Easton, Douglas F, Rookus, Matti A, Antoniou, Antonis C, and EMBRACE Collaborators

Published
2024

9. Additional file 3 of Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium

Author

Kast, Karin, John, Esther M., Hopper, John L., Andrieu, Nadine, Noguès, Catherine, Mouret-Fourme, Emmanuelle, Lasset, Christine, Fricker, Jean-Pierre, Berthet, Pascaline, Mari, Véronique, Salle, Lucie, Schmidt, Marjanka K., Ausems, Margreet G. E. M., Garcia, Encarnacion B. Gomez, van de Beek, Irma, Wevers, Marijke R., Evans, D. Gareth, Tischkowitz, Marc, Lalloo, Fiona, Cook, Jackie, Izatt, Louise, Tripathi, Vishakha, Snape, Katie, Musgrave, Hannah, Sharif, Saba, Murray, Jennie, Colonna, Sarah V., Andrulis, Irene L., Daly, Mary B., Southey, Melissa C., de la Hoya, Miguel, Osorio, Ana, Foretova, Lenka, Berkova, Dita, Gerdes, Anne-Marie, Olah, Edith, Jakubowska, Anna, Singer, Christian F., Tan, Yen, Augustinsson, Annelie, Rantala, Johanna, Simard, Jacques, Schmutzler, Rita K., Milne, Roger L., Phillips, Kelly-Anne, Terry, Mary Beth, Goldgar, David, van Leeuwen, Flora E., Mooij, Thea M., Antoniou, Antonis C., Easton, Douglas F., Rookus, Matti A., and Engel, Christoph

Abstract

Additional file 3: Table S3. Retrospective analysis of height, body mass index, weight change and breast cancer risk, by menopausal status.

Published
2023
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10. Additional file 1 of Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium

Author

Kast, Karin, John, Esther M., Hopper, John L., Andrieu, Nadine, Noguès, Catherine, Mouret-Fourme, Emmanuelle, Lasset, Christine, Fricker, Jean-Pierre, Berthet, Pascaline, Mari, Véronique, Salle, Lucie, Schmidt, Marjanka K., Ausems, Margreet G. E. M., Garcia, Encarnacion B. Gomez, van de Beek, Irma, Wevers, Marijke R., Evans, D. Gareth, Tischkowitz, Marc, Lalloo, Fiona, Cook, Jackie, Izatt, Louise, Tripathi, Vishakha, Snape, Katie, Musgrave, Hannah, Sharif, Saba, Murray, Jennie, Colonna, Sarah V., Andrulis, Irene L., Daly, Mary B., Southey, Melissa C., de la Hoya, Miguel, Osorio, Ana, Foretova, Lenka, Berkova, Dita, Gerdes, Anne-Marie, Olah, Edith, Jakubowska, Anna, Singer, Christian F., Tan, Yen, Augustinsson, Annelie, Rantala, Johanna, Simard, Jacques, Schmutzler, Rita K., Milne, Roger L., Phillips, Kelly-Anne, Terry, Mary Beth, Goldgar, David, van Leeuwen, Flora E., Mooij, Thea M., Antoniou, Antonis C., Easton, Douglas F., Rookus, Matti A., and Engel, Christoph

Abstract

Additional file 1: Table S1. Overview of the studies contributing to the retrospective and prospective analyses.

Published
2023
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11. Additional file 5 of Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium

Author

Kast, Karin, John, Esther M., Hopper, John L., Andrieu, Nadine, Noguès, Catherine, Mouret-Fourme, Emmanuelle, Lasset, Christine, Fricker, Jean-Pierre, Berthet, Pascaline, Mari, Véronique, Salle, Lucie, Schmidt, Marjanka K., Ausems, Margreet G. E. M., Garcia, Encarnacion B. Gomez, van de Beek, Irma, Wevers, Marijke R., Evans, D. Gareth, Tischkowitz, Marc, Lalloo, Fiona, Cook, Jackie, Izatt, Louise, Tripathi, Vishakha, Snape, Katie, Musgrave, Hannah, Sharif, Saba, Murray, Jennie, Colonna, Sarah V., Andrulis, Irene L., Daly, Mary B., Southey, Melissa C., de la Hoya, Miguel, Osorio, Ana, Foretova, Lenka, Berkova, Dita, Gerdes, Anne-Marie, Olah, Edith, Jakubowska, Anna, Singer, Christian F., Tan, Yen, Augustinsson, Annelie, Rantala, Johanna, Simard, Jacques, Schmutzler, Rita K., Milne, Roger L., Phillips, Kelly-Anne, Terry, Mary Beth, Goldgar, David, van Leeuwen, Flora E., Mooij, Thea M., Antoniou, Antonis C., Easton, Douglas F., Rookus, Matti A., and Engel, Christoph

Abstract

Additional file 5: Table S5. Weight versus body mass index and breast cancer risk in BRCA1 and BRCA2 variant carriers, by menopausal status.

Published
2023
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12. Additional file 2 of Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium

Author

Kast, Karin, John, Esther M., Hopper, John L., Andrieu, Nadine, Noguès, Catherine, Mouret-Fourme, Emmanuelle, Lasset, Christine, Fricker, Jean-Pierre, Berthet, Pascaline, Mari, Véronique, Salle, Lucie, Schmidt, Marjanka K., Ausems, Margreet G. E. M., Garcia, Encarnacion B. Gomez, van de Beek, Irma, Wevers, Marijke R., Evans, D. Gareth, Tischkowitz, Marc, Lalloo, Fiona, Cook, Jackie, Izatt, Louise, Tripathi, Vishakha, Snape, Katie, Musgrave, Hannah, Sharif, Saba, Murray, Jennie, Colonna, Sarah V., Andrulis, Irene L., Daly, Mary B., Southey, Melissa C., de la Hoya, Miguel, Osorio, Ana, Foretova, Lenka, Berkova, Dita, Gerdes, Anne-Marie, Olah, Edith, Jakubowska, Anna, Singer, Christian F., Tan, Yen, Augustinsson, Annelie, Rantala, Johanna, Simard, Jacques, Schmutzler, Rita K., Milne, Roger L., Phillips, Kelly-Anne, Terry, Mary Beth, Goldgar, David, van Leeuwen, Flora E., Mooij, Thea M., Antoniou, Antonis C., Easton, Douglas F., Rookus, Matti A., and Engel, Christoph

Abstract

Additional file 2: Table S2. Retrospective and prospective analysis of height in quintiles and breast cancer risk, by menopausal status.

Published
2023
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13. Additional file 4 of Associations of height, body mass index, and weight gain with breast cancer risk in carriers of a pathogenic variant in BRCA1 or BRCA2: the BRCA1 and BRCA2 Cohort Consortium

Author

Kast, Karin, John, Esther M., Hopper, John L., Andrieu, Nadine, Noguès, Catherine, Mouret-Fourme, Emmanuelle, Lasset, Christine, Fricker, Jean-Pierre, Berthet, Pascaline, Mari, Véronique, Salle, Lucie, Schmidt, Marjanka K., Ausems, Margreet G. E. M., Garcia, Encarnacion B. Gomez, van de Beek, Irma, Wevers, Marijke R., Evans, D. Gareth, Tischkowitz, Marc, Lalloo, Fiona, Cook, Jackie, Izatt, Louise, Tripathi, Vishakha, Snape, Katie, Musgrave, Hannah, Sharif, Saba, Murray, Jennie, Colonna, Sarah V., Andrulis, Irene L., Daly, Mary B., Southey, Melissa C., de la Hoya, Miguel, Osorio, Ana, Foretova, Lenka, Berkova, Dita, Gerdes, Anne-Marie, Olah, Edith, Jakubowska, Anna, Singer, Christian F., Tan, Yen, Augustinsson, Annelie, Rantala, Johanna, Simard, Jacques, Schmutzler, Rita K., Milne, Roger L., Phillips, Kelly-Anne, Terry, Mary Beth, Goldgar, David, van Leeuwen, Flora E., Mooij, Thea M., Antoniou, Antonis C., Easton, Douglas F., Rookus, Matti A., and Engel, Christoph

Abstract

Additional file 4: Table S4. Prospective analysis of associations between height, body mass index, weight change and breast cancer risk, by menopausal status.

Published
2023
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14. PREDICT validity for prognosis of breast cancer patients with pathogenic BRCA1/2 variants

Author

Muranen, Taru, primary, Morra, Anna, additional, Khan, Sofia, additional, Barnes, Daniel, additional, Bolla, Manjeet, additional, Dennis, Joe, additional, Keeman, Renske, additional, Leslie, Goska, additional, Parsons, Michael, additional, Wang, Qin, additional, Ahearn, Thomas, additional, Aittomäki, Kristiina, additional, Andrulis, Irene, additional, Arun, Banu, additional, Behrens, Sabine, additional, Białkowska, Katarzyna, additional, Bojesen, Stig, additional, Camp, Nicola, additional, Chang-Claude, Jenny, additional, Czene, Kamila, additional, Devilee, Peter, additional, Domchek, Susan, additional, Dunning, Alison, additional, Engel, Christoph, additional, Evans, Gareth, additional, Gago-Dominguez, Manuela, additional, Garcia-Closas, Montserrat, additional, Gerdes, Anne-Marie, additional, Glendon, Gord, additional, Guénel, Pascal, additional, Hahnen, Eric, additional, Hamann, Prof U., additional, Hanson, Helen, additional, Hooning, Maartje, additional, Hoppe, Reiner, additional, Izatt, Louise, additional, Jakubowska, Anna, additional, James, Paul, additional, Kristensen, Vessela, additional, Lalloo, Fiona, additional, Lindeman, Geoffrey, additional, Mannermaa, Arto, additional, Margolin, Sara, additional, Neuhausen, Susan, additional, Newman, William, additional, Peterlongo, Paolo, additional, Phillips, Kelly-Anne, additional, Pujana, Miquel Angel, additional, Rantala, Johann, additional, Rønlund, Karina, additional, Saloustros, Emmanouil, additional, Schmutzler, Rita, additional, schneeweiss, andreas, additional, Singer, Christian, additional, Suvanto, Maija, additional, Tan, Yen Yen, additional, Teixeira, Manuel, additional, Thomassen, Mads, additional, Tischkowitz, Marc, additional, Tripathi, Vishakha, additional, Wappenschmidt, Barbara, additional, Zhao, Emily, additional, Easton, Douglas, additional, Antoniou, Antonis, additional, Chenevix-Trench, Georgia, additional, Pharoah, Paul, additional, Schmidt, Marjanka, additional, Blomqvist, Carl, additional, and Nevanlinna, Heli, additional

Published
2022
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15. The genetic counsellor role in the United Kingdom

Author

Middleton, Anna, primary, Taverner, Nicola, additional, Moreton, Natalie, additional, Rizzo, Roberta, additional, Houghton, Catherine, additional, Watt, Catherine, additional, Horton, Esther, additional, Levene, Sara, additional, Leonard, Phil, additional, Melville, Athalie, additional, Ellis, Somya, additional, Tripathi, Vishakha, additional, Patch, Christine, additional, and Jenkins, Elaine, additional

Published
2022
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16. The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants inBRCA1andBRCA2

Author

Philpott, Sue, primary, Raikou, Maria, additional, Manchanda, Ranjit, additional, Lockley, Michelle, additional, Singh, Naveena, additional, Scott, Malcolm, additional, Evans, D Gareth, additional, Adlard, Julian, additional, Ahmed, Munaza, additional, Edmondson, Richard, additional, Woodward, Emma Roisin, additional, Lamnisos, Athena, additional, Balega, Janos, additional, Brady, Angela F, additional, Sharma, Aarti, additional, Izatt, Louise, additional, Kulkarni, Anjana, additional, Tripathi, Vishakha, additional, Solomons, Joyce S, additional, Hayes, Kevin, additional, Hanson, Helen, additional, Snape, Katie, additional, Side, Lucy, additional, Skates, Steve, additional, McGuire, Alistair, additional, and Rosenthal, Adam N, additional

Published
2022
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18. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, Daniel R, Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A, Ahmed, Munaza, Aittomäki, Kristiina, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E, Borg, Åke, Bozsik, Aniko, Brady, Angela F, Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen BM, GEMO Study Collaborators, EMBRACE Collaborators, Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesús, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D Gareth, Feliubadaló, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas VO, Hanson, Helen, Hentschel, Julia, Horvath, Judit, KConFab Investigators, HEBON Investigators, Izatt, Louise, Izquierdo, Angel, James, Paul A, Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M, Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A, Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernández, Adria, Mai, Phuong L, Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N, Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N, Morrison, Patrick J, Muranen, Taru A, Murray, Alex, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nguyen-Dumont, Tu, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo I, Palli, Domenico, Parsons, Michael T, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H, Pinto, Pedro, Porteous, Mary E, Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T, Rønlund, Karina, Rump, Andreas, Sánchez de Abajo, Ana María, Shah, Payal D, Sharif, Saba, Side, Lucy E, Singer, Christian F, Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R, Teulé, Alex, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tommasi, Stefania, Toss, Angela, Trainer, Alison H, Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J, Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J, Schmutzler, Rita K, Simard, Jacques, Easton, Douglas F, Chenevix-Trench, Georgia, Antoniou, Antonis C, Ottini, Laura, Consortium of Investigators of Modifiers of BRCA1 and BRCA2, Barnes, Daniel R [0000-0002-3781-7570], Silvestri, Valentina [0000-0003-0712-9379], Leslie, Goska [0000-0001-5756-6222], Dennis, Joe [0000-0003-4591-1214], Yang, Xin [0000-0003-0037-3790], Adlard, Julian [0000-0002-1693-0435], Agnarsson, Bjarni A [0000-0001-7721-9965], Andrulis, Irene L [0000-0002-4226-6435], Arason, Adalgeir [0000-0003-0480-886X], Arnold, Norbert [0000-0003-4523-8808], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Barkardottir, Rosa B [0000-0003-0629-2772], Barrowdale, Daniel [0000-0003-1661-3939], Benitez, Javier [0000-0002-0923-7202], Boonen, Susanne E [0000-0002-7824-2080], Bozsik, Aniko [0000-0001-5410-9173], Brennan, Paul [0000-0003-1128-6254], Brunet, Joan [0000-0003-1945-3512], Bucalo, Agostino [0000-0003-3475-1067], Caligo, Maria A [0000-0003-0589-1829], Campbell, Ian [0000-0002-7773-4155], Cassingham, Hayley [0000-0001-9922-2321], Cini, Giulia [0000-0002-8696-8922], Claes, Kathleen BM [0000-0003-0841-7372], Coppa, Anna [0000-0001-9758-5444], Cortesi, Laura [0000-0001-8950-8561], Darder, Esther [0000-0002-7764-1397], de la Hoya, Miguel [0000-0002-8113-1410], de Putter, Robin [0000-0001-9410-8941], Del Valle, Jesús [0000-0003-3607-7045], Domchek, Susan M [0000-0002-5914-7272], Donaldson, Alan [0000-0001-9193-4172], Eason, Jacqueline [0000-0002-8711-8671], Engel, Christoph [0000-0002-7247-282X], Fostira, Florentia [0000-0003-2751-2332], Frone, Megan [0000-0001-8273-8866], Glendon, Gord [0000-0001-8630-6673], Godwin, Andrew K [0000-0002-3987-9580], Greene, Mark H [0000-0003-1852-9239], Hahnen, Eric [0000-0003-2448-7872], Hanson, Helen [0000-0002-3303-8713], Izatt, Louise [0000-0003-1258-4843], Izquierdo, Angel [0000-0003-2004-3246], James, Paul A [0000-0002-4361-4657], John, Esther M [0000-0003-3259-8003], Kroeldrup, Lone [0000-0003-3623-6536], Kruse, Torben A [0000-0002-2460-6483], Lazaro, Conxi [0000-0002-7198-5906], Lesueur, Fabienne [0000-0001-7404-4549], Matrai, Zoltan [0000-0001-8160-7100], Montagna, Marco [0000-0002-4929-2150], Monteiro, Alvaro N [0000-0002-8448-4801], Morrison, Patrick J [0000-0002-2823-1762], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Neuhausen, Susan L [0000-0001-5053-0390], Nevanlinna, Heli [0000-0002-0916-2976], Nguyen-Dumont, Tu [0000-0002-6217-0182], Niederacher, Dieter [0000-0001-6231-9226], Palli, Domenico [0000-0002-5558-2437], Parsons, Michael T [0000-0003-3242-8477], Perez-Segura, Pedro [0000-0001-5049-7199], Peterlongo, Paolo [0000-0001-6951-6855], Pinto, Pedro [0000-0001-6289-5792], Pottinger, Caroline [0000-0003-4233-882X], Radice, Paolo [0000-0001-6298-4111], Robson, Mark [0000-0002-3109-1692], Rump, Andreas [0000-0001-7116-6364], Sharif, Saba [0000-0002-9564-4890], Steele, Linda [0000-0003-3628-2022], Stoppa-Lyonnet, Dominique [0000-0002-5438-8309], Teixeira, Manuel R [0000-0002-4896-5982], Thull, Darcy L [0000-0001-7999-2804], Tischkowitz, Marc [0000-0002-7880-0628], Toland, Amanda E [0000-0002-0271-1792], Tommasi, Stefania [0000-0002-2157-2978], Toss, Angela [0000-0002-1854-6701], Tripathi, Vishakha [0000-0001-8118-8364], Valentini, Virginia [0000-0003-3393-7185], van Asperen, Christi J [0000-0002-1436-7650], Venturelli, Marta [0000-0003-0658-8004], Viel, Alessandra [0000-0003-2804-0840], Vijai, Joseph [0000-0002-7933-151X], Whaite, Anna [0000-0003-4485-0341], Simard, Jacques [0000-0001-6906-3390], Easton, Douglas F [0000-0003-2444-3247], Chenevix-Trench, Georgia [0000-0002-1878-2587], Ottini, Laura [0000-0001-8030-0449], and Apollo - University of Cambridge Repository

Subjects
Aged, 80 and over, BRCA2 Protein, Male, Heterozygote, BRCA1 Protein, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Mutation, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases
Abstract

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Published
2022

19. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, Daniel R., Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E., Borg, Ake, Bozsik, Aniko, Brady, Angela F., Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen B. M., Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesus, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D. Gareth, Feliubadalo, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hanson, Helen, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M., Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A., Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernandez, Adria, Mai, Phuong L., Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N., Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N., Morrison, Patrick J., Muranen, Taru A., Murray, Alex, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo, I, Palli, Domenico, Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H., Pinto, Pedro, Porteous, Mary E., Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T., Ronlund, Karina, Rump, Andreas, Sanchez de Abajo, Ana Maria, Shah, Payal D., Sharif, Saba, Side, Lucy E., Singer, Christian F., Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tommasi, Stefania, Toss, Angela, Trainer, Alison H., Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J., Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J., Schmutzler, Rita K., Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., Ottini, Laura, Barnes, Daniel R., Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A., Ahmed, Munaza, Aittomaki, Kristiina, Andrulis, Irene L., Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmana, Judith, Barkardottir, Rosa B., Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E., Borg, Ake, Bozsik, Aniko, Brady, Angela F., Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen B. M., Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, de la Hoya, Miguel, De Leeneer, Kim, de Putter, Robin, Del Valle, Jesus, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D. Gareth, Feliubadalo, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K., Goldgar, David E., Greene, Mark H., Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas V. O., Hanson, Helen, Hentschel, Julia, Horvath, Judit, Izatt, Louise, Izquierdo, Angel, James, Paul A., Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M., Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A., Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernandez, Adria, Mai, Phuong L., Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N., Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N., Morrison, Patrick J., Muranen, Taru A., Murray, Alex, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo, I, Palli, Domenico, Parsons, Michael T., Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H., Pinto, Pedro, Porteous, Mary E., Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T., Ronlund, Karina, Rump, Andreas, Sanchez de Abajo, Ana Maria, Shah, Payal D., Sharif, Saba, Side, Lucy E., Singer, Christian F., Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R., Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tommasi, Stefania, Toss, Angela, Trainer, Alison H., Tripathi, Vishakha, Valentini, Virginia, van Asperen, Christi J., Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J., Schmutzler, Rita K., Simard, Jacques, Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., and Ottini, Laura

Abstract

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

Published
2022

20. The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2.

Author

Philpott, Sue, Raikou, Maria, Manchanda, Ranjit, Lockley, Michelle, Singh, Naveena, Scott, Malcolm, Evans, D. Gareth, Adlard, Julian, Ahmed, Munaza, Edmondson, Richard, Woodward, Emma Roisin, Lamnisos, Athena, Balega, Janos, Brady, Angela F., Sharma, Aarti, Izatt, Louise, Kulkarni, Anjana, Tripathi, Vishakha, Solomons, Joyce S., and Hayes, Kevin

Abstract

Background Our study aimed to establish ’real-world’ performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). Methods Our study recruited 875 female BRCA1/2- heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. Results Our study identified 8 OCs during 1277women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9–100), 75% (34.9–96.8) and 99.9% (99.9–100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER costsaving of -£102,496/QALY. Conclusion OC surveillance for women deferring RRSO in a ’real-world’ setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery. [ABSTRACT FROM AUTHOR]

Published
2023
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21. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study

Author

Bancroft, Elizabeth K, primary, Page, Elizabeth C, additional, Brook, Mark N, additional, Thomas, Sarah, additional, Taylor, Natalie, additional, Pope, Jennifer, additional, McHugh, Jana, additional, Jones, Ann-Britt, additional, Karlsson, Questa, additional, Merson, Susan, additional, Ong, Kai Ren, additional, Hoffman, Jonathan, additional, Huber, Camilla, additional, Maehle, Lovise, additional, Grindedal, Eli Marie, additional, Stormorken, Astrid, additional, Evans, D Gareth, additional, Rothwell, Jeanette, additional, Lalloo, Fiona, additional, Brady, Angela F, additional, Bartlett, Marion, additional, Snape, Katie, additional, Hanson, Helen, additional, James, Paul, additional, McKinley, Joanne, additional, Mascarenhas, Lyon, additional, Syngal, Sapna, additional, Ukaegbu, Chinedu, additional, Side, Lucy, additional, Thomas, Tessy, additional, Barwell, Julian, additional, Teixeira, Manuel R, additional, Izatt, Louise, additional, Suri, Mohnish, additional, Macrae, Finlay A, additional, Poplawski, Nicola, additional, Chen-Shtoyerman, Rakefet, additional, Ahmed, Munaza, additional, Musgrave, Hannah, additional, Nicolai, Nicola, additional, Greenhalgh, Lynn, additional, Brewer, Carole, additional, Pachter, Nicholas, additional, Spigelman, Allan D, additional, Azzabi, Ashraf, additional, Helfand, Brian T, additional, Halliday, Dorothy, additional, Buys, Saundra, additional, Ramon y Cajal, Teresa, additional, Donaldson, Alan, additional, Cooney, Kathleen A, additional, Harris, Marion, additional, McGrath, John, additional, Davidson, Rosemarie, additional, Taylor, Amy, additional, Cooke, Peter, additional, Myhill, Kathryn, additional, Hogben, Matthew, additional, Aaronson, Neil K, additional, Ardern-Jones, Audrey, additional, Bangma, Chris H, additional, Castro, Elena, additional, Dearnaley, David, additional, Dias, Alexander, additional, Dudderidge, Tim, additional, Eccles, Diana M, additional, Green, Kate, additional, Eyfjord, Jorunn, additional, Falconer, Alison, additional, Foster, Christopher S, additional, Gronberg, Henrik, additional, Hamdy, Freddie C, additional, Johannsson, Oskar, additional, Khoo, Vincent, additional, Lilja, Hans, additional, Lindeman, Geoffrey J, additional, Lubinski, Jan, additional, Axcrona, Karol, additional, Mikropoulos, Christos, additional, Mitra, Anita V, additional, Moynihan, Clare, additional, Ni Raghallaigh, Holly, additional, Rennert, Gad, additional, Collier, Rebecca, additional, Offman, Judith, additional, Kote-Jarai, Zsofia, additional, Eeles, Rosalind A, additional, Adams, Lisa, additional, Adlard, Julian, additional, Alfonso, Rosa, additional, Ali, Saira, additional, Andrew, Angela, additional, Araújo, Luís, additional, Azam, Nazya, additional, Ball, Darran, additional, Barker, Queenstone, additional, Basevitch, Alon, additional, Benton, Barbara, additional, Berlin, Cheryl, additional, Bermingham, Nicola, additional, Biller, Leah, additional, Bloss, Angela, additional, Bradford, Matilda, additional, Bradshaw, Nicola, additional, Branson, Amy, additional, Brendler, Charles, additional, Brennan, Maria, additional, Bulman, Barbara, additional, Burgess, Lucy, additional, Cahill, Declan, additional, Callard, Alice, additional, Calvo Verges, Nuria, additional, Cardoso, Marta, additional, Carter, Vanda, additional, Catanzaro, Mario, additional, Chamberlain, Anthony, additional, Chapman, Cyril, additional, Chong, Michael, additional, Clark, Caroline, additional, Clowes, Virginia, additional, Cogley, Lyn, additional, Cole, Trevor, additional, Compton, Cecilia, additional, Conner, Tom, additional, Cookson, Sandra, additional, Cornford, Philip, additional, Costello, Philandra, additional, Coulier, Laura, additional, Davies, Michaela, additional, Dechet, Christopher, additional, DeSouza, Bianca, additional, Devlin, Gemma, additional, Douglas, Fiona, additional, Douglas, Emma, additional, Dudakia, Darshna, additional, Duncan, Alexis, additional, Ellery, Natalie, additional, Everest, Sarah, additional, Freemantle, Sue, additional, Frydenberg, Mark, additional, Fuller, Debbie, additional, Gabriel, Camila, additional, Gale, Madeline, additional, Garcia, Lynda, additional, Gay, Simona, additional, Genova, Elena, additional, George, Angela, additional, Georgiou, Demetra, additional, Gisbert, Alexandra, additional, Gleeson, Margaret, additional, Glover, Wayne, additional, Gnanapragasam, Vincent, additional, Goff, Sally, additional, Goldgar, David, additional, Gonçalves, Nuno, additional, Goodman, Selina, additional, Gorrie, Jennifer, additional, Gott, Hannah, additional, Grant, Anna, additional, Gray, Catherine, additional, Griffiths, Julie, additional, Gupwell, Karin, additional, Gurasashvili, Jana, additional, Hanslien, Eldbjørg, additional, Haraldsdottir, Sigurdis, additional, Hart, Rachel, additional, Hartigan, Catherine, additional, Hawkes, Lara, additional, Heaton, Tricia, additional, Henderson, Alex, additional, Henrique, Rui, additional, Hilario, Kathrine, additional, Hill, Kathryn, additional, Hulick, Peter, additional, Hunt, Clare, additional, Hutchings, Melanie, additional, Ibitoye, Rita, additional, Inglehearn, Thomas, additional, Ireland, Joanna, additional, Islam, Farah, additional, Ismail, Siti, additional, Jacobs, Chris, additional, James, Denzil, additional, Jenkins, Sharon, additional, Jobson, Irene, additional, Johnstone, Anne, additional, Jones, Oliver, additional, Josefsberg Ben-Yehoshua, Sagi, additional, Kaemba, Beckie, additional, Kaul, Karen, additional, Kemp, Zoe, additional, Kinsella, Netty, additional, Klehm, Margaret, additional, Kockelbergh, Roger, additional, Kohut, Kelly, additional, Kosicka-Slawinska, Monika, additional, Kulkarni, Anjana, additional, Kumar, Pardeep, additional, Lam, Jimmy, additional, LeButt, Mandy, additional, Leibovici, Dan, additional, Lim, Ramona, additional, Limb, Lauren, additional, Lomas, Claire, additional, Longmuir, Mark, additional, López, Consol, additional, Magnani, Tiziana, additional, Maia, Sofia, additional, Maiden, Jessica, additional, Male, Alison, additional, Manalo, Merrie, additional, Martin, Phoebe, additional, McBride, Donna, additional, McGuire, Michael, additional, McMahon, Romayne, additional, McNally, Claire, additional, McVeigh, Terri, additional, Melzer, Ehud, additional, Mencias, Mark, additional, Mercer, Catherine, additional, Mitchell, Gillian, additional, Mora, Josefina, additional, Morton, Catherine, additional, Moss, Cathryn, additional, Murphy, Morgan, additional, Murphy, Declan, additional, Mzazi, Shumi, additional, Nadolski, Maria, additional, Newlin, Anna, additional, Nogueira, Pedro, additional, O'Keefe, Rachael, additional, O'Toole, Karen, additional, O'Connell, Shona, additional, Ogden, Chris, additional, Okoth, Linda, additional, Oliveira, Jorge, additional, Paez, Edgar, additional, Palou, Joan, additional, Park, Linda, additional, Patel, Nafisa, additional, Paulo Souto, João, additional, Pearce, Allison, additional, Peixoto, Ana, additional, Perez, Kimberley, additional, Petelin, Lara, additional, Pichert, Gabriella, additional, Poile, Charlotte, additional, Potter, Alison, additional, Preitner, Nadia, additional, Purnell, Helen, additional, Quinn, Ellen, additional, Radice, Paolo, additional, Rankin, Brigette, additional, Rees, Katie, additional, Renton, Caroline, additional, Richardson, Kate, additional, Risby, Peter, additional, Rogers, Jason, additional, Ruderman, Maggie, additional, Ruiz, April, additional, Sajoo, Anaar, additional, Salvatore, Natale, additional, Sands, Victoria, additional, Sanguedolce, Francesco, additional, Sattar, Ayisha, additional, Saunders, Kathryn, additional, Schofield, Lyn, additional, Scott, Rodney, additional, Searle, Anne, additional, Sehra, Ravinder, additional, Selkirk, Christina, additional, Shackleton, Kylie, additional, Shanley, Sue, additional, Shaw, Adam, additional, Shevrin, Daniel, additional, Shipman, Hannah, additional, Sidat, Zahirah, additional, Siguake, Kas, additional, Simon, Kate, additional, Smyth, Courtney, additional, Snadden, Lesley, additional, Solanky, Nita, additional, Solomons, Joyce, additional, Sorrentino, Margherita, additional, Stayner, Barbara, additional, Stephenson, Robert, additional, Stoffel, Elena, additional, Thomas, Maggie, additional, Thompson, Alan, additional, Tidey, Lizzie, additional, Tischkowitz, Marc, additional, Torokwa, Audrey, additional, Townshend, Sharron, additional, Treherne, Katy, additional, Tricker, Karen, additional, Trinh, Quoc-Dien, additional, Tripathi, Vishakha, additional, Turnbull, Clare, additional, Valdagni, Riccardo, additional, Van As, Nicholas, additional, Venne, Vickie, additional, Verdon, Lizzie, additional, Vitellaro, Marco, additional, Vogel, Kristen, additional, Walker, Lisa, additional, Watford, Amy, additional, Watt, Cathy, additional, Weintroub, Ilana, additional, Weiss, Shelly, additional, Weissman, Scott, additional, Weston, Michelle, additional, Wiggins, Jennifer, additional, Wise, Gillian, additional, Woodhouse, Christopher, additional, Yesildag, Pembe, additional, Youngs, Alice, additional, Yurgelun, Matthew, additional, and Zollo, Fabiana, additional

Published
2021
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23. The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1and BRCA2

Author

Philpott, Sue, Raikou, Maria, Manchanda, Ranjit, Lockley, Michelle, Singh, Naveena, Scott, Malcolm, Evans, D Gareth, Adlard, Julian, Ahmed, Munaza, Edmondson, Richard, Woodward, Emma Roisin, Lamnisos, Athena, Balega, Janos, Brady, Angela F, Sharma, Aarti, Izatt, Louise, Kulkarni, Anjana, Tripathi, Vishakha, Solomons, Joyce S, Hayes, Kevin, Hanson, Helen, Snape, Katie, Side, Lucy, Skates, Steve, McGuire, Alistair, and Rosenthal, Adam N

Abstract

BackgroundOur study aimed to establish ‘real-world’ performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO).MethodsOur study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation.ResultsOur study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9–100), 75% (34.9–96.8) and 99.9% (99.9–100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY.ConclusionOC surveillance for women deferring RRSO in a ‘real-world’ setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.

Published
2023
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24. 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, Hassan Al Battat, Mona, Thomas, Sarah, Taylor, Natalie, Chamberlain, Anthony, Pope, Jennifer, Raghallaigh, Holly Ni, 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 Dyrsø, 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, Feliubadaló, 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, Cardoso, Marta, Human Genetics, Targeted Gynaecologic Oncology (TARGON), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)

Subjects
CANCER MORTALITY, Prostate cancer, endocrine system diseases, PREDICTION, Targeted prostate screening, MEN, OVARIAN, urologic and male genital diseases, BRCA1, BREAST, BRCA2, Prostate-specific-antigen, INCREASE, ERSPC, SURVIVAL, TRIAL, skin and connective tissue diseases
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 biopsy than PSA alone (AUC = 0.65).CONCLUSIONS: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers.PATIENT SUMMARY: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening.

Published
2019

25. 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, Raghallaigh, Holly Ni, 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-Stamsm, 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, van den Enden, Apollonia T. J. M. Helderman, Eeles, Rosalind A., MUMC+: DA KG Polikliniek (9), and RS: GROW - R4 - Reproductive and Perinatal Medicine

Subjects
CANCER MORTALITY, Prostate cancer, Targeted prostate screening, PREDICTION, MEN, BRCA1, OVARIAN, BRCA2, Prostate-specific-antigen, BREAST, INCREASE, ERSPC, SURVIVAL, TRIAL
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 biopsy than PSA alone (AUC = 0.65). Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. Patient summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening. (C) 2019 The Authors. Published by Elsevier B.V.

Published
2019

28. Prostate Cancer Risk by BRCA2 Genomic Regions

Author

Nyberg, Tommy, primary, Frost, Debra, additional, Barrowdale, Daniel, additional, Evans, D. Gareth, additional, Bancroft, Elizabeth, additional, Adlard, Julian, additional, Ahmed, Munaza, additional, Barwell, Julian, additional, Brady, Angela F., additional, Brewer, Carole, additional, Cook, Jackie, additional, Davidson, Rosemarie, additional, Donaldson, Alan, additional, Eason, Jacqueline, additional, Gregory, Helen, additional, Henderson, Alex, additional, Izatt, Louise, additional, Kennedy, M. John, additional, Miller, Claire, additional, Morrison, Patrick J., additional, Murray, Alex, additional, Ong, Kai-Ren, additional, Porteous, Mary, additional, Pottinger, Caroline, additional, Rogers, Mark T., additional, Side, Lucy, additional, Snape, Katie, additional, Tripathi, Vishakha, additional, Walker, Lisa, additional, Tischkowitz, Marc, additional, Eeles, Rosalind, additional, Easton, Douglas F., additional, and Antoniou, Antonis C., additional

Published
2020
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29. 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

30. 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

31. An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Author

Blein, Sophie, Bardel, Claire, Danjean, Vincent, Mcguffog, Lesley, Healey, Sue, Barrowdale, Daniel, Lee, Andrew, Dennis, Joe, Kuchenbaecker, Karoline B., Soucy, Penny, Terry, Mary Beth, Chung, Wendy K., Goldgar, David E., Buys, Saundra S., Janavicius, Ramunas, Tihomirova, Laima, Tung, Nadine, Dorfling, Cecilia M., van Rensburg, Elizabeth J., Neuhausen, Susan L., Ding, Yuan Chun, Gerdes, Anne Marie, Ejlertsen, Bent, Nielsen, Finn C., Hansen, Thomas V. O., Osorio, Ana, Benitez, Javier, Conejero, Raquel Andrés, Segota, Ena, Weitzel, Jeffrey N., Thelander, Margo, Peterlongo, Paolo, Radice, Paolo, Pensotti, Valeria, Dolcetti, Riccardo, Bonanni, Bernardo, Peissel, Bernard, Zaffaroni, Daniela, Scuvera, Giulietta, Manoukian, Siranoush, Varesco, Liliana, Capone, Gabriele L., Papi, Laura, Ottini, Laura, Yannoukakos, Drakoulis, Konstantopoulou, Irene, Garber, Judy, Hamann, Ute, Donaldson, Alan, Brady, Angela, Brewer, Carole, Foo, Claire, Evans, D. Gareth, Frost, Debra, Eccles, Diana, Douglas, Fiona, Cook, Jackie, Adlard, Julian, Barwell, Julian, Walker, Lisa, Izatt, Louise, Side, Lucy E., Kennedy, M. John, Tischkowitz, Marc, Rogers, Mark T., Porteous, Mary E., Morrison, Patrick J., Platte, Radka, Eeles, Ros, Davidson, Rosemarie, Hodgson, Shirley, Cole, Trevor, Godwin, Andrew K., Isaacs, Claudine, Claes, Kathleen, De Leeneer, Kim, Meindl, Alfons, Gehrig, Andrea, Wappenschmidt, Barbara, Sutter, Christian, Engel, Christoph, Niederacher, Dieter, Steinemann, Doris, Plendl, Hansjoerg, Kast, Karin, Rhiem, Kerstin, Ditsch, Nina, Arnold, Norbert, Varon Mateeva, Raymonda, Schmutzler, Rita K., Preisler Adams, Sabine, Markov, Nadja Bogdanova, Wang Gohrke, Shan, de Pauw, Antoine, Lefol, Cédrick, Lasset, Christine, Leroux, Dominique, Rouleau, Etienne, Damiola, Francesca, Dreyfus, Hélène, Barjhoux, Laure, Golmard, Lisa, Uhrhammer, Nancy, Bonadona, Valérie, Sornin, Valérie, Bignon, Yves Jean, Carter, Jonathan, Van Le, Linda, Piedmonte, Marion, Disilvestro, Paul A., de la Hoya, Miguel, Caldes, Trinidad, Nevanlinna, Heli, Aittomäki, Kristiina, Jager, Agnes, van den Ouweland, Ans M. W., Kets, Carolien M., Aalfs, Cora M., van Leeuwen, Flora E., Hogervorst, Frans B. L., Meijers Heijboer, Hanne E. J., Oosterwijk, Jan C., van Roozendaal, Kees E. P., Rookus, Matti A., Devilee, Peter, van der Luijt, Rob B., Olah, Edith, Diez, Orland, Teulé, Alex, Lazaro, Conxi, Blanco, Ignacio, Del Valle, Jesús, Jakubowska, Anna, Sukiennicki, Grzegorz, Gronwald, Jacek, Lubinski, Jan, Durda, Katarzyna, Jaworska Bieniek, Katarzyna, Agnarsson, Bjarni A., Maugard, Christine, Amadori, Alberto, Montagna, Marco, Teixeira, Manuel R., Spurdle, Amanda B., Foulkes, William, Olswold, Curtis, Lindor, Noralane M., Pankratz, Vernon S., Szabo, Csilla I., Lincoln, Anne, Jacobs, Lauren, Corines, Marina, Robson, Mark, Vijai, Joseph, Berger, Andreas, Fink Retter, Anneliese, Singer, Christian F., Rappaport, Christine, Kaulich, Daphne Geschwantler, Pfeiler, Georg, Tea, Muy Kheng, Greene, Mark H., Mai, Phuong L., Rennert, Gad, Imyanitov, Evgeny N., Mulligan, Anna Marie, Glendon, Gord, Andrulis, Irene L., Tchatchou, Sandrine, Toland, Amanda Ewart, Pedersen, Inge Sokilde, Thomassen, Mads, Kruse, Torben A., Jensen, Uffe Birk, Caligo, Maria A., Friedman, Eitan, Zidan, Jamal, Laitman, Yael, Lindblom, Annika, Melin, Beatrice, Arver, Brita, Loman, Niklas, Rosenquist, Richard, Olopade, Olufunmilayo I., Nussbaum, Robert L., Ramus, Susan J., Nathanson, Katherine L., Domchek, Susan M., Rebbeck, Timothy R., Arun, Banu K., Mitchell, Gillian, Karlan, Beth Y., Lester, Jenny, Orsulic, Sandra, Stoppa Lyonnet, Dominique, Thomas, Gilles, Simard, Jacques, Couch, Fergus J., Offit, Kenneth, Easton, Douglas F., Chenevix Trench, Georgia, Antoniou, Antonis C., Mazoyer, Sylvie, Phelan, Catherine M., Sinilnikova, Olga M., Cox, David G., Angelakos, Maggie, Maskiell, Judi, Dite, Gillian, Tsimiklis, Helen, Rudaitis, Vilius, Griškevicius, Laimonas, Eglitis, Drs Janis, Krilova, Anna, Stengrevics, Aivars, Ding, Chun, Steele, Linda, Barroso, Alicia, Alonso, Rosario, Pita, Guillermo, Viel, Alessandra, della Puppa, Lara, Barile, Monica, Tommasi, Stefania, Pilato, Brunella, Lambo, Rossana, Martayan, Aline, Tibiletti, Maria Grazia, Ellis, Steve, Fineberg, Elena, Miedzybrodzka, Zosia, Gregory, Helen, Jeffers, Lisa, Ong, Kai Ren, Hoffman, Jonathan, James, Margaret, Paterson, Joan, Taylor, Amy, Murray, Alexandra, Mccann, Emma, Barton, David, Drummond, Sarah, Kivuva, Emma, Searle, Anne, Goodman, Selina, Hill, Kathryn, Murday, Victoria, Bradshaw, Nicola, Snadden, Lesley, Longmuir, Mark, Watt, Catherine, Gibson, Sarah, Haque, Eshika, Tobias, Ed, Duncan, Alexis, Jacobs, Chris, Langman, Caroline, Dorkins, Huw, Serra Feliu, Gemma, Ellis, Ian, Houghton, Catherine, Lalloo, Fiona, Taylor, Jane, Male, Alison, Berlin, Cheryl, Eason, Jacqueline, Collier, Rebecca, Claber, Oonagh, Jobson, Irene, Mcleod, Diane, Halliday, Dorothy, Durell, Sarah, Stayner, Barbara, Shanley, Susan, Rahman, Nazneen, Houlston, Richard, Bancroft, Elizabeth, Page, Elizabeth, Ardern Jones, Audrey, Kohut, Kelly, Wiggins, Jennifer, Castro, Elena, Killick, Emma, Martin, Sue, Rea, Gillian, Kulkarni, Anjana, Quarrell, Oliver, Bardsley, Cathryn, Goff, Sheila, Brice, Glen, Winchester, Lizzie, Eddy, Charlotte, Tripathi, Vishakha, Attard, Virginia, Lehmann, Anna, Lucassen, Anneke, Crawford, Gillian, Mcbride, Donna, Smalley, Sarah, Weaver, Jo Ellen, Bove, Betsy, Verny Pierre, Carole, Calender, Alain, Giraud, Sophie, Léone, Mélanie, Gauthier Villars, Marion, Buecher, Bruno, Houdayer, Claude, Moncoutier, Virginie, Belotti, Muriel, Tirapo, Carole, Bressac de Paillerets, Brigitte, Caron, Olivier, Handallou, Sandrine, Hardouin, Agnès, Berthet, Pascaline, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Eisinger, François, Coupier, Isabelle, Pujol, Pascal, Peyrat, Jean Philippe, Fournier, Joëlle, Révillion, Françoise, Vennin, Philippe, Adenis, Claude, Lidereau, Rosette, Demange, Liliane, Nogues, Catherine, Muller, Danièle, Fricker, Jean Pierre, Barouk Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Rebischung, Christine, Peysselon, Magalie, Coron, Fanny, Faivre, Laurence, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Ferrer, Sandra Fert, Frénay, Marc, Vénat Bouvet, Laurence, Delnatte, Capucine, Mortemousque, Isabelle, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Sokolowska, Johanna, Bronner, Myriam, Collonge Rame, Marie Agnès, Damette, Alexandre, Lynch, Henry T., Snyder, Carrie L., Muranen, Taru A., Blomqvist, Drs Carl, Aaltonen, Kirsimari, Erkkilä, Irja, Palola, Virpi, Verhoef, S., Schmidt, M. K., de Lange, J. L., Wijnands, R., Collée, J. M., Hooning, M. J., Seynaeve, C., van Deurzen, C. H. M., Obdeijn, I. M., van Asperen, C. J., Wijnen, J. T., Tollenaar, R. A. E. M., van Cronenburg, T. C. T. E. F., Mensenkamp, A. R., Ausems, M. G. E. M., van Os, T. A. M., Gille, J. J. P., Waisfisz, Q., Gómez Garcia, E. B., Blok, M. J., van der Hout, A. H., Mourits, M. J., de Bock, G. H., Vasen, H. F., Siesling, S., Overbeek, L. I. 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P., Gayther, Simon, Pye, Carole, Harrington, Patricia, Wozniak, Eva, Lindeman, Geoffrey, Harris, Marion, Delatycki, Martin, Sawyer, Sarah, Driessen, Rebecca, Thompson, Ella, Breast Cancer Family Registry, Null, Embrace, Null, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Medical Oncology, Clinical Genetics, Radiotherapy, MUMC+: DA KG Lab Specialisten (9), Klinische Genetica, Genetica & Celbiologie, RS: FHML non-thematic output, [ 1 ] Univ Lyon 1, Ctr Rech Cancerol Lyon, CNRS, INSERM U1052,UMR5286, F-69365 Lyon, France [ 2 ] Univ Lyon, F-69000 Lyon, France [ 3 ] Univ Lyon 1, F-69100 Villeurbanne, France [ 4 ] Univ Lyon 1, CNRS, Lab Biometrie & Biol Evolut LBBE Biometrie & Bio, UMR 5558, F-69622 Villeurbanne, France [ 5 ] Univ Grenoble Alpes, Lab Informat 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Subjects
Genetic modifiers, Dna haplogroups, endocrine system diseases, Genes, BRCA2, Genes, BRCA1, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], ADN mitocondrial, SUSCEPTIBILITY, VARIANTS, 0302 clinical medicine, Breast Cancer Family Registry, Brjóstakrabbamein, MULTIPLE, Aetiology, skin and connective tissue diseases, Phylogeny, Cancer, ddc:616, 0303 health sciences, Mutation, education.field_of_study, Variants, SINGLE-NUCLEOTIDE POLYMORPHISMS, Subclade, Mitochondrial DNA, 3. Good health, ddc, Damage, Oncology, Ovarian, 030220 oncology & carcinogenesis, DISEASES, Multiple, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Single-nucleotide polymorphism, Breast Neoplasms/genetics, EMBRACE, GEMO Study Collaborators, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Genetics, Humans, education, Cancer och onkologi, Haplotype, BRCA2, Genes, mitochondrial haplogroup T1a1, breast cancer, BRCA2, Cancer and Oncology, GENETIC MODIFIERS, Polymorphisms, Cancer Research, [SDV]Life Sciences [q-bio], medicine.disease_cause, Haplogroup, 610 Medical sciences Medicine, 3123 Gynaecology and paediatrics, Medicine and Health Sciences, 2.1 Biological and endogenous factors, OXIDATIVE STRESS, Non-U.S. Gov't, Medicine(all), Gen, BRCA1 Protein, Research Support, Non-U.S. Gov't, Cohort, OVARIAN, Mitochondria, Mitochondrial, Genes, Mitochondrial, Female, Research Article, Risk, Heterozygote, BRCA1 protein, breast neoplasms, female, genetic predisposition to disease, haplotypes, humans, phylogeny, risk, genes, BRCA2, genes, mitochondrial, heterozygote, mutation, cancer research, oncology, Population, 3122 Cancers, Oncology and Carcinogenesis, Breast Neoplasms, Biology, Research Support, Càncer de mama, Breast Cancer, medicine, Journal Article, Genetic Predisposition to Disease, ddc:610, Oncology & Carcinogenesis, HEBON, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], CONSORTIUM, African, DNA HAPLOGROUPS, Arfgengi, Haplotypes, Susceptibility, BRCA1 Protein/genetics, Human mitochondrial DNA haplogroup
Abstract

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects. European Commission Seventh Framework Program 223175: HEALTH-F2-2009-223175 Cancer Research UK C12292/A11174 C1287/A10118 C1287/A11990 C5047/A8385 National Health and Medical Research Council (NHMRC) program National Health and Medical Research Council (NHMRC) American Cancer Society Early Detection Professorship SIOP-06-258-01-COUN Intramural Research Program of the National Cancer Institute, National Institutes of Health National Cancer Institute, National Institutes of Health UM1 CA164920 Lithuania (BFBOCC-LT): Research Council of Lithuania LIG-07/2012 LSC 10.0010.08 European Social Fund 2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016 Liepaja City Council, Liepaja, Latvia Breast Cancer Research Foundation Cancer Association of South Africa (CANSA) Morris and Horowitz Families Professorship in Cancer Etiology and Outcomes Research NEYE Foundation Spanish Association against Cancer (Asociacion Espanola Contra el Cancer) AECC08 Thematic Network Cooperative Research in Cancer (Red Tematica Investigacion Cooperativa en Cancer (RTICC), Centro de Investigacion Cancer, Salamanca, Spain) RTICC 06/0020/1060 Spanish Ministry of Science and Innovation FIS PI08 1120 Fondo de Investigacion Sanitaria (FIS) SAF2010-20493 Fundacion Mutua Madrilena (FMMA) City of Hope Clinical Cancer Genetics Community Network and the Hereditary Cancer Research Registry (COH-CCGCRN) National Cancer Institute and the Office of the Director, National Institutes of Health RC4CA153828 Italian citizens Fondazione IRCCS Istituto Nazionale Tumori Italian Association for Cancer Research (AIRC) European Union (European Social Fund (ESF) Greek national funds through the "Education and Lifelong Learning" operational program of the National Strategic Reference Framework (NSRF) - Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA "Heracleitus II: Investing in knowledge society through the European Social Fund" Deutsches Krebsforschungszentrum (DKFZ) National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester, UK NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London University of Kansas Cancer Center P30 CA168524 Kansas Bioscience Authority Eminent Scholar Program Chancellors Distinguished Chair in Biomedical Sciences Professorship German Cancer Aid 109076 Center for Molecular Medicine Cologne (CMMC) Ligue National Contre le Cancer Association "Le cancer du sein, parlons-en!" Award Canadian Institutes of Health Research for the CIHR Team in Familial Risks of Breast Cancer program GOA BOF10/GOA/019 Ghent University Hospital National Cancer Institute grants to the GOG Administrative Office and Tissue Bank CA 27469 GOG Statistical and Data Center CA 37517 GOG's Cancer Prevention and Control Committee CA 101165 Instituto de Salud Carlos III (ISCIII), Madrid, Spain RD12/00369/0006 12/00539 European Regional Development Fund (Fonds europeen de developpement regional (FEDER)) funds Helsinki University Central Hospital Research Fund Academy of Finland 266528 Finnish Cancer Society Sigrid Juselius Foundation Dutch Cancer Society NKI1998-1854 NKI2004-3088 NKI2007-3756 Netherlands Organization of Scientific Research NWO 91109024 Pink Ribbon grant 110005 Biobanking and Molecular Resource Infrastructure (BBMRI) NWO 184.021.007/CP46 Hungarian Research and Technological Innovation Fund (KTIA)/Hungarian Scientific Research Fund (Orszagos Tudomanyos Kutatasi Alapprogramok (OTKA)) KTIA-OTKA CK-80745 KTIA-OTKA K-112228 Institut Catala d'Oncologia (ICO): contract grant sponsor: Asociacion Espanola Contra el Cancer Spanish Health Research Foundation Ramon Areces Foundation Instituto de Salud Carlos III (ISCIII) Catalan Health Institute Autonomous Government of Catalonia International Hereditary Cancer Center (Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland) PBZ_KBN_122/P05/2004 Icelandic Association "Walking for Breast Cancer Research" Landspitali University Hospital Research Fund Canadian Institutes of Health Research (CIHR) for the "CIHR Team in Familial Risks of Breast Cancer" program, Canadian Breast Cancer Research Alliance 019511 Ministry of Economic Development, Innovation and Export Trade PSR-SIIRI-701 Ministero della Salute and a "5 x 1,000" Istituto Oncologico Veneto grant Liga Portuguesa Contra o Cancro National Breast Cancer Foundation Queensland Cancer Fund Cancer Councils of New South Wales, Victoria, Tasmania and South Australia Cancer Foundation of Western Australia National Institutes of Health (NIH) through the National Cancer Institute (NCI) CA 116167 CA 128978 CA 176785 NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer CA116201 US Department of Defense Ovarian Cancer Idea award W81XWH-10-1-0341 Ministry of Health of the Czech Republic to Masaryk Memorial Cancer Institute MMCI 00209805 European Regional Development Fund State Budget of the Czech Republic (RECAMO) CZ. 1.05/2.1.00/03.0101 Charles University in Prague project UNCE204024 Robert and Kate Niehaus Clinical Cancer Genetics Initiative Intramural Research Program of the National Cancer Institute Westat, Inc, Rockville, MD, USA N02-CP-11019-50 N02-CP-65504 Clalit Health Services in Israel Israel Cancer Association Breast Cancer Research Foundation (BCRF), New York, NY, USA Russian Federation for Basic Research 11-04-00227 12-04-00928 12-04-01490 Federal Agency for Science and Innovations, Russia 02.740.11.0780 Ohio State University Comprehensive Cancer Center Istituto Toscano Tumori (ITT) Israeli Inherited Breast Cancer Consortium Swedish Breast Cancer Swedish Cancer Society Ralph and Marion Falk Medical Research Trust Entertainment Industry Fund National Women's Cancer Research Alliance University of California, Los Angeles Jonsson Comprehensive Cancer Center Foundation: Breast Cancer Research Foundation University of California, San Francisco Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center Cancer Research UK University of Pennsylvania: National Institutes of Health (NIH) R01 CA102776 R01 CA083855 Susan G Komen for the Cure, Basser Center for BRCA Victorian Familial Cancer Trials Group (VFCTG): Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation 5U01 CA113916 R01 CA140323 ISCIIIRETIC RD06/0020/1051 PI09/02483 PI10/01422 PI10/00748 PI13/00285 PI13/00189 2009SGR290 PI13/00189 2009SGR283 CA125183 R01 CA142996 1U01CA161032

Published
2015

33. Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk

Author

Gaudet, Mia M., Kuchenbaecker, Karoline B., Vijai, Joseph, Klein, Robert J., Kirchhoff, Tomas, McGuffog, Lesley, Barrowdale, Daniel, Dunning, Alison M., Lee, Andrew, Dennis, Joe, Healey, Sue, Dicks, Ed, Soucy, Penny, Sinilnikova, Olga M., Pankratz, Vernon S., Wang, Xianshu, Eldridge, Ronald C., Tessier, Daniel C., Vincent, Daniel, Bacot, Francois, Hogervorst, Frans B.L., Peock, Susan, Stoppa-Lyonnet, Dominique, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Peterlongo, Paolo, Schmutzler, Rita K., Nathanson, Katherine L., Piedmonte, Marion, Singer, Christian F., Thomassen, Mads, Sokolowska, Johanna, Bronner, Myriam, Hansen, Thomas V.O., Neuhausen, Susan L., Blanco, Ignacio, Greene, Mark H., Garber, Judith, Weitzel, Jeffrey N., Andrulis, Irene L., Goldgar, David E., D'Andrea, Emma, Caldes, Trinidad, Nevanlinna, Heli, Osorio, Ana, van Rensburg, Elizabeth J., Arason, Adalgeir, Rennert, Gad, van den Ouweland, Ans M.W., van der Hout, Annemarie H., Kets, Carolien M., Aalfs, Cora M., Wijnen, Juul T., Ausems, Margreet G.E.M., Frost, Debra, Ellis, Steve, Fineberg, Elena, Platte, Radka, Evans, D. Gareth, Jacobs, Chris, Adlard, Julian, Tischkowitz, Marc, Porteous, Mary, Damiola, Francesca, Golmard, Lisa, Barjhoux, Laure, Longy, Michel, Belotti, Muriel, Ferrer, Sandra Fert, Mazoyer, Sylvie, Spurdle, Amanda B., Manoukian, Siranoush, Barile, Monica, Genuardi, Maurizio, Arnold, Norbert, Meindl, Alfons, Sutter, Christian, Wappenschmidt, Barbara, Domchek, Susan M., Pfeiler, Georg, Friedman, Eitan, Jensen, Uffe Birk, Robson, Mark, Shah, Sohela, Lazaro, Conxi, Mai, Phuong L., Benitez, Javier, Southey, Melissa C., Schmidt, M. K., Fasching, Peter A., Peto, Julian, Humphreys, Manjeet K., Wang, Qin, Michailidou, Kyriaki, Sawyer, Elinor J., Burwinkel, Barbara, Guénel, Pascal, Bojesen, Stig E., Milne, Roger L., Brenner, Hermann, Lochmann, Magdalena, Brauch, Hiltrud, Ko, Yon Dschun, Baisch, Christian, Fischer, Hand Peter, Bruening, Thomas, Pesch, Beate, Rabstein, Sylvia, Spickenheuer, Anne, Aittomäki, Kristiina, Dörk, Thilo, Margolin, Sara, Mannermaa, Arto, Lambrechts, Diether, Chang-Claude, Jenny, Radice, Paolo, Giles, Graham G., Haiman, Christopher A., Winqvist, Robert, Devillee, Peter, García-Closas, Montserrat, Schoof, Nils, Hooning, M. J., Cox, Angela, Pharoah, Paul D.P., Jakubowska, Anna, Orr, Nick, González-Neira, Anna, Pita, Guillermo, Alonso, M. Rosario, Hall, Per, Couch, Fergus J., Simard, Jacques, Altshuler, David, Easton, Douglas F., Chenevix-Trench, Georgia, Antoniou, Antonis C., Offit, Kenneth, Rookus, M. A., van Leeuwen, F. E., Verhoef, S., de Lange, J. L., Collée, J. M., Seynaeve, C., van Deurzen, C. H.M., van Asperen, C. J., Tollenaar, R. A., Devilee, P., van Cronenburg, T. C.T.E.F., Mensenkamp, A. R., van der Luijt, R. B., van Os, T. A.M., Gille, J. J.P., Waisfisz, Q., Meijers-Heijboer, H. E.J., Gómez-Garcia, E. B., Blok, M. J., Oosterwijk, J. C., Mourits, M. J., de Bock, G. H., Vasen, H. F., Miedzybrodzka, Zosia, Gregory, Helen, Morrison, Patrick, Jeffers, Lisa, Cole, Trevor, Ong, Kai ren, Hoffman, Jonathan, Donaldson, Alan, James, Margaret, Paterson, Joan, Taylor, Amy, Murray, Alexandra, Rogers, Mark T., McCann, Emma, Kennedy, M. John, Barton, David, Drummond, Sarah, Brewer, Carole, Kivuva, Emma, Searle, Anne, Goodman, Selina, Hill, Kathryn, Davidson, Rosemarie, Murday, Victoria, Bradshaw, Nicola, Snadden, Lesley, Longmuir, Mark, Watt, Catherine, Gibson, Sarah, Haque, Eshika, Tobias, Ed, Duncan, Alexis, Izatt, Louise, Langman, Caroline, Brady, Angela, Dorkins, Huw, Melville, Athalie, Randhawa, Kashmir, Barwell, Julian, Serra-Feliu, Gemma, Ellis, Ian, Houghton, Catherine, Lalloo, Fiona, Taylor, Jane, Side, Lucy, Male, Alison, Berlin, Cheryl, Eason, Jacqueline, Douglas, Fiona, Claber, Oonagh, Collier, Rebecca, Jobson, Irene, Walker, Lisa, McLeod, Diane, Durell, Sarah, Stayner, Barbara, Eeles, Rosalind A., Shanley, Susan, Rahman, Nazneen, Houlston, Richard, Bancroft, Elizabeth, Page, Elizabeth, Ardern-Jones, Audrey, Kohut, Kelly, Wiggins, Jennifer, Castro, Elena, Killick, Emma, Martin, Sue, Rea, Gillian, Kulkarni, Anjana, Cook, Jackie, Quarrell, Oliver, Bardsley, Cathryn, Hodgson, Shirley, Goff, Sheila, Brice, Glen, Winchester, Lizzie, Eddy, Charlotte, Tripathi, Vishakha, Attard, Virginia, Lehmann, Anna, Eccles, Diana, Lucassen, Anneke, Crawford, Gillian, McBride, Donna, Smalley, Sarah, Sinilnikova, Olga, Verny-Pierre, Carole, Giraud, Sophie, Léone, Mélanie, Gauthier-Villars, Marion, Buecher, Bruno, Houdayer, Claude, Moncoutier, Virginie, Tirapo, Carole, de Pauw, Antoine, Bressac-de-Paillerets, Brigitte, Caron, Olivier, Bignon, Yves Jean, Uhrhammer, Nancy, Lasset, Christine, Bonadona, Valérie, Handallou, Sandrine, Hardouin, Agnés, Berthet, Pascaline, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Coupier, Isabelle, Pujol, Pascal, Peyrat, Jean Philippe, Fournier, Joëlle, Révillion, Françoise, Vennin, Philippe, Adenis, Claude, Rouleau, Etienne, Lidereau, Rosette, Demange, Liliane, Nogues, Catherine, Muller, Danièle, Fricker, Jean Pierre, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Dreyfus, Hélène, Rebischung, Christine, Peysselon, Magalie, Coron, Fanny, Faivre, Laurence, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Frénay, Marc, Vénat-Bouvet, Laurence, Delnatte, Capucine, Mortemousque, Isabelle, Lynch, Henry T., Snyder, Carrie L., Clinical Genetics, Medical Oncology, Human Genetics, Human genetics, EMGO - Quality of care, Anesthesiology, CCA - Oncogenesis, CCA - Cancer biology and immunology, Epidemiology and Data Science, Department of Obstetrics and Gynecology, Clinicum, and Department of Medical and Clinical Genetics

Subjects
Cancer Research, SUSCEPTIBILITY ALLELES, Genome-wide association study, Aetiology, screening and detection [ONCOL 5], QH426-470, Settore MED/03 - GENETICA MEDICA, Genoma humà, SUBTYPES, Breast cancer, 0302 clinical medicine, Risk Factors, CDKN2A, Genotype, BRCA2 MUTATION CARRIERS, Malalties hereditàries, GWAS, skin and connective tissue diseases, Genetics (clinical), POPULATION, 2. Zero hunger, Genetics, 0303 health sciences, education.field_of_study, BRCA1 Protein, COMMON VARIANTS, genetic modifiers, BRCA2, cancer risk, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 6, Female, Genetic diseases, Adult, Heterozygote, Medizinische Fakultät -ohne weitere Spezifikation, education, Population, Breast Neoplasms, Single-nucleotide polymorphism, Locus (genetics), Human chromosomes, Biology, Polymorphism, Single Nucleotide, OVARIAN-CANCER, BRCA2-specific modifier locus at 6p24, Càncer de mama, 03 medical and health sciences, TRANSCRIPTION FACTOR AP-2, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Allele, GENOME-WIDE ASSOCIATION, Molecular Biology, Alleles, Ecology, Evolution, Behavior and Systematics, Aged, 030304 developmental biology, BRCA2 Protein, Cromosomes humans, Human genome, Hereditary cancer and cancer-related syndromes [ONCOL 1], CONSORTIUM, medicine.disease, Mutation, 3111 Biomedicine, ZNF365, Genome-Wide Association Study
Abstract

Contains fulltext : 118578.pdf (Publisher’s version ) (Open Access) Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9x10(-8)). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer.

Published
2013

34. Counselling in the era of the human genome.

Author

Phillips, Alan, Tripathi, Vishakha, and Tomlinson, Charlotte

Subjects
*HUNTINGTON'S chorea diagnosis, *GENETIC counseling, *PATIENT-professional relations, *GENOMICS, *PATIENTS' attitudes, *PSYCHOLOGY
Abstract

The article focuses on the challenges being raised by genomic medicines for counsellors and clients. It offers information on the Human Genome Project which is the largest collaborative, scientific research project. It mentions that the project is focused on identifying genes of the human genome. It mentions that human genome have all the genetic information, with DNA, and encodes.

Published
2016

35. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Author

Barnes, Daniel R, Silvestri, Valentina, Leslie, Goska, McGuffog, Lesley, Dennis, Joe, Yang, Xin, Adlard, Julian, Agnarsson, Bjarni A, Ahmed, Munaza, Aittomäki, Kristiina, Andrulis, Irene L, Arason, Adalgeir, Arnold, Norbert, Auber, Bernd, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barrowdale, Daniel, Barwell, Julian, Belotti, Muriel, Benitez, Javier, Berthet, Pascaline, Boonen, Susanne E, Borg, Åke, Bozsik, Aniko, Brady, Angela F, Brennan, Paul, Brewer, Carole, Brunet, Joan, Bucalo, Agostino, Buys, Saundra S, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Cassingham, Hayley, Christensen, Lise Lotte, Cini, Giulia, Claes, Kathleen BM, GEMO Study Collaborators, EMBRACE Collaborators, Cook, Jackie, Coppa, Anna, Cortesi, Laura, Damante, Giuseppe, Darder, Esther, Davidson, Rosemarie, De La Hoya, Miguel, De Leeneer, Kim, De Putter, Robin, Del Valle, Jesús, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M, Donaldson, Alan, Eason, Jacqueline, Eeles, Ros, Engel, Christoph, Evans, D Gareth, Feliubadaló, Lidia, Fostira, Florentia, Frone, Megan, Frost, Debra, Gallagher, David, Gehrig, Andrea, Giraud, Sophie, Glendon, Gord, Godwin, Andrew K, Goldgar, David E, Greene, Mark H, Gregory, Helen, Gross, Eva, Hahnen, Eric, Hamann, Ute, Hansen, Thomas VO, Hanson, Helen, Hentschel, Julia, Horvath, Judit, KConFab Investigators, HEBON Investigators, Izatt, Louise, Izquierdo, Angel, James, Paul A, Janavicius, Ramunas, Jensen, Uffe Birk, Johannsson, Oskar Th, John, Esther M, Kramer, Gero, Kroeldrup, Lone, Kruse, Torben A, Lautrup, Charlotte, Lazaro, Conxi, Lesueur, Fabienne, Lopez-Fernández, Adria, Mai, Phuong L, Manoukian, Siranoush, Matrai, Zoltan, Matricardi, Laura, Maxwell, Kara N, Mebirouk, Noura, Meindl, Alfons, Montagna, Marco, Monteiro, Alvaro N, Morrison, Patrick J, Muranen, Taru A, Murray, Alex, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nguyen-Dumont, Tu, Niederacher, Dieter, Olah, Edith, Olopade, Olufunmilayo I, Palli, Domenico, Parsons, Michael T, Pedersen, Inge Sokilde, Peissel, Bernard, Perez-Segura, Pedro, Peterlongo, Paolo, Petersen, Annabeth H, Pinto, Pedro, Porteous, Mary E, Pottinger, Caroline, Pujana, Miquel Angel, Radice, Paolo, Ramser, Juliane, Rantala, Johanna, Robson, Mark, Rogers, Mark T, Rønlund, Karina, Rump, Andreas, Sánchez De Abajo, Ana María, Shah, Payal D, Sharif, Saba, Side, Lucy E, Singer, Christian F, Stadler, Zsofia, Steele, Linda, Stoppa-Lyonnet, Dominique, Sutter, Christian, Tan, Yen Yen, Teixeira, Manuel R, Teulé, Alex, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tommasi, Stefania, Toss, Angela, Trainer, Alison H, Tripathi, Vishakha, Valentini, Virginia, Van Asperen, Christi J, Venturelli, Marta, Viel, Alessandra, Vijai, Joseph, Walker, Lisa, Wang-Gohrke, Shan, Wappenschmidt, Barbara, Whaite, Anna, Zanna, Ines, Offit, Kenneth, Thomassen, Mads, Couch, Fergus J, Schmutzler, Rita K, Simard, Jacques, Easton, Douglas F, Chenevix-Trench, Georgia, Antoniou, Antonis C, Ottini, Laura, and Consortium Of Investigators Of Modifiers Of BRCA1 And BRCA2

Subjects
Aged, 80 and over, BRCA2 Protein, Male, Heterozygote, BRCA1 Protein, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, Risk Assessment, 3. Good health, Risk Factors, Mutation, Humans, Genetic Predisposition to Disease, skin and connective tissue diseases
Abstract

BACKGROUND: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. METHODS: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. RESULTS: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. CONCLUSIONS: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.

36. The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2

Author

Philpott, Sue, Raikou, Maria, Manchanda, Ranjit, Lockley, Michelle, Singh, Naveena, Scott, Malcolm, Evans, D. Gareth, Adlard, Julian, Ahmed, Munaza, Edmondson, Richard, Woodward, Emma Roisin, Lamnisos, Athena, Balega, Janos, Brady, Angela F., Sharma, Aarti, Izatt, Louise, Kulkarni, Anjana, Tripathi, Vishakha, Solomons, Joyce S., Hayes, Kevin, Hanson, Helen, Snape, Katie, Side, Lucy, Skates, Steve, McGuire, Alistair, Rosenthal, Adam N., Philpott, Sue, Raikou, Maria, Manchanda, Ranjit, Lockley, Michelle, Singh, Naveena, Scott, Malcolm, Evans, D. Gareth, Adlard, Julian, Ahmed, Munaza, Edmondson, Richard, Woodward, Emma Roisin, Lamnisos, Athena, Balega, Janos, Brady, Angela F., Sharma, Aarti, Izatt, Louise, Kulkarni, Anjana, Tripathi, Vishakha, Solomons, Joyce S., Hayes, Kevin, Hanson, Helen, Snape, Katie, Side, Lucy, Skates, Steve, McGuire, Alistair, and Rosenthal, Adam N.

Abstract

BACKGROUND: Our study aimed to establish 'real-world' performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). METHODS: Our study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. RESULTS: Our study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9-100), 75% (34.9-96.8) and 99.9% (99.9-100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost -saving of -£102,496/QALY. CONCLUSION: OC surveillance for women deferring RRSO in a 'real-world' setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.

37. THE TYRANNY OF SILENCE: GIVING SORROW WORDS IN THE CONTEXT OF GENETIC COUNSELLING.

Author

PHILLIPS, ALAN, TRIPATHI, VISHAKHA, and TOMLINSON, CHARLOTTE

Subjects
*GENETIC disorder diagnosis, *HUNTINGTON disease, *HUNTINGTON'S chorea diagnosis, *COUNSELORS, *DECISION making, *GENETIC counseling, *GRIEF, *HUMAN genome, *NATIONAL health services, *CLIENT relations, *GENETICS
Abstract

The article explores genetic counselling, a strand of counselling that helps people who are considering undergoing genetic testing for inheritable diseases. Topics include how genetic and therapeutic counsellors can work together to help clients make difficult decisions. Also mentioned are loss and grief being inherent in decision making process within genetic counselling, with the stress and responsibility of the predictive testing process tapping into unresolved psychological issues.

Published
2016

38. Validation of the BOADICEA model in a prospective cohort of BRCA1/2 pathogenic variant carriers.

Author

Yang X, Mooij TM, Leslie G, Ficorella L, Andrieu N, Kast K, Singer CF, Jakubowska A, van Gils CH, Tan YY, Engel C, Adank MA, van Asperen CJ, Ausems MGEM, Berthet P, Collee MJ, Cook JA, Eason J, Spaendonck-Zwarts KYV, Evans DG, Gómez García EB, Hanson H, Izatt L, Kemp Z, Lalloo F, Lasset C, Lesueur F, Musgrave H, Nambot S, Noguès C, Oosterwijk JC, Stoppa-Lyonnet D, Tischkowitz M, Tripathi V, Wevers MR, Zhao E, van Leeuwen FE, Schmidt MK, Easton DF, Rookus MA, and Antoniou AC

Subjects
Humans, Female, Middle Aged, Adult, Prospective Studies, Risk Factors, Risk Assessment, Polymorphism, Single Nucleotide genetics, Breast Neoplasms genetics, Breast Neoplasms epidemiology, BRCA2 Protein genetics, BRCA1 Protein genetics, Heterozygote, Genetic Predisposition to Disease
Abstract

Background: No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in BRCA1/2 pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of BRCA1/2 PV carriers ascertained through clinical genetic centres., Methods: We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 BRCA1 and 1365 BRCA2 PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information., Results: The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell's C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in BRCA1 or BRCA2 PV carriers. The full model identified 5.8%, 12.9% and 24.0% of BRCA1/2 PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options., Conclusion: BOADICEA may be used to aid personalised cancer risk management and decision-making for BRCA1 and BRCA2 PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/)., Competing Interests: Competing interests: ACA and DFE are named creators of the BOADICEA model which has been licensed by Cambridge Enterprise (University of Cambridge). All the other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Published
2024
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39. Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores.

Author

Barnes DR, Silvestri V, Leslie G, McGuffog L, Dennis J, Yang X, Adlard J, Agnarsson BA, Ahmed M, Aittomäki K, Andrulis IL, Arason A, Arnold N, Auber B, Azzollini J, Balmaña J, Barkardottir RB, Barrowdale D, Barwell J, Belotti M, Benitez J, Berthet P, Boonen SE, Borg Å, Bozsik A, Brady AF, Brennan P, Brewer C, Brunet J, Bucalo A, Buys SS, Caldés T, Caligo MA, Campbell I, Cassingham H, Christensen LL, Cini G, Claes KBM, Cook J, Coppa A, Cortesi L, Damante G, Darder E, Davidson R, de la Hoya M, De Leeneer K, de Putter R, Del Valle J, Diez O, Ding YC, Domchek SM, Donaldson A, Eason J, Eeles R, Engel C, Evans DG, Feliubadaló L, Fostira F, Frone M, Frost D, Gallagher D, Gehrig A, Giraud S, Glendon G, Godwin AK, Goldgar DE, Greene MH, Gregory H, Gross E, Hahnen E, Hamann U, Hansen TVO, Hanson H, Hentschel J, Horvath J, Izatt L, Izquierdo A, James PA, Janavicius R, Jensen UB, Johannsson OT, John EM, Kramer G, Kroeldrup L, Kruse TA, Lautrup C, Lazaro C, Lesueur F, Lopez-Fernández A, Mai PL, Manoukian S, Matrai Z, Matricardi L, Maxwell KN, Mebirouk N, Meindl A, Montagna M, Monteiro AN, Morrison PJ, Muranen TA, Murray A, Nathanson KL, Neuhausen SL, Nevanlinna H, Nguyen-Dumont T, Niederacher D, Olah E, Olopade OI, Palli D, Parsons MT, Pedersen IS, Peissel B, Perez-Segura P, Peterlongo P, Petersen AH, Pinto P, Porteous ME, Pottinger C, Pujana MA, Radice P, Ramser J, Rantala J, Robson M, Rogers MT, Rønlund K, Rump A, Sánchez de Abajo AM, Shah PD, Sharif S, Side LE, Singer CF, Stadler Z, Steele L, Stoppa-Lyonnet D, Sutter C, Tan YY, Teixeira MR, Teulé A, Thull DL, Tischkowitz M, Toland AE, Tommasi S, Toss A, Trainer AH, Tripathi V, Valentini V, van Asperen CJ, Venturelli M, Viel A, Vijai J, Walker L, Wang-Gohrke S, Wappenschmidt B, Whaite A, Zanna I, Offit K, Thomassen M, Couch FJ, Schmutzler RK, Simard J, Easton DF, Chenevix-Trench G, Antoniou AC, and Ottini L

Subjects
Aged, 80 and over, BRCA1 Protein genetics, BRCA2 Protein genetics, Genetic Predisposition to Disease, Heterozygote, Humans, Male, Mutation, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Prostatic Neoplasms epidemiology, Prostatic Neoplasms genetics
Abstract

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers., Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk., Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions., Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management., (© The Author(s) 2021. Published by Oxford University Press.)

Published
2022
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40. Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers.

Author

Page EC, Bancroft EK, Brook MN, Assel M, Hassan Al Battat M, Thomas S, Taylor N, Chamberlain A, Pope J, Raghallaigh HN, Evans DG, Rothwell J, Maehle L, Grindedal EM, James P, Mascarenhas L, McKinley J, Side L, Thomas T, van Asperen C, Vasen H, Kiemeney LA, Ringelberg J, Jensen TD, Osther PJS, Helfand BT, Genova E, Oldenburg RA, Cybulski C, Wokolorczyk D, Ong KR, Huber C, Lam J, Taylor L, Salinas M, Feliubadaló L, Oosterwijk JC, van Zelst-Stams W, Cook J, Rosario DJ, Domchek S, Powers J, Buys S, O'Toole K, Ausems MGEM, Schmutzler RK, Rhiem K, Izatt L, Tripathi V, Teixeira MR, Cardoso M, Foulkes WD, Aprikian A, van Randeraad H, Davidson R, Longmuir M, Ruijs MWG, Helderman van den Enden ATJM, Adank M, Williams R, Andrews L, Murphy DG, Halliday D, Walker L, Liljegren A, Carlsson S, Azzabi A, Jobson I, Morton C, Shackleton K, Snape K, Hanson H, Harris M, Tischkowitz M, Taylor A, Kirk J, Susman R, Chen-Shtoyerman R, Spigelman A, Pachter N, Ahmed M, Ramon Y Cajal T, Zgajnar J, Brewer C, Gadea N, Brady AF, van Os T, Gallagher D, Johannsson O, Donaldson A, Barwell J, Nicolai N, Friedman E, Obeid E, Greenhalgh L, Murthy V, Copakova L, Saya S, McGrath J, Cooke P, Rønlund K, Richardson K, Henderson A, Teo SH, Arun B, Kast K, Dias A, Aaronson NK, Ardern-Jones A, Bangma CH, Castro E, Dearnaley D, Eccles DM, Tricker K, Eyfjord J, Falconer A, Foster C, Gronberg H, Hamdy FC, Stefansdottir V, Khoo V, Lindeman GJ, Lubinski J, Axcrona K, Mikropoulos C, Mitra A, Moynihan C, Rennert G, Suri M, Wilson P, Dudderidge T, Offman J, Kote-Jarai Z, Vickers A, Lilja H, and Eeles RA

Subjects
Adult, Aged, Humans, Kallikreins blood, Male, Middle Aged, Prospective Studies, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Early Detection of Cancer methods, Genes, BRCA1, Genes, BRCA2, Genetic Carrier Screening methods, Germ-Line Mutation, Prostatic Neoplasms diagnosis, Prostatic Neoplasms genetics
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 biopsy than PSA alone (AUC = 0.65)., Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers., Patient Summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2019
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