Author: "Ausems, M.G.E.M. (Margreet)" - Searchworks@Jio Institute Digital Library Search Results

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1. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, J. (Juliette), Lush, M. (Michael), Beesley, J. (Jonathan), O’Mara, T.A. (Tracy A.), Dennis, J. (Joe), Tyrer, J.P. (Jonathan P.), Barnes, D. (Daniel), McGuffog, L. (Lesley), Leslie, G. (Goska), Bolla, M.K. (Manjeet K.), Adank, M.A. (Muriel), Agata, S. (Simona), Ahearn, T. (Thomas), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Augustinsson, A. (Annelie), Azzollini, J., Barrowdale, D. (Daniel), Baynes, C. (Caroline), Becher, H. (Heko), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Białkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campa, D. (Daniele), Carter, B.D. (Brian D.), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B. M.), Clarke, C.L. (Christine L.), Bertrand, O. (Ophélie), Caputo, S. (Sandrine), Dupré, A. (Anaïs), Le Mentec, M. (Marine), Belotti, M. (Muriel), Birot, A.-M. (Anne-Marie), Buecher, B. (Bruno), Fourme, E. (Emmanuelle), Gauthier-Villars, M. (Marion), Golmard, L. (Lisa), Houdayer, C. (Claude), Moncoutier, V. (Virginie), de Pauw, A. (Antoine), Saule, C. (Claire), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Bressac-de Paillerets, B. (Brigitte), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Noguchi, T. (Tetsuro), Popovici, C. (Cornel), Sobol, H. (Hagay), Bourdon, V. (Violaine), Remenieras, A. (Audrey), Nogues, C. (Catherine), Coupier, I. (Isabelle), Pujol, P. (Pascal), Dumont, A. (Aurélie), Révillion, F. (Françoise), Adenis, C. (Claude), Muller, D.W. (Danièle), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Mari, V. (Véronique), Vénat-Bouvet, L. (Laurence), Delnatte, C. (Capucine), Bézieau, S. (Stéphane), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F. (Florent), Warcoin, M. (Mathilde), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Collonge-Rame, M.-A., Damette, A. (Alexandre), Gesta, P. (Paul), Lallaoui, H. (Hakima), Chiesa, J. (Jean), Molina-Gomes, D. (Denise), Ingster, O. (Olivier), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick J.), Ong, K.-R. (Kai-ren), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (M. John), Porteous, M.E. (Mary), Brewer, C. (Carole), Davidson, R. (Rosemarie), Izatt, L. (Louise), Brady, A. (A.), Barwell, J. (Julian), Adlard, J.W. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L.E. (Lucy E.), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L. (Lisa), Eeles, R. (Rosalind), Cook, J. (Jackie), Snape, K. (Katie), Eccles, D. (Diana), Murray, A. (Alexandra), McCann, E. (Emma), Collée, J.M. (J. Margriet), Conroy, D.M. (Don M.), Czene, K. (Kamila), Daly, M.B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Ding, Y.C. (Yuan Chun), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Garcia-Barberan, V. (Vanesa), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Gayther, S.A. (Simon), Gehrig, A. (Andrea), Georgoulias, V. (Vassilios), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), He, W. (Wei), Hogervorst, F.B.L. (Frans B. L.), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Horcasitas, D.J. (Darling J.), Hulick, P.J. (Peter J.), Hunter, D.J. (David J.), Imyanitov, E.N. (Evgeny), Fox, S.B. (Stephen), Campbell, I. (Ian), Spurdle, A. (Amanda), Webb, P. (Penny), De Fazio, A. (Anna), Tassell, M. (Margaret), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Southey, M.C. (Melissa), Milne, R.L. (Roger), Deb, S. (Sid), Bowtell, D. (David), Hout, A.H. (Annemarie) van der, Ouweland, A.M.W. (Ans) van den, Mensenkamp, A.R. (Arjen R.), Deurzen, C.H.M. (Carolien) van, Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), van Asperen, C.J. (Christi J.), Aalfs, C.M. (Cora), Gómez Garcia, E.B. (Encarna B.), Leeuwen, F.E. (Flora) van, Bock, G.H. (Geertruida) de, Meijers-Heijboer, E.J. (Hanne), Obdeijn, A.I.M. (Inge-Marie), Gille, J.J.P. (J. J.P.), Oosterwijk, J.C. (Jan), Wijnen, J.T. (Juul), Kolk, L.E. (Lizet) van der, Hooning, M.J. (Maartje), Ausems, M.G.E.M. (Margreet), Mourits, M.J. (Marjan), Blok, M.J. (Marinus J.), Rookus, M.A. (Matti), van der Luijt, R.B. (Rob B.), Cronenburg, T.C.T.E.F. van, Pol, C. (Carmen) van der, Russell, N.S. (Nicola), Siesling, S. (Sabine), Overbeek, L.I.H. (Lucy), Wijnands, R. (R.), Lange, J.L. (J.) de, Clarke, C. (Christine), Graham, D. (Dinny), Sachchithananthan, M. (Mythily), Marsh, D. (Deborah), Scott, R.J. (Rodney), Baxter, R. (Robert), Yip, D. (Desmond), Carpenter, T.A. (Adrian), Davis, A. (Alison), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Jager, A. (Agnes), Jakubowska, A. (Anna), James, M. (Margaret), Jensen, U.B. (Uffe Birk), John, E.M. (Esther), Jones, M.E. (Michael E.), Kaaks, R. (Rudolf), Kapoor, P.M. (Pooja Middha), Karlan, B.Y. (Beth), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kurian, A.W. (Allison W.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, T. (Tricia), Lopez-Fernández, A. (Adria), Loud, J.T. (Jennifer T.), Luccarini, C. (Craig), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Mebirouk, N. (Noura), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger L.), Montagna, M. (Marco), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nielsen, F.C. (Finn C.), O’Brien, K.M. (Katie M.), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Osorio, A. (Ana), Ottini, L. (Laura), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge Sokilde), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Polley, E.C. (Eric C.), Poppe, B. (Bruce), Presneau, N. (Nadege), Pujana, M.A. (Miquel Angel), Punie, K. (Kevin), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Robson, M. (Mark), Romero, A. (Atocha), Rossing, M. (Maria), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santella, R.M. (Regina), Scheuner, M.T. (Maren T.), Schmidt, M.K. (Marjanka K.), Schmidt, G. (Gunnar), Scott, C. (Christopher), Sharma, P. (Priyanka), Soucy, P. (Penny), Southey, M.C. (Melissa C.), Spinelli, J.J. (John J.), Steinsnyder, Z. (Zoe), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Trainer, A.H. (Alison H.), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), Vega, A. (Ana), Joseph, V. (Vijai), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Wolk, K. (Kerstin), Yadav, S. (Siddhartha), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Park, S.K. (Sue K.), Thomassen, M. (Mads), Offit, K. (Kenneth), Schmutzler, R.K. (Rita), Couch, F.J. (Fergus), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Adamo, P. (Pio) d', Andrieu, N. (Nadine), Antoniou, A.C. (Antonis C.), Coignard, J. (Juliette), Lush, M. (Michael), Beesley, J. (Jonathan), O’Mara, T.A. (Tracy A.), Dennis, J. (Joe), Tyrer, J.P. (Jonathan P.), Barnes, D. (Daniel), McGuffog, L. (Lesley), Leslie, G. (Goska), Bolla, M.K. (Manjeet K.), Adank, M.A. (Muriel), Agata, S. (Simona), Ahearn, T. (Thomas), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene L.), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arnold, N. (Norbert), Aronson, K.J. (Kristan J.), Arun, B.K. (Banu), Augustinsson, A. (Annelie), Azzollini, J., Barrowdale, D. (Daniel), Baynes, C. (Caroline), Becher, H. (Heko), Bermisheva, M. (Marina), Bernstein, L. (Leslie), Białkowska, K. (Katarzyna), Blomqvist, C. (Carl), Bojesen, S.E. (Stig), Bonnani, B. (Bernardo), Borg, Å. (Åke), Brauch, H. (Hiltrud), Brenner, H. (Hermann), Burwinkel, B. (Barbara), Buys, S.S. (Saundra S.), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campa, D. (Daniele), Carter, B.D. (Brian D.), Castelao, J.E. (Jose ), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen J.), Chung, W.K. (Wendy K.), Claes, K.B.M. (Kathleen B. M.), Clarke, C.L. (Christine L.), Bertrand, O. (Ophélie), Caputo, S. (Sandrine), Dupré, A. (Anaïs), Le Mentec, M. (Marine), Belotti, M. (Muriel), Birot, A.-M. (Anne-Marie), Buecher, B. (Bruno), Fourme, E. (Emmanuelle), Gauthier-Villars, M. (Marion), Golmard, L. (Lisa), Houdayer, C. (Claude), Moncoutier, V. (Virginie), de Pauw, A. (Antoine), Saule, C. (Claire), Sinilnikova, O. (Olga), Mazoyer, S. (Sylvie), Damiola, F. (Francesca), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Bressac-de Paillerets, B. (Brigitte), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Noguchi, T. (Tetsuro), Popovici, C. (Cornel), Sobol, H. (Hagay), Bourdon, V. (Violaine), Remenieras, A. (Audrey), Nogues, C. (Catherine), Coupier, I. (Isabelle), Pujol, P. (Pascal), Dumont, A. (Aurélie), Révillion, F. (Françoise), Adenis, C. (Claude), Muller, D.W. (Danièle), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Mari, V. (Véronique), Vénat-Bouvet, L. (Laurence), Delnatte, C. (Capucine), Bézieau, S. (Stéphane), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F. (Florent), Warcoin, M. (Mathilde), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Collonge-Rame, M.-A., Damette, A. (Alexandre), Gesta, P. (Paul), Lallaoui, H. (Hakima), Chiesa, J. (Jean), Molina-Gomes, D. (Denise), Ingster, O. (Olivier), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick J.), Ong, K.-R. (Kai-ren), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (M. John), Porteous, M.E. (Mary), Brewer, C. (Carole), Davidson, R. (Rosemarie), Izatt, L. (Louise), Brady, A. (A.), Barwell, J. (Julian), Adlard, J.W. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L.E. (Lucy E.), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L. (Lisa), Eeles, R. (Rosalind), Cook, J. (Jackie), Snape, K. (Katie), Eccles, D. (Diana), Murray, A. (Alexandra), McCann, E. (Emma), Collée, J.M. (J. Margriet), Conroy, D.M. (Don M.), Czene, K. (Kamila), Daly, M.B. (Mary B.), Devilee, P. (Peter), Diez, O. (Orland), Ding, Y.C. (Yuan Chun), Domchek, S.M. (Susan), Dörk, T. (Thilo), Santos Silva, I. (Isabel) dos, Dunning, A.M. (Alison M.), Dwek, M. (Miriam), Eccles, D.M. (Diana M.), Eliassen, A.H. (A. Heather), Engel, C. (Christoph), Eriksson, M. (Mikael), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Flyger, H. (Henrik), Fostira, F. (Florentia), Friedman, E. (Eitan), Fritschi, L. (Lin), Frost, D. (Debra), Gago-Dominguez, M. (Manuela), Gapstur, S.M. (Susan M.), Garber, J. (Judy), Garcia-Barberan, V. (Vanesa), García-Closas, M. (Montserrat), García-Sáenz, J.A. (José A.), Gaudet, M.M. (Mia M.), Gayther, S.A. (Simon), Gehrig, A. (Andrea), Georgoulias, V. (Vassilios), Giles, G.G. (Graham G.), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Radice, P. (Paolo), González-Neira, A. (Anna), Greene, M.H. (Mark H.), Guénel, P. (Pascal), Haeberle, L. (Lothar), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hall, P. (Per), Hamann, U. (Ute), Harrington, P.A. (Patricia A.), Hart, S.N. (Steven N.), He, W. (Wei), Hogervorst, F.B.L. (Frans B. L.), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Horcasitas, D.J. (Darling J.), Hulick, P.J. (Peter J.), Hunter, D.J. (David J.), Imyanitov, E.N. (Evgeny), Fox, S.B. (Stephen), Campbell, I. (Ian), Spurdle, A. (Amanda), Webb, P. (Penny), De Fazio, A. (Anna), Tassell, M. (Margaret), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Southey, M.C. (Melissa), Milne, R.L. (Roger), Deb, S. (Sid), Bowtell, D. (David), Hout, A.H. (Annemarie) van der, Ouweland, A.M.W. (Ans) van den, Mensenkamp, A.R. (Arjen R.), Deurzen, C.H.M. (Carolien) van, Kets, C.M. (Marleen), Seynaeve, C.M. (Caroline), van Asperen, C.J. (Christi J.), Aalfs, C.M. (Cora), Gómez Garcia, E.B. (Encarna B.), Leeuwen, F.E. (Flora) van, Bock, G.H. (Geertruida) de, Meijers-Heijboer, E.J. (Hanne), Obdeijn, A.I.M. (Inge-Marie), Gille, J.J.P. (J. J.P.), Oosterwijk, J.C. (Jan), Wijnen, J.T. (Juul), Kolk, L.E. (Lizet) van der, Hooning, M.J. (Maartje), Ausems, M.G.E.M. (Margreet), Mourits, M.J. (Marjan), Blok, M.J. (Marinus J.), Rookus, M.A. (Matti), van der Luijt, R.B. (Rob B.), Cronenburg, T.C.T.E.F. van, Pol, C. (Carmen) van der, Russell, N.S. (Nicola), Siesling, S. (Sabine), Overbeek, L.I.H. (Lucy), Wijnands, R. (R.), Lange, J.L. (J.) de, Clarke, C. (Christine), Graham, D. (Dinny), Sachchithananthan, M. (Mythily), Marsh, D. (Deborah), Scott, R.J. (Rodney), Baxter, R. (Robert), Yip, D. (Desmond), Carpenter, T.A. (Adrian), Davis, A. (Alison), Pathmanathan, N. (Nirmala), Simpson, P. (Peter), Jager, A. (Agnes), Jakubowska, A. (Anna), James, M. (Margaret), Jensen, U.B. (Uffe Birk), John, E.M. (Esther), Jones, M.E. (Michael E.), Kaaks, R. (Rudolf), Kapoor, P.M. (Pooja Middha), Karlan, B.Y. (Beth), Keeman, R. (Renske), Khusnutdinova, E.K. (Elza), Kiiski, J.I. (Johanna I.), Ko, Y.-D. (Yon-Dschun), Kosma, V.-M. (Veli-Matti), Kraft, P. (Peter), Kurian, A.W. (Allison W.), Laitman, Y. (Yael), Lambrechts, D. (Diether), Le Marchand, L. (Loic), Lester, J. (Jenny), Lesueur, F. (Fabienne), Lindstrom, T. (Tricia), Lopez-Fernández, A. (Adria), Loud, J.T. (Jennifer T.), Luccarini, C. (Craig), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Margolin, S. (Sara), Martens, J.W.M. (John), Mebirouk, N. (Noura), Meindl, A. (Alfons), Miller, A. (Austin), Milne, R.L. (Roger L.), Montagna, M. (Marco), Nathanson, K.L. (Katherine), Floris, O.A.M., Nevanlinna, H. (Heli), Nielsen, F.C. (Finn C.), O’Brien, K.M. (Katie M.), Olopade, O.I. (Olofunmilayo), Olson, J.E. (Janet), Olsson, H. (Håkan), Osorio, A. (Ana), Ottini, L. (Laura), Park-Simon, T.-W. (Tjoung-Won), Parsons, M. (Marilyn), Pedersen, I.S. (Inge Sokilde), Peshkin, B. (Beth), Peterlongo, P. (Paolo), Peto, J. (Julian), Pharoah, P.D.P. (Paul), Phillips, K.-A. (Kelly-Anne), Polley, E.C. (Eric C.), Poppe, B. (Bruce), Presneau, N. (Nadege), Pujana, M.A. (Miquel Angel), Punie, K. (Kevin), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rennert, H.S. (Hedy S.), Robson, M. (Mark), Romero, A. (Atocha), Rossing, M. (Maria), Saloustros, E. (Emmanouil), Sandler, D.P. (Dale P.), Santella, R.M. (Regina), Scheuner, M.T. (Maren T.), Schmidt, M.K. (Marjanka K.), Schmidt, G. (Gunnar), Scott, C. (Christopher), Sharma, P. (Priyanka), Soucy, P. (Penny), Southey, M.C. (Melissa C.), Spinelli, J.J. (John J.), Steinsnyder, Z. (Zoe), Stone, J. (Jennifer), Stoppa-Lyonnet, D. (Dominique), Swerdlow, A.J. (Anthony ), Tamimi, R. (Rulla), Tapper, W.J. (William J.), Taylor, J.A. (Jack A.), Terry, M.B. (Mary Beth), Teulé, A. (Alex), Thull, D.L. (Darcy L.), Tischkowitz, M. (Marc), Toland, A.E. (Amanda), Torres, D. (Diana), Trainer, A.H. (Alison H.), Truong, T. (Thérèse), Tung, N. (Nadine), Vachon, C. (Celine), Vega, A. (Ana), Joseph, V. (Vijai), Wang, Q. (Qin), Wappenschmidt, B. (Barbara), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wendt, C. (Camilla), Wolk, K. (Kerstin), Yadav, S. (Siddhartha), Yang, X.R. (Xiaohong R.), Yannoukakos, D. (Drakoulis), Zheng, W. (Wei), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Park, S.K. (Sue K.), Thomassen, M. (Mads), Offit, K. (Kenneth), Schmutzler, R.K. (Rita), Couch, F.J. (Fergus), Simard, J. (Jacques), Chenevix-Trench, G. (Georgia), Adamo, P. (Pio) d', Andrieu, N. (Nadine), and Antoniou, A.C. (Antonis C.)
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
Published: 2021
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2. Long-term morbidity and health after early menopause due to oophorectomy in women at increased risk of ovarian cancer: Protocol for a nationwide cross-sectional study with prospective follow-up (HARMOny Study)

Author: Terra, L. (Lara), Hooning, M.J. (Maartje), Heemskerk-Gerritsen, B.A.M. (Bernadette A.M.), Beurden, M. (Marc) van, Roeters van Lennep, J.E. (Jeanine), Doorn, H.C. (Lena) van, Hullu, J.A. (Joanne) de, Mom, C.H. (Constantijne), van Dorst, E.B.L. (Eleonora B.L.), Mourits, M.J. (Marjan), Slangen, A.H.L. (Arjen), Gaarenstroom, K.N. (Katja), Zillikens, M.C. (Carola), Leiner, I. (Tim), Kolk, L.E. (Lizet) van der, Collée, J.M. (Margriet), Wevers, M.R., Ausems, M.G.E.M. (Margreet), Engelen, K. (Klaartje) van, Berger, L.P.V. (Lieke P.V.), van Asperen, C.J. (Christi J.), Gomez-Garcia, E.B. (Encarna B.), van de Beek, I. (Irma), Rookus, M.A. (Matti), Hauptmann, M. (Michael), Bleiker, E.M.A. (Eveline), Schagen, S.B. (Sanne), Aaronson, N.K. (Neil), Maas, A.H.E.M. (Angela H.E.M.), Leeuwen, F.E. (Flora) van, Terra, L. (Lara), Hooning, M.J. (Maartje), Heemskerk-Gerritsen, B.A.M. (Bernadette A.M.), Beurden, M. (Marc) van, Roeters van Lennep, J.E. (Jeanine), Doorn, H.C. (Lena) van, Hullu, J.A. (Joanne) de, Mom, C.H. (Constantijne), van Dorst, E.B.L. (Eleonora B.L.), Mourits, M.J. (Marjan), Slangen, A.H.L. (Arjen), Gaarenstroom, K.N. (Katja), Zillikens, M.C. (Carola), Leiner, I. (Tim), Kolk, L.E. (Lizet) van der, Collée, J.M. (Margriet), Wevers, M.R., Ausems, M.G.E.M. (Margreet), Engelen, K. (Klaartje) van, Berger, L.P.V. (Lieke P.V.), van Asperen, C.J. (Christi J.), Gomez-Garcia, E.B. (Encarna B.), van de Beek, I. (Irma), Rookus, M.A. (Matti), Hauptmann, M. (Michael), Bleiker, E.M.A. (Eveline), Schagen, S.B. (Sanne), Aaronson, N.K. (Neil), Maas, A.H.E.M. (Angela H.E.M.), and Leeuwen, F.E. (Flora) van
Abstract: Background: BRCA1/2 mutation carriers are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO) at 35 to 45 years of age. RRSO substantially decreases ovarian cancer risk, but at the cost of immediate menopause. Knowledge about the potential adverse effects of premenopausal RRSO, such as increased risk of cardiovascular disease, osteoporosis, cognitive dysfunction, and reduced health-related quality of life (HRQoL), is limited. Objective: The aim of this study is to assess the long-term health effects of premenopausal RRSO on cardiovascular disease, bone health, cognitive functioning, urological complaints, sexual functioning, and HRQoL in women with high familial risk of breast or ovarian cancer. Methods: We will conduct a multicenter cross-sectional study with prospective follow-up, nested in a nationwide cohort of women at high familial risk of breast or ovarian cancer. A total of 500 women who have undergone RRSO before 45 years of age, with a follow-up period of at least 10 years, will be compared with 250 women (frequency matched on current age) who have not undergone RRSO or who have undergone RRSO at over 55 years of age. Participants will complete an online questionnaire on lifestyle, medical history, cardiovascular risk factors, osteoporosis, cognitive function, urological complaints, and HRQoL. A full cardiovascular assessment and assessment of bone mineral density will be performed. Blood samples will be obtained for marker analysis. Cognitive functioning will be assessed objectively with an online neuropsychological test battery. Results: This study was approved by the institutional review board in July 2018. In February 2019, we included our first participant. As of November 2020, we had enrolled 364 participants in our study. Conclusions: Knowledge from this study will contribute to counseling women with a high familial risk of breast/ovarian cancer about the long-term health effects of premenopausal RRSO. The results can also be used to o
Published: 2021
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3. Reproductive decision-making in the context of hereditary cancer: the effects of an online decision aid on informed decision-making

Author: Reumkens, K. (Kelly), Tummers, M.H.E. (Marly H. E.), Severijns, Y. (Yil), Gietel-Habets, J.J.G. (Joyce J. G.), Kuijk, S.M.J. (Sander) van, Aalfs, C.M. (Cora), van Asperen, C.J. (Christi J.), Ausems, M.G.E.M. (Margreet), Collée, J.M. (Margriet), Dommering, C.J. (Charlotte), Kets, C.M. (Marleen), Kolk, L.E. (Lizet) van der, Oosterwijk, J.C. (Jan), Tjan-Heijnen, V.C.G. (Vivianne), Weijden, T. (Trudy) van der, Die-Smulders, C. (Christine) de, van Osch, L.A.D.M. (Liesbeth A. D. M.), Reumkens, K. (Kelly), Tummers, M.H.E. (Marly H. E.), Severijns, Y. (Yil), Gietel-Habets, J.J.G. (Joyce J. G.), Kuijk, S.M.J. (Sander) van, Aalfs, C.M. (Cora), van Asperen, C.J. (Christi J.), Ausems, M.G.E.M. (Margreet), Collée, J.M. (Margriet), Dommering, C.J. (Charlotte), Kets, C.M. (Marleen), Kolk, L.E. (Lizet) van der, Oosterwijk, J.C. (Jan), Tjan-Heijnen, V.C.G. (Vivianne), Weijden, T. (Trudy) van der, Die-Smulders, C. (Christine) de, and van Osch, L.A.D.M. (Liesbeth A. D. M.)
Abstract: Individuals having a genetic predisposition to cancer and their partners face challenging decisions regarding their wish to have children. This study aimed to determine the effects of an online decision aid to support couples in making an informed decision regarding their reproductive options. A nationwide pretest-posttest study was conducted in the Netherlands among 131 participants between November 2016 and May 2018. Couples were eligible for participation if one partner had a pathogenic variant predisposing for an autosomal dominant hereditary cancer syndrome. Participants completed a questionnaire before use (T0), and at 3 months (T3) after use of the decision aid to assess the primary outcome measure informed decision-making, and the secondary outcome measures decisional conflict, knowledge, realistic expectations, level of deliberation, and decision self-efficacy. T0–T3 comparisons show an overall positive effect for all outcome measures (all ps < 0.05; knowledge (ES = − 1.05), decisional conflict (ES = 0.99), participants’ decision self-efficacy (ES = −0.55), level of deliberation (ES = − 0.50), and realistic expectations (ES = − 0.44). Informed decision-making increased over time and 58.0% of the participants made an informed reproductive decision at T3. The online decision aid seems to be an appropriate tool to complement standard reproductive counseling to support our target group in making an informed reproductive decision. Use of the decision aid may lessen the negative psychological impact of decision-making on couples’ daily life and wellbeing.
Published: 2020
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4. Patient-reported burden of intensified surveillance and surgery in high-risk individuals under pancreatic cancer surveillance

Author: Overbeek, K.A. (Kasper A.), Cahen, D.L. (Djuna), Kamps, A. (Anne), Konings, I.C.A.W. (Ingrid C. A. W.), Harinck, F. (Femme), Kuenen, M.A. (Marianne), Koerkamp, B.G. (Bas Groot), Besselink, M.G. (Marc), Eijck, C.H.J. (Casper) van, Wagner, A. (Anja), Ausems, M.G.E.M. (Margreet), van der Vlugt, M. (Manon), Fockens, P. (Paul), Vleggaar, F.P. (Frank P.), Poley, J.-W. (Jan-Werner), Hooft, J.E. (Jeanin) van, Bleiker, E.M.A. (Eveline M. A.), Bruno, M.J. (Marco J.), Bruno, M.J. (Marco), Cahen, D.L. (D. L.), Poley, J.W. (J. W.), M. Levink, I.J. (I. J.), Koopmann, B. (B.), Biermann, K. (Katharina), Peppelenbosch, M.P. (Maikel), van Hooft, J.E. (J. E.), Vlugt, M.J. (Maureen) van der, Bastiaansen, D. (Dennis), Besselink, M.G. (M. G.), Ausems, M.G.E. (M. G.E.), Velthuizen, M.E. (Mary E.), Vleggaar, F.P. (Frank), Dullemen, H.M. (Hendrik) van, Bleiker, E.M.A. (Eveline), Overbeek, K.A. (Kasper A.), Cahen, D.L. (Djuna), Kamps, A. (Anne), Konings, I.C.A.W. (Ingrid C. A. W.), Harinck, F. (Femme), Kuenen, M.A. (Marianne), Koerkamp, B.G. (Bas Groot), Besselink, M.G. (Marc), Eijck, C.H.J. (Casper) van, Wagner, A. (Anja), Ausems, M.G.E.M. (Margreet), van der Vlugt, M. (Manon), Fockens, P. (Paul), Vleggaar, F.P. (Frank P.), Poley, J.-W. (Jan-Werner), Hooft, J.E. (Jeanin) van, Bleiker, E.M.A. (Eveline M. A.), Bruno, M.J. (Marco J.), Bruno, M.J. (Marco), Cahen, D.L. (D. L.), Poley, J.W. (J. W.), M. Levink, I.J. (I. J.), Koopmann, B. (B.), Biermann, K. (Katharina), Peppelenbosch, M.P. (Maikel), van Hooft, J.E. (J. E.), Vlugt, M.J. (Maureen) van der, Bastiaansen, D. (Dennis), Besselink, M.G. (M. G.), Ausems, M.G.E. (M. G.E.), Velthuizen, M.E. (Mary E.), Vleggaar, F.P. (Frank), Dullemen, H.M. (Hendrik) van, and Bleiker, E.M.A. (Eveline)
Abstract: In high-risk individuals participating in a pancreatic cancer surveillance program, worrisome features warrant for intensified surveillance or, occasionally, surgery. Our objectives were to determine the patient-reported burden of intensified surveillance and/or surgery, and to assess post-operative quality of life and opinion of surgery. Participants in our pancreatic cancer surveillance program completed questionnaires including the Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale (HADS). For individuals who underwent intensified surveillance, questionnaires before, during, and ≥ 3 weeks after were analyzed. In addition, subjects who underwent intensified surveillance in the past 3 years or underwent surgery at any time, were invited for an interview, that included the Short-Form 12 (SF-12). A total of 31 high-risk individuals were studied. During the intensified surveillance period, median CWS scores were higher (14, IQR 7), as compared to before (12, IQR 9, P = 0.007) and after (11, IQR 7, P = 0.014), but eventually returned back to baseline (P = 0.823). Median HADS scores were low: 5 (IQR 6) for anxiety and 3 (IQR 5) for depression, and they were unaffe
Published: 2020
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5. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Author: Terry, M-B. (Mary-beth), Liao, Y.Y., Kast, K. (Karin), Antoniou, A.C. (Antonis), McDonald, JA, Mooij, T.M. (Thea), Engel, C., Nogues, C. (Catherine), Buecher, B. (Bruno), Mari, V., Moretta-Serra, J., Gladieff, L, Luporsi, E., Barrowdale, D. (Daniel), Frost, D. (Debra), Henderson, A, Brewer, C. (C.), Evans, DGR, Eccles, D. (Diana), Cook, J. (Jackie), Ong, K.-R. (Kai-Ren), Izatt, L. (Louise), Ahmed, M., Morrison, P.J. (Patrick), Dommering, C.J. (Charlotte), Oosterwijk, J.C. (Jan), Ausems, M.G.E.M. (Margreet), Kriege, M., Buys, S.S. (Saundra), Andrulis, I.L. (Irene), John, E.M. (Esther), Daly, M.J. (Mark), Friedlander, M. (Michael), McLachlan, SA, Osorio, A. (Ana), Caldes, T. (Trinidad), Jakubowska, A. (Anna), Simard, J. (Jacques), Singer, C.F. (Christian), Tan, Y.H. (Yao Hua), Olah, E., Navratilova, M, Foretova, L. (Lenka), Gerdes, A-M. (Anne-Marie), Roos-Blom, M.J., Arver, B. (Brita Wasteson), Olsson, H. (Hans), Schmutzler, R.K. (Rita), Hopper, J. (John), Leeuwen, F.E. (Flora) van, Goldgar, D. (David), Milne, R.L. (Roger), Easton, D.F. (Douglas), Rookus, M.A. (M.), Andrieu, N, Evans, D.G. (Gareth), Adlard, J.W. (Julian), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Tischkowitz, M. (Marc), Snape, K., Walker, L.J. (Lisa), Porteous, M.E. (Mary), Donaldson, A. (Alan), Morrison, P, Eason, J. (Jacqueline), Rogers, M, Miller, C, Brady, A, Kennedy, M.J. (John), Barwell, J. (Julian), Gregory, H. (Helen), Pottinger, C. (Caroline), Murray, A. (Anna), Angelakos, M., Dite, G., Tsimiklis, H. (Helen), Breysse, E., Pontois, P., Laborde, L., Stoppa-Lyonnet, D. (Dominique), Gauthier-Villars, M. (Marion), Caron, O. (Olivier), Fourme-Mouret, E., Fricker, J.P. (Jean Pierre), Lasset, C. (Christine), Bonadona, V. (Valérie), Fert-Ferrer, S. (Sandra), Berthet, P. (Pascaline), Vénat-Bouvet, L. (Laurence), Gilbert-Dussardier, B., Faivre, L. (Laurence), Gesta, P., Sobol, H. (Hagay), Eisinger, F. (François), Longy, M. (Michel), Dugast, C., Coupier, I. (Isabelle), Colas, C. (Chrystelle), Soubrier, F., Pujol, P. (Pascal), Corsini, C., Lortholary, A, Vennin, P. (Philippe), Adenis, C., Nguyen, T.D., Penet, C., Delnatte, C.D. (Capucine), Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Demange, L., Dreyfus, H. (Hélène), Cohen-Haguenauer, O. (Odile), Leroux, D. (Dominique), Zattara-Cannoni, H., Bera, O., Hogervorst, F.B.L. (Frans), Adank, M.A. (Muriel), Schmidt, M.K. (Marjanka), Russell, N.S. (Nicola), Jenner, D.J., Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Devilee, P. (P.), Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Koudijs, MJ, Aalfs, C.M. (Cora), Engelen, K. (Klaartje) van, Gille, J.J. (Johan), Gómez García, E.B. (Encarna), Blok, M.J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Siesling, S. (Sabine), Verloop, H. (Herman), Belt-Dusebout, A.W. (Alexandra) van den, Terry, M-B. (Mary-beth), Liao, Y.Y., Kast, K. (Karin), Antoniou, A.C. (Antonis), McDonald, JA, Mooij, T.M. (Thea), Engel, C., Nogues, C. (Catherine), Buecher, B. (Bruno), Mari, V., Moretta-Serra, J., Gladieff, L, Luporsi, E., Barrowdale, D. (Daniel), Frost, D. (Debra), Henderson, A, Brewer, C. (C.), Evans, DGR, Eccles, D. (Diana), Cook, J. (Jackie), Ong, K.-R. (Kai-Ren), Izatt, L. (Louise), Ahmed, M., Morrison, P.J. (Patrick), Dommering, C.J. (Charlotte), Oosterwijk, J.C. (Jan), Ausems, M.G.E.M. (Margreet), Kriege, M., Buys, S.S. (Saundra), Andrulis, I.L. (Irene), John, E.M. (Esther), Daly, M.J. (Mark), Friedlander, M. (Michael), McLachlan, SA, Osorio, A. (Ana), Caldes, T. (Trinidad), Jakubowska, A. (Anna), Simard, J. (Jacques), Singer, C.F. (Christian), Tan, Y.H. (Yao Hua), Olah, E., Navratilova, M, Foretova, L. (Lenka), Gerdes, A-M. (Anne-Marie), Roos-Blom, M.J., Arver, B. (Brita Wasteson), Olsson, H. (Hans), Schmutzler, R.K. (Rita), Hopper, J. (John), Leeuwen, F.E. (Flora) van, Goldgar, D. (David), Milne, R.L. (Roger), Easton, D.F. (Douglas), Rookus, M.A. (M.), Andrieu, N, Evans, D.G. (Gareth), Adlard, J.W. (Julian), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Tischkowitz, M. (Marc), Snape, K., Walker, L.J. (Lisa), Porteous, M.E. (Mary), Donaldson, A. (Alan), Morrison, P, Eason, J. (Jacqueline), Rogers, M, Miller, C, Brady, A, Kennedy, M.J. (John), Barwell, J. (Julian), Gregory, H. (Helen), Pottinger, C. (Caroline), Murray, A. (Anna), Angelakos, M., Dite, G., Tsimiklis, H. (Helen), Breysse, E., Pontois, P., Laborde, L., Stoppa-Lyonnet, D. (Dominique), Gauthier-Villars, M. (Marion), Caron, O. (Olivier), Fourme-Mouret, E., Fricker, J.P. (Jean Pierre), Lasset, C. (Christine), Bonadona, V. (Valérie), Fert-Ferrer, S. (Sandra), Berthet, P. (Pascaline), Vénat-Bouvet, L. (Laurence), Gilbert-Dussardier, B., Faivre, L. (Laurence), Gesta, P., Sobol, H. (Hagay), Eisinger, F. (François), Longy, M. (Michel), Dugast, C., Coupier, I. (Isabelle), Colas, C. (Chrystelle), Soubrier, F., Pujol, P. (Pascal), Corsini, C., Lortholary, A, Vennin, P. (Philippe), Adenis, C., Nguyen, T.D., Penet, C., Delnatte, C.D. (Capucine), Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Demange, L., Dreyfus, H. (Hélène), Cohen-Haguenauer, O. (Odile), Leroux, D. (Dominique), Zattara-Cannoni, H., Bera, O., Hogervorst, F.B.L. (Frans), Adank, M.A. (Muriel), Schmidt, M.K. (Marjanka), Russell, N.S. (Nicola), Jenner, D.J., Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Devilee, P. (P.), Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Koudijs, MJ, Aalfs, C.M. (Cora), Engelen, K. (Klaartje) van, Gille, J.J. (Johan), Gómez García, E.B. (Encarna), Blok, M.J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Siesling, S. (Sabine), Verloop, H. (Herman), and Belt-Dusebout, A.W. (Alexandra) van den
Abstract: Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95% CI ¼ 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
Published: 2019

6. The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Author: Terry, M-B. (Mary-beth), Liao, Y.Y., Kast, K. (Karin), Antoniou, A.C. (Antonis), McDonald, JA, Mooij, T.M. (Thea), Engel, C., Nogues, C. (Catherine), Buecher, B. (Bruno), Mari, V., Moretta-Serra, J., Gladieff, L, Luporsi, E., Barrowdale, D. (Daniel), Frost, D. (Debra), Henderson, A, Brewer, C. (C.), Evans, DGR, Eccles, D. (Diana), Cook, J. (Jackie), Ong, K.-R. (Kai-Ren), Izatt, L. (Louise), Ahmed, M., Morrison, P.J. (Patrick), Dommering, C.J. (Charlotte), Oosterwijk, J.C. (Jan), Ausems, M.G.E.M. (Margreet), Kriege, M., Buys, S.S. (Saundra), Andrulis, I.L. (Irene), John, E.M. (Esther), Daly, M.J. (Mark), Friedlander, M. (Michael), McLachlan, SA, Osorio, A. (Ana), Caldes, T. (Trinidad), Jakubowska, A. (Anna), Simard, J. (Jacques), Singer, C.F. (Christian), Tan, Y.H. (Yao Hua), Olah, E., Navratilova, M, Foretova, L. (Lenka), Gerdes, A-M. (Anne-Marie), Roos-Blom, M.J., Arver, B. (Brita Wasteson), Olsson, H. (Hans), Schmutzler, R.K. (Rita), Hopper, J. (John), Leeuwen, F.E. (Flora) van, Goldgar, D. (David), Milne, R.L. (Roger), Easton, D.F. (Douglas), Rookus, M.A. (M.), Andrieu, N, Evans, D.G. (Gareth), Adlard, J.W. (Julian), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Tischkowitz, M. (Marc), Snape, K., Walker, L.J. (Lisa), Porteous, M.E. (Mary), Donaldson, A. (Alan), Morrison, P, Eason, J. (Jacqueline), Rogers, M, Miller, C, Brady, A, Kennedy, M.J. (John), Barwell, J. (Julian), Gregory, H. (Helen), Pottinger, C. (Caroline), Murray, A. (Anna), Angelakos, M., Dite, G., Tsimiklis, H. (Helen), Breysse, E., Pontois, P., Laborde, L., Stoppa-Lyonnet, D. (Dominique), Gauthier-Villars, M. (Marion), Caron, O. (Olivier), Fourme-Mouret, E., Fricker, J.P. (Jean Pierre), Lasset, C. (Christine), Bonadona, V. (Valérie), Fert-Ferrer, S. (Sandra), Berthet, P. (Pascaline), Vénat-Bouvet, L. (Laurence), Gilbert-Dussardier, B., Faivre, L. (Laurence), Gesta, P., Sobol, H. (Hagay), Eisinger, F. (François), Longy, M. (Michel), Dugast, C., Coupier, I. (Isabelle), Colas, C. (Chrystelle), Soubrier, F., Pujol, P. (Pascal), Corsini, C., Lortholary, A, Vennin, P. (Philippe), Adenis, C., Nguyen, T.D., Penet, C., Delnatte, C.D. (Capucine), Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Demange, L., Dreyfus, H. (Hélène), Cohen-Haguenauer, O. (Odile), Leroux, D. (Dominique), Zattara-Cannoni, H., Bera, O., Hogervorst, F.B.L. (Frans), Adank, M.A. (Muriel), Schmidt, M.K. (Marjanka), Russell, N.S. (Nicola), Jenner, D.J., Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Devilee, P. (P.), Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Koudijs, MJ, Aalfs, C.M. (Cora), Engelen, K. (Klaartje) van, Gille, J.J. (Johan), Gómez García, E.B. (Encarna), Blok, M.J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Siesling, S. (Sabine), Verloop, H. (Herman), Belt-Dusebout, A.W. (Alexandra) van den, Terry, M-B. (Mary-beth), Liao, Y.Y., Kast, K. (Karin), Antoniou, A.C. (Antonis), McDonald, JA, Mooij, T.M. (Thea), Engel, C., Nogues, C. (Catherine), Buecher, B. (Bruno), Mari, V., Moretta-Serra, J., Gladieff, L, Luporsi, E., Barrowdale, D. (Daniel), Frost, D. (Debra), Henderson, A, Brewer, C. (C.), Evans, DGR, Eccles, D. (Diana), Cook, J. (Jackie), Ong, K.-R. (Kai-Ren), Izatt, L. (Louise), Ahmed, M., Morrison, P.J. (Patrick), Dommering, C.J. (Charlotte), Oosterwijk, J.C. (Jan), Ausems, M.G.E.M. (Margreet), Kriege, M., Buys, S.S. (Saundra), Andrulis, I.L. (Irene), John, E.M. (Esther), Daly, M.J. (Mark), Friedlander, M. (Michael), McLachlan, SA, Osorio, A. (Ana), Caldes, T. (Trinidad), Jakubowska, A. (Anna), Simard, J. (Jacques), Singer, C.F. (Christian), Tan, Y.H. (Yao Hua), Olah, E., Navratilova, M, Foretova, L. (Lenka), Gerdes, A-M. (Anne-Marie), Roos-Blom, M.J., Arver, B. (Brita Wasteson), Olsson, H. (Hans), Schmutzler, R.K. (Rita), Hopper, J. (John), Leeuwen, F.E. (Flora) van, Goldgar, D. (David), Milne, R.L. (Roger), Easton, D.F. (Douglas), Rookus, M.A. (M.), Andrieu, N, Evans, D.G. (Gareth), Adlard, J.W. (Julian), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Tischkowitz, M. (Marc), Snape, K., Walker, L.J. (Lisa), Porteous, M.E. (Mary), Donaldson, A. (Alan), Morrison, P, Eason, J. (Jacqueline), Rogers, M, Miller, C, Brady, A, Kennedy, M.J. (John), Barwell, J. (Julian), Gregory, H. (Helen), Pottinger, C. (Caroline), Murray, A. (Anna), Angelakos, M., Dite, G., Tsimiklis, H. (Helen), Breysse, E., Pontois, P., Laborde, L., Stoppa-Lyonnet, D. (Dominique), Gauthier-Villars, M. (Marion), Caron, O. (Olivier), Fourme-Mouret, E., Fricker, J.P. (Jean Pierre), Lasset, C. (Christine), Bonadona, V. (Valérie), Fert-Ferrer, S. (Sandra), Berthet, P. (Pascaline), Vénat-Bouvet, L. (Laurence), Gilbert-Dussardier, B., Faivre, L. (Laurence), Gesta, P., Sobol, H. (Hagay), Eisinger, F. (François), Longy, M. (Michel), Dugast, C., Coupier, I. (Isabelle), Colas, C. (Chrystelle), Soubrier, F., Pujol, P. (Pascal), Corsini, C., Lortholary, A, Vennin, P. (Philippe), Adenis, C., Nguyen, T.D., Penet, C., Delnatte, C.D. (Capucine), Tinat, J., Tennevet, I., Limacher, J.M., Maugard, C., Demange, L., Dreyfus, H. (Hélène), Cohen-Haguenauer, O. (Odile), Leroux, D. (Dominique), Zattara-Cannoni, H., Bera, O., Hogervorst, F.B.L. (Frans), Adank, M.A. (Muriel), Schmidt, M.K. (Marjanka), Russell, N.S. (Nicola), Jenner, D.J., Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Devilee, P. (P.), Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Koudijs, MJ, Aalfs, C.M. (Cora), Engelen, K. (Klaartje) van, Gille, J.J. (Johan), Gómez García, E.B. (Encarna), Blok, M.J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Siesling, S. (Sabine), Verloop, H. (Herman), and Belt-Dusebout, A.W. (Alexandra) van den
Abstract: Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95% CI ¼ 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
Published: 2019

7. Preferences to receive unsolicited findings of germline genome sequencing in a large population of patients with cancer

Author: Bijlsma, R., Wouters, R., Wessels, H. (Hans), Sleijfer, S. (Stefan), Beerepoot, L, Huinink, DT, Cruijsen, H., Heijns, J., Lolkema, M.P.J.K., Steeghs, N. (Neeltje), van Voorthuizen, T., Vulink, A., Witteveen, E., Ausems, M.G.E.M. (Margreet), Bredenoord, A., May, A.M. (Anne), Voest, E, Bijlsma, R., Wouters, R., Wessels, H. (Hans), Sleijfer, S. (Stefan), Beerepoot, L, Huinink, DT, Cruijsen, H., Heijns, J., Lolkema, M.P.J.K., Steeghs, N. (Neeltje), van Voorthuizen, T., Vulink, A., Witteveen, E., Ausems, M.G.E.M. (Margreet), Bredenoord, A., May, A.M. (Anne), and Voest, E
Abstract: Background In precision medicine, somatic and germline DNA sequencing are essential to make genome-guided treatment decisions in patients with cancer. However, it can also uncover unsolicited findings (UFs) in germline DNA that could have a substantial impact on the lives of patients and their relatives. It is therefore critical to understand the preferences of patients with cancer concerning UFs derived from whole-exome (WES) or whole-genome sequencing (WGS). Methods In a quantitative multicentre study, adult patients with cancer (any stage and origin of disease) were surveyed through a digital questionnaire based on previous semi-structured interviews. Background knowledge was provided by showing two videos, introducing basic concepts of genetics and general information about different categories of UFs (actionable, non-actionable, reproductive significance, unknown significance). Results In total 1072 patients were included of whom 701 participants completed the whole questionnaire. Overall, 686 (85.1%) participants wanted to be informed about UFs in general. After introduction of four UFs categories, 113 participants (14.8%) changed their answer: 718 (94.2%) participants opted for actionable variants, 537 (72.4%) for non-actionable variants, 635 (87.0%) participants for UFs of reproductive significance and 521 (71.8%) for UFs of unknown significance. Men were more interested in receiving certain UFs than women: non-actionable: OR 3.32; 95%CI 2.05 to 5.37, reproductive significance: OR 1.97; 95%CI 1.05 to 3.67 and unknown significance: OR 2.00; 95%CI 1.25 to 3.21. In total, 244 (33%) participants conceded family members to have access to their UFs while still alive. 603 (82%) participants agreed to information being shared with relatives, after they would pass away. Conclusion Our study showed that the vast majority of patients with cancer desires to receive all UFs of genome testing, although a substantial minority does not wish to receive non-actionable finding
Published: 2019
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8. Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers

Author: Heemskerk-Gerritsen, B.A.M. (Bernadette), Jager, A. (Agnes), Koppert, L.B. (Linetta), Obdeijn, A.I.M. (Inge-Marie), Collée, J.M. (Margriet), Meijers-Heijboer, HE, Jenner, D.J., Oldenburg, H.S.A., Engelen, K. (Klaartje) van, Vries, J. (Jelle) de, Asperen, C.J. (Christi) van, Devilee, P. (P.), Blok, M.J.C., Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Seynaeve, C., Rookus, M.A. (M.), Hooning, M.J. (Maartje), Heemskerk-Gerritsen, B.A.M. (Bernadette), Jager, A. (Agnes), Koppert, L.B. (Linetta), Obdeijn, A.I.M. (Inge-Marie), Collée, J.M. (Margriet), Meijers-Heijboer, HE, Jenner, D.J., Oldenburg, H.S.A., Engelen, K. (Klaartje) van, Vries, J. (Jelle) de, Asperen, C.J. (Christi) van, Devilee, P. (P.), Blok, M.J.C., Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Seynaeve, C., Rookus, M.A. (M.), and Hooning, M.J. (Maartje)
Abstract: Background In healthy BRCA1/2 mutation carriers, bilateral risk-reducing mastectomy (BRRM) strongly reduces the risk of developing breast cancer (BC); however, no clear survival beneft of BRRM over BC surveillance has been reported yet. Methods In this Dutch multicenter cohort study, we used multivariable Cox models with BRRM as a time-dependent covariable to estimate the associations between BRRM and the overall and BC-specifc mortality rates, separately for BRCA1 and BRCA2 mutation carriers. Results During a mean follow-up of 10.3 years, 722 out of 1712 BRCA1 (42%) and 406 out of 1145 BRCA2 (35%) mutation carriers underwent BRRM. For BRCA1 mutation carriers, we observed 52 deaths (20 from BC) in the surveillance group, and 10 deaths (one from BC) after BRRM. The hazard ratios were 0.40 (95% CI 0.20–0.90) for overall mortality and 0.06 (95% CI 0.01–0.46) for BC-specifc mortality. BC-specifc survival at age 65 was 93% for surveillance and 99.7% for BRRM. For BRCA2 mutation carriers, we observed 29 deaths (7 from BC) in the surveillance group, and 4 deaths (no BC) after BRRM. The hazard ratio for overall mortality was 0.45 (95% CI 0.15–1.36). BC-specifc survival at age 65 was 98% for surveillance and 100% for BRRM. Conclusion BRRM was associated with lower mortality than surveillance for BRCA1 mutation carriers, but for BRCA2 mutation carriers, BRRM may lead to similar BC-specifc survival as surveillance. Our fndings support a more individualized counseling based on BRCA mutation type.
Published: 2019
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9. ‘We don’t know for sure’: discussion of uncertainty concerning multigene panel testing during initial cancer genetic consultations

Author: Medendorp, N.M. (Niki M.), Hillen, M.A. (Marij A.), van Maarschalkerweerd, P.E.A. (Pomme E. A.), Aalfs, C.M. (Cora), Ausems, M.G.E.M. (Margreet), Verhoef, S. (Senno), Kolk, L.E. (Lizet) van der, Berger, L.P.V. (Lieke P. V.), Wevers, M.R., Wagner, A. (Anja), Caanen, B., Stiggelbout, A.M. (Anne), Smets, E.M.A. (Ellen), Medendorp, N.M. (Niki M.), Hillen, M.A. (Marij A.), van Maarschalkerweerd, P.E.A. (Pomme E. A.), Aalfs, C.M. (Cora), Ausems, M.G.E.M. (Margreet), Verhoef, S. (Senno), Kolk, L.E. (Lizet) van der, Berger, L.P.V. (Lieke P. V.), Wevers, M.R., Wagner, A. (Anja), Caanen, B., Stiggelbout, A.M. (Anne), and Smets, E.M.A. (Ellen)
Abstract: Pre-test counseling about multigene panel testing involves many uncertainties. Ideally, counselees are informed about uncertainties in a way that enables them to make an informed decision about panel testing. It is presently unknown whether and how uncertainty is discussed during initial cancer genetic counseling. We therefore investigated whether and how counselors discuss and address uncertainty, and the extent of shared decision-making (SDM), and explored associations between counselors’ communication and their characteristics in consultations on panel testing for cancer. For this purpose, consultations of counselors discussing a multigene panel with a simulated patient were videotaped. Simulated patients represented a counselee who had had multiple cancer types, according to a script. Before and afterwards, counselors completed a survey. Counselors’ uncertainty expressions, initiating and the framing of expressions, and their verbal responses to scripted uncertainties of the simulated patient were coded by two researchers independently. Coding was done according to a pre-developed coding scheme using The Observer XT software for observational analysis. Additionally, the degree of SDM was assessed by two observers. Correlation and regression analyses were performed to assess associations of communicated uncertainties, responses and the extent of SDM, with counselors’ background characteristics. In total, twenty-nine counselors, including clinical geneticists, genetic counselors, physician assistants-in-training, residents and interns, participated of whom working experience varied between 0 and 25 years. Counselors expressed uncertainties mainly regarding scientific topics (94%) and on their own initiative (95%). Most expressions were framed directly (77%), e.g. We don’t know, and were emotionally neutral (59%; without a positive/negative value). Counselors mainly responded to uncertainties of the simulated patient by explicitly referring to the uncertainty (69%)
Published: 2019
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10. Ovarian stimulation for IVF and risk of primary breast cancer in BRCA1/2 mutation carriers

Author: Derks-Smeets, I.A.P. (Inge A. P.), Schrijver, L.H. (Lieske), Die-Smulders, C. (Christine) de, Tjan-Heijnen, V.C.G. (Vivianne), Golde, R.J.T. (Ronald) van, Smits, L.J. (Luc), Caanen, B., van Asperen, C.J. (Christi J.), Ausems, M.G.E.M. (Margreet), Collée, J.M. (Margriet), Engelen, K. (Klaartje) van, Kets, C.M. (Marleen), Kolk, L.E. (Lizet) van der, Oosterwijk, J.C. (Jan), Os, T.A.M. (Theo) van, Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Gómez García, E.B. (Encarna), Derks-Smeets, I.A.P. (Inge A. P.), Schrijver, L.H. (Lieske), Die-Smulders, C. (Christine) de, Tjan-Heijnen, V.C.G. (Vivianne), Golde, R.J.T. (Ronald) van, Smits, L.J. (Luc), Caanen, B., van Asperen, C.J. (Christi J.), Ausems, M.G.E.M. (Margreet), Collée, J.M. (Margriet), Engelen, K. (Klaartje) van, Kets, C.M. (Marleen), Kolk, L.E. (Lizet) van der, Oosterwijk, J.C. (Jan), Os, T.A.M. (Theo) van, Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, and Gómez García, E.B. (Encarna)
Abstract: Background: The effect of in vitro fertilisation (IVF) on breast cancer risk for BRCA1/2 mutation carriers is rarely examined. As carriers may increasingly undergo IVF as part of preimplantation genetic diagnosis (PGD), we examined the impact of ovarian stimulation for IVF on breast cancer risk in BRCA1/2 mutation carriers. Methods: The study population consisted of 1550 BRCA1 and 964 BRCA2 mutation carriers, derived from the nationwide HEBON study and the nationwide PGD registry. Questionnaires, clinical records and linkages with the Netherlands Cancer Registry were used to collect data on IVF exposure, risk-reducing surgeries and cancer diagnosis, respectively. Time-dependent Cox regression analyses were conducted, stratified for birth cohort and adjusted for subfertility. Results: Of the 2514 BRCA1/2 mutation carriers, 3% (n = 76) were exposed to ovarian stimulation for IVF. In total, 938 BRCA1/2 mutation carriers (37.3%) were diagnosed with breast cancer. IVF exposure was not associated with risk of breast cancer (HR: 0.79, 95% CI: 0.46–1.36). Similar results were found for the subgroups of subfertile women (n = 232; HR: 0.73, 95% CI: 0.39–1.37) and BRCA1 mutation carriers (HR: 1.12, 95% CI: 0.60–2.09). In addition, age at and recency of first IVF treatment were not associated with breast cancer risk. Conclusion: No evidence was found for an association between ovarian stimulation for IVF and breast cancer risk in BRCA1/2 mutation carriers.
Published: 2018
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11. Online decision support for persons having a genetic predisposition to cancer and their partners during reproductive decision-making

Author: Reumkens, K. (Kelly), Tummers, M.H.E. (Marly), Gietel-Habets, J.J.G. (Joyce), Kuijk, S.M.J. (Sander) van, Aalfs, C.M. (Cora), Asperen, C.J. (Christi) van, Ausems, M.G.E.M. (Margreet), Collée, J.M. (Margriet), Dommering, C.J. (Charlotte), Kets, C.M. (Marleen), Kolk, L.E. (Lizet) van der, Oosterwijk, J.C. (Jan), Tjan-Heijnen, V.C.G. (Vivianne), Weijden, T. (Trudy) van der, Die-Smulders, C. (Christine) de, Osch, L.A.D.M. (Liesbeth) van, Reumkens, K. (Kelly), Tummers, M.H.E. (Marly), Gietel-Habets, J.J.G. (Joyce), Kuijk, S.M.J. (Sander) van, Aalfs, C.M. (Cora), Asperen, C.J. (Christi) van, Ausems, M.G.E.M. (Margreet), Collée, J.M. (Margriet), Dommering, C.J. (Charlotte), Kets, C.M. (Marleen), Kolk, L.E. (Lizet) van der, Oosterwijk, J.C. (Jan), Tjan-Heijnen, V.C.G. (Vivianne), Weijden, T. (Trudy) van der, Die-Smulders, C. (Christine) de, and Osch, L.A.D.M. (Liesbeth) van
Abstract: A nationwide pretest–posttest study was conducted in all clinical genetic centres in the Netherlands, to evaluate the effects of an online decision aid to support persons who have a genetic predisposition to cancer and their partners in making an informed decision regarding reproductive options. Main outcomes (decisional conflict, knowledge, realistic expectations, level of deliberation, and decision self‐efficacy) were measured before use (T0), immediately after use (T1), and at 2 weeks (T2) after use of the decision aid. Paired sample t tests were used to compute differences between the first and subsequent measurements. T0–T1 and T0–T2 comparisons indicate a significant reduction in mean decisional conflict scores with stronger effects for participants with high baseline deci‐ sional conflict. Furthermore, use of the decision aid resulted in increased knowledge levels and improved realistic expectations. Level of deliberation only increased for partici‐ pants with lower baseline levels of deliberation. Decision self‐efficacy increased for those with low baseline scores, whereas those with high baseline scores showed a reduction at T2. It can be concluded that use of the decision aid resulted in several positive outcomes indicative of informed decision‐making. The decision aid is an appropriate and highly ap‐ preciated tool to be used in addition to reproductive counseling.
Published: 2018
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12. The development of an online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making: a usability and pilot study

Author: Reumkens, K. (Kelly), Tummers, M.H.E. (Marly H. E.), Gietel-Habets, J.J.G. (Joyce J. G.), Kuijk, S.M.J. (Sander) van, Aalfs, C.M. (Cora), van Asperen, C.J. (Christi J.), Ausems, M.G.E.M. (Margreet), Collée, J.M. (Margriet), Dommering, C.J. (Charlotte), Kets, C.M. (Marleen), Kolk, L.E. (Lizet) van der, Oosterwijk, J.C. (Jan), Tjan-Heijnen, V.C.G. (Vivianne), Weijden, T. (Trudy) van der, Die-Smulders, C. (Christine) de, van Osch, L.A.D.M. (Liesbeth A. D. M.), Reumkens, K. (Kelly), Tummers, M.H.E. (Marly H. E.), Gietel-Habets, J.J.G. (Joyce J. G.), Kuijk, S.M.J. (Sander) van, Aalfs, C.M. (Cora), van Asperen, C.J. (Christi J.), Ausems, M.G.E.M. (Margreet), Collée, J.M. (Margriet), Dommering, C.J. (Charlotte), Kets, C.M. (Marleen), Kolk, L.E. (Lizet) van der, Oosterwijk, J.C. (Jan), Tjan-Heijnen, V.C.G. (Vivianne), Weijden, T. (Trudy) van der, Die-Smulders, C. (Christine) de, and van Osch, L.A.D.M. (Liesbeth A. D. M.)
Abstract: An online decision aid to support persons having a genetic predisposition to cancer and their partners during reproductive decision-making was developed. A two-phase usability test was conducted among 12 couples (N = 22; 2 persons participated without their partner) at risk for hereditary cancer and 15 health care providers. Couples and health care providers expressed similar suggestions for improvements, and evaluated the modified decision aid as acceptable, easy to use, and comprehensible. The final decision aid was pilot tested (N = 16) with paired sample t tests comparing main outcomes (decisional conflict, knowledge, realistic expectations regarding the reproductive options and decision self-efficacy) before (T0), immediately (T1) and 2 weeks after (T2) use of the decision aid. Pilot testing indicated decreased decisional conflict scores, increased knowledge, and improved realistic expectations regarding the reproductive options, at T1 and T2. No effect was found for couples’ decision self-efficacy. The positive findings during usability testing were thus reflected in the pilot study. The decision aid will be further evaluated in a nationwide pretest–posttest study to facilitate implementation in the onco-genetic counselling setting. Ultimately, it is expected that the decision aid will enable end-users to make an informed decision.
Published: 2018
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13. Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer susceptibility

Author: Weren, R.D.A. (Robbert D. A.), Van Der Post, R.S. (Rachel S.), Vogelaar, I.P. (Ingrid P.), Van Krieken, J.H. (J. Han), Spruijt, L. (Liesbeth), Lubinski, J. (Jan), Jakubowska, A. (Anna), Teodorczyk, U. (Urszula), Aalfs, C.M. (Cora), Hest, L.P. (Liselotte) van, Oliveira, C. (Carla), Kamping, E. (Eveline), Schackert, H.K. (Hans), Ranzani, G.N. (Guglielmina N.), Gómez García, E.B. (Encarna), Hes, F.J. (Frederik), Holinski-Feder, E. (Elke), Genuardi, M. (Maurizio), Ausems, M.G.E.M. (Margreet), Sijmons, R.H. (Rolf), Wagner, A. (Anja), Kolk, L.E. (Lizet) van der, Cats, A. (Annemieke), Bjørnevoll, I. (Inga), Hoogerbrugge, N. (Nicoline), Ligtenberg, M.J. (Marjolijn), Weren, R.D.A. (Robbert D. A.), Van Der Post, R.S. (Rachel S.), Vogelaar, I.P. (Ingrid P.), Van Krieken, J.H. (J. Han), Spruijt, L. (Liesbeth), Lubinski, J. (Jan), Jakubowska, A. (Anna), Teodorczyk, U. (Urszula), Aalfs, C.M. (Cora), Hest, L.P. (Liselotte) van, Oliveira, C. (Carla), Kamping, E. (Eveline), Schackert, H.K. (Hans), Ranzani, G.N. (Guglielmina N.), Gómez García, E.B. (Encarna), Hes, F.J. (Frederik), Holinski-Feder, E. (Elke), Genuardi, M. (Maurizio), Ausems, M.G.E.M. (Margreet), Sijmons, R.H. (Rolf), Wagner, A. (Anja), Kolk, L.E. (Lizet) van der, Cats, A. (Annemieke), Bjørnevoll, I. (Inga), Hoogerbrugge, N. (Nicoline), and Ligtenberg, M.J. (Marjolijn)
Abstract: Background: In approximately 10% of all gastric cancer (GC) cases, a heritable cause is suspected. A subset of these cases have a causative germline CDH1 mutation; however, in most cases the cause remains unknown. Our objective was to assess to what extent these remaining cases may be explained by germline mutations in the novel candidate GC predisposing genes CTNNA1, MAP3K6 or MYD88. Methods: We sequenced a large cohort of unexplained young and/or familial patients with GC (n=286) without a CDH1germline mutation for germline variants affecting CTNNA1, MAP3K6 and MYD88 using a targeted next-generation sequencing approach based on single-molecule molecular inversion probes. Results: Predicted deleterious germline variants were not encountered in MYD88, but recurrently observed in CTNNA1 (n=2) and MAP3K6 (n=3) in our cohort of patients with GC. In contrast to deleterious variants in CTNNA1, deleterious variants in MAP3K6 also occur frequently in the general population. Conclusions: Based on our results MAP3K6 should no longer be considered a GC predisposition gene, whereas deleterious CTNNA1 variants are confirmed as an infrequent cause of GC susceptibility. Biallelic MYD88 germline mutations are at most a very rare cause of GC susceptibility as no additional cases were identified.
Published: 2018
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14. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

Author: Mikropoulos, C., Selkirk, C.G. (Christina), Saya, S. (Sibel), Bancroft, E.K. (Elizabeth), Vertosick, E. (Emily), Dadaev, T. (Tokhir), Brendler, C. (Charles), Page, E. (Elizabeth), Dias, A. (Alexander), Evans, D.G. (D Gareth), Rothwell, J. (Jeanette), Maehle, L., Axcrona, K., Richardson, K. (Kate), Eccles, D. (Diana), Jensen, T. (Thomas), Osther, P.J. (Palle J), Van Asperen, C.J. (Christi J), Vasen, H. (Hans), Kiemeney, L.A.L.M. (Bart), Ringelberg, J. (Janneke), Cybulski, C. (Cezary), Wokolorczyk, D. (Dominika), Hart, R. (Rachel), Glover, W. (Wayne), Lam, J. (Jimmy), Taylor, L. (Louise), Salinas, M., Feliubadaló, L. (L.), Oldenburg, R.A. (Rogier), Cremers, R.G.H.M. (Ruben), Verhaegh, G. (Gerald), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Cook, J. (Jackie), Rosario, K. (Karyna), Buys, S.S. (Saundra S), Conner, T. (Tom), Domchek, S.M. (Susan), Powers, J. (Jacquelyn), Ausems, M.G.E.M. (Margreet), Teixeira, M.R. (Manuel R), Maia, S. (Sofia), Izatt, L. (Louise), Schmutzler, R. (Rita), Rhiem, K. (Kerstin), Foulkes, W.D. (William), Boshari, T. (Talia), Davidson, R. (Rosemarie), Ruijs, M.W.G. (Marielle), Helderman-van den Enden, A.T.J.M. (Apollonia), Andrews, L. (Lesley), Walker, L.J. (Lisa), Snape, K. (Katie), Henderson, A. (Alex), Jobson, I. (Irene), Lindeman, G.J. (Geoffrey), Liljegren, A. (Annelie), Harris, M. (Marion), Adank, M.A. (Muriel), Kirk, J. (Judy), Taylor, A. (Amy), Susman, R. (Rachel), Chen-Shtoyerman, R. (Rakefet), Pachter, N. (Nicholas), Spigelman, A., Side, L. (Lucy), Zgajnar, J. (Janez), Mora, J. (Josefina), Brewer, C. (C.), Gadea, N. (Neus), Brady, A. (A.), Gallagher, D. (David), Os, T.A.M. (Theo) van, Donaldson, A. (Alan), Stefansdottir, V. (Vigdis), Barwell, J. (Julian), James, P.A. (Paul A), Murphy, D.G. (Declan), Friedman, E. (Eitan), Nicolai, N. (Nicola), Greenhalgh, T. (Trisha), Obeid, E. (Elias), Murthy, A.C. (Adeline C.), Copakova, L. (Lucia), McGrath, J. (John), Teo, S.-H. (Soo-Hwang), Strom, S. (Sara), Kast, K. (Karin), Leongamornlert, D.A. (Daniel A), Chamberlain, A. (Anthony), Pope, J. (Jenny), Newlin, A.C. (Anna C), Aaronson, N.K. (Neil), Ardern-Jones, A. (Audrey), Bangma, C.H. (Chris), Castro, E. (Elena), Dearnaley, D. (David), Eyfjord, J. (Jorunn), Falconer, A., Foster, C.S. (Christopher S), Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johannson, O.T. (Oskar), Khoo, V., Lubinski, J. (Jan), Grindedal, E.M. (Eli Marie), McKinley, E.T. (Enid), Shackleton, K. (Kylie), Mitra, A. (Anita), Moynihan, C., Rennert, G. (Gad), Suri, M. (Mohnish), Tricker, K. (Karen), Moss, S. (Sue), Kote-Jarai, Z., Vickers, A.J. (Andrew), Lilja, H. (Hans), Helfand, B.T. (Brian T), Eeles, R.A. (Rosalind A.), Mikropoulos, C., Selkirk, C.G. (Christina), Saya, S. (Sibel), Bancroft, E.K. (Elizabeth), Vertosick, E. (Emily), Dadaev, T. (Tokhir), Brendler, C. (Charles), Page, E. (Elizabeth), Dias, A. (Alexander), Evans, D.G. (D Gareth), Rothwell, J. (Jeanette), Maehle, L., Axcrona, K., Richardson, K. (Kate), Eccles, D. (Diana), Jensen, T. (Thomas), Osther, P.J. (Palle J), Van Asperen, C.J. (Christi J), Vasen, H. (Hans), Kiemeney, L.A.L.M. (Bart), Ringelberg, J. (Janneke), Cybulski, C. (Cezary), Wokolorczyk, D. (Dominika), Hart, R. (Rachel), Glover, W. (Wayne), Lam, J. (Jimmy), Taylor, L. (Louise), Salinas, M., Feliubadaló, L. (L.), Oldenburg, R.A. (Rogier), Cremers, R.G.H.M. (Ruben), Verhaegh, G. (Gerald), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Cook, J. (Jackie), Rosario, K. (Karyna), Buys, S.S. (Saundra S), Conner, T. (Tom), Domchek, S.M. (Susan), Powers, J. (Jacquelyn), Ausems, M.G.E.M. (Margreet), Teixeira, M.R. (Manuel R), Maia, S. (Sofia), Izatt, L. (Louise), Schmutzler, R. (Rita), Rhiem, K. (Kerstin), Foulkes, W.D. (William), Boshari, T. (Talia), Davidson, R. (Rosemarie), Ruijs, M.W.G. (Marielle), Helderman-van den Enden, A.T.J.M. (Apollonia), Andrews, L. (Lesley), Walker, L.J. (Lisa), Snape, K. (Katie), Henderson, A. (Alex), Jobson, I. (Irene), Lindeman, G.J. (Geoffrey), Liljegren, A. (Annelie), Harris, M. (Marion), Adank, M.A. (Muriel), Kirk, J. (Judy), Taylor, A. (Amy), Susman, R. (Rachel), Chen-Shtoyerman, R. (Rakefet), Pachter, N. (Nicholas), Spigelman, A., Side, L. (Lucy), Zgajnar, J. (Janez), Mora, J. (Josefina), Brewer, C. (C.), Gadea, N. (Neus), Brady, A. (A.), Gallagher, D. (David), Os, T.A.M. (Theo) van, Donaldson, A. (Alan), Stefansdottir, V. (Vigdis), Barwell, J. (Julian), James, P.A. (Paul A), Murphy, D.G. (Declan), Friedman, E. (Eitan), Nicolai, N. (Nicola), Greenhalgh, T. (Trisha), Obeid, E. (Elias), Murthy, A.C. (Adeline C.), Copakova, L. (Lucia), McGrath, J. (John), Teo, S.-H. (Soo-Hwang), Strom, S. (Sara), Kast, K. (Karin), Leongamornlert, D.A. (Daniel A), Chamberlain, A. (Anthony), Pope, J. (Jenny), Newlin, A.C. (Anna C), Aaronson, N.K. (Neil), Ardern-Jones, A. (Audrey), Bangma, C.H. (Chris), Castro, E. (Elena), Dearnaley, D. (David), Eyfjord, J. (Jorunn), Falconer, A., Foster, C.S. (Christopher S), Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johannson, O.T. (Oskar), Khoo, V., Lubinski, J. (Jan), Grindedal, E.M. (Eli Marie), McKinley, E.T. (Enid), Shackleton, K. (Kylie), Mitra, A. (Anita), Moynihan, C., Rennert, G. (Gad), Suri, M. (Mohnish), Tricker, K. (Karen), Moss, S. (Sue), Kote-Jarai, Z., Vickers, A.J. (Andrew), Lilja, H. (Hans), Helfand, B.T. (Brian T), and Eeles, R.A. (Rosalind A.)
Abstract: Background:Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort.Methods:PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV.Results:1634 participants had 3/43 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml -l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers.Conclusions:PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.
Published: 2018
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15. Factors associated with cancer worries in individuals participating in annual pancreatic cancer surveillance

Author: Konings, I.R.H.M. (Inge), Harinck, F. (Femme), Kuenen, M.A. (Marianne), Sidharta, G.N. (Grace N.), Kieffer, J.M. (Jacobien M.), Aalfs, C.M. (Cora), Poley, J.-W. (Jan-Werner), Smets, E.M.A. (Ellen), Wagner, A. (Anja), van Rens, A. (Anja), Vleggaar, F.P. (Frank), Ausems, M.G.E.M. (Margreet), Fockens, P. (Paul), Hooft, J.E. (Jeanin) van, Bruno, M.J. (Marco), Bleiker, E.M.A. (Eveline), On behalf of the Dutch research group on pancreatic cancer surveillance in high-risk individuals, (), Konings, I.R.H.M. (Inge), Harinck, F. (Femme), Kuenen, M.A. (Marianne), Sidharta, G.N. (Grace N.), Kieffer, J.M. (Jacobien M.), Aalfs, C.M. (Cora), Poley, J.-W. (Jan-Werner), Smets, E.M.A. (Ellen), Wagner, A. (Anja), van Rens, A. (Anja), Vleggaar, F.P. (Frank), Ausems, M.G.E.M. (Margreet), Fockens, P. (Paul), Hooft, J.E. (Jeanin) van, Bruno, M.J. (Marco), Bleiker, E.M.A. (Eveline), and On behalf of the Dutch research group on pancreatic cancer surveillance in high-risk individuals, ()
Abstract: It is important to adequately and timely identify individuals with cancer worries amongst participants in a pancreatic ductal adenocarcinoma (PDAC) surveillance program, because they could benefit from psychosocial support to decrease distress. Therefore, the aim of this study was to assess both psychosocial and clinical factors associated with cancer worries. High-risk individuals participating in PDAC-surveillance were invited to annually complete a cancer worry scale (CWS) questionnaire which was sent after counseling by the clinical geneticist (T0), after intake for participation in PDAC-surveillance (T1), and then annually after every MRI and endoscopic ultrasonography (EUS) (T2 and furthe
Published: 2017
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16. MEN1-dependent breast cancer: Indication for early screening? Results from the Dutch MEN1 study group

Author: Van Leeuwaarde, R.S. (Rachel S.), Dreijerink, K.M. (Koen M.), Ausems, M.G.E.M. (Margreet), Beijers, H.J. (Hanneke J.), Dekkers, O.M. (Olaf), Herder, W.W. (Wouter) de, Horst-Schrivers, A.N.A. (Anouk) van der, Drent, M.L. (Madeleine), Bisschop, P.H. (Peter), Havekes, B. (Bas), Peeters, P.H.M., Pijnappel, W.W.M.P. (Pim), Vriens, M.R. (Menno), Valk, G.D. (Gerlof), Van Leeuwaarde, R.S. (Rachel S.), Dreijerink, K.M. (Koen M.), Ausems, M.G.E.M. (Margreet), Beijers, H.J. (Hanneke J.), Dekkers, O.M. (Olaf), Herder, W.W. (Wouter) de, Horst-Schrivers, A.N.A. (Anouk) van der, Drent, M.L. (Madeleine), Bisschop, P.H. (Peter), Havekes, B. (Bas), Peeters, P.H.M., Pijnappel, W.W.M.P. (Pim), Vriens, M.R. (Menno), and Valk, G.D. (Gerlof)
Abstract: Copyright
Published: 2017
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17. Performance of BRCA1/2 mutation prediction models in male breast cancer patients

Author: Moghadasi, S. (Setareh), Grundeken, V. (V.), Janssen, L.A.M. (L. A.M.), Dijkstra, N.H. (N. H.), Rodríguez-Girondo, M. (M.), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Ausems, M.G.E.M. (Margreet), Oldenburg, R.A. (Rogier), Adank, M.A. (Muriel), Blom, E.W. (E. W.), Ruijs, M.W.G. (Marielle), Os, T.A.M. (Theo) van, Deurzen, C.H.M. (Carolien) van, Martens, J.W.M. (John), Schroder, C.P. (C. P.), Wijnen, J.T. (Juul), Vreeswijk, M.P. (Maaike), van Asperen, C.J. (C. J.), Moghadasi, S. (Setareh), Grundeken, V. (V.), Janssen, L.A.M. (L. A.M.), Dijkstra, N.H. (N. H.), Rodríguez-Girondo, M. (M.), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Ausems, M.G.E.M. (Margreet), Oldenburg, R.A. (Rogier), Adank, M.A. (Muriel), Blom, E.W. (E. W.), Ruijs, M.W.G. (Marielle), Os, T.A.M. (Theo) van, Deurzen, C.H.M. (Carolien) van, Martens, J.W.M. (John), Schroder, C.P. (C. P.), Wijnen, J.T. (Juul), Vreeswijk, M.P. (Maaike), and van Asperen, C.J. (C. J.)
Abstract: To establish whether existing mutation prediction models can identify which male breast cancer (MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm), BRCAPRO (BRCA probability) and the Myriad prevalence table ("Myriad"). These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed vs predicted carriers and assessed the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) for each model. BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% confidence interval [CI]: [0.60-1.09] and 0.79, 95% CI: [0.57-1.09], vs. BRCAPRO: 1.02, 95% CI: [0.75-1.38] and 0.94, 95% CI: [0.68-1.31], respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671). BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources.
Published: 2017
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18. Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

Author: Vogelaar, I.P. (Ingrid P.), Van Der Post, R.S. (Rachel S.), Van Krieken, J.H. (J. Han), Spruijt, L. (Liesbeth), Zelst-Stams, W.A. van, Kets, C.M. (Marleen), Lubinski, J. (Jan), Jakubowska, A. (Anna), Teodorczyk, U. (Urszula), Aalfs, C.M. (Cora), Hest, L.P. (Liselotte) van, Pinheiro, H. (Hugo), Oliveira, C. (Carla), Jhangiani, S.N. (Shalini N.), Muzny, D. (Donna), Gibbs, R.A. (Richard A.), Lupski, J.R. (James R.), Ligt, J. (Joep) de, Vissers, L.E.L.M., Hoischen, A. (Alex), Gilissen, C. (Christian), Van De Vorst, M. (Maartje), Goeman, J.J. (Jelle), Schackert, H.K. (Hans), Ranzani, G.N. (Guglielmina N.), Molinaro, V. (Valeria), Garcia, E.B.G., Hes, F.J. (Frederik), Holinski-Feder, E. (Elke), Genuardi, M. (Maurizio), Ausems, M.G.E.M. (Margreet), Sijmons, R.H. (Rolf), Wagner, A. (Anja), Kolk, L.E. (Lizet) van der, Bjørnevoll, I. (Inga), Høberg Vetti, H. (Hildegunn), Geurts van Kessel, A.H.M. (Ad), Kuiper, R. (Ruud), Ligtenberg, M.J. (Marjolijn), Hoogerbrugge, N. (Nicoline), Vogelaar, I.P. (Ingrid P.), Van Der Post, R.S. (Rachel S.), Van Krieken, J.H. (J. Han), Spruijt, L. (Liesbeth), Zelst-Stams, W.A. van, Kets, C.M. (Marleen), Lubinski, J. (Jan), Jakubowska, A. (Anna), Teodorczyk, U. (Urszula), Aalfs, C.M. (Cora), Hest, L.P. (Liselotte) van, Pinheiro, H. (Hugo), Oliveira, C. (Carla), Jhangiani, S.N. (Shalini N.), Muzny, D. (Donna), Gibbs, R.A. (Richard A.), Lupski, J.R. (James R.), Ligt, J. (Joep) de, Vissers, L.E.L.M., Hoischen, A. (Alex), Gilissen, C. (Christian), Van De Vorst, M. (Maartje), Goeman, J.J. (Jelle), Schackert, H.K. (Hans), Ranzani, G.N. (Guglielmina N.), Molinaro, V. (Valeria), Garcia, E.B.G., Hes, F.J. (Frederik), Holinski-Feder, E. (Elke), Genuardi, M. (Maurizio), Ausems, M.G.E.M. (Margreet), Sijmons, R.H. (Rolf), Wagner, A. (Anja), Kolk, L.E. (Lizet) van der, Bjørnevoll, I. (Inga), Høberg Vetti, H. (Hildegunn), Geurts van Kessel, A.H.M. (Ad), Kuiper, R. (Ruud), Ligtenberg, M.J. (Marjolijn), and Hoogerbrugge, N. (Nicoline)
Abstract: Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53 families with genetically unexplained diffuse-type and intestinal-type GC to identify novel GC-predisposing candidate genes. As young age at diagnosis and familial clustering are hallmarks of genetic tumor susceptibility, we selected patients that were diagnosed below the age of 35, patients from families with two cases of GC at or below age 60 and patients from families with three GC cases at or below age 70. All included individuals were tested negative for germline CDH1 mutations before or during the study. Variants that were possibly deleterious according to in silico predictions were filtered using several independent approaches that were based on gene function and gene mutation burden in controls. Despite a rigorous search, no obvious candidate GC predisposition genes were identified. This negative result stresses the importance of future research studies in large, homogeneous cohorts.
Published: 2017
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19. Unsolicited findings of next-generation sequencing for tumor analysis within a Dutch consortium: Clinical daily practice reconsidered

Author: Bijlsma, R.M. (Rhodé M), Bredenoord, A.L. (Annelien L), Gadellaa-Hooijdonk, C.G. (Christa G), Lolkema, M.P. (Martijn), Sleijfer, S. (Stefan), Voest, E.E. (Emile), Ausems, M.G.E.M. (Margreet), Steeghs, N. (Neeltje), Bijlsma, R.M. (Rhodé M), Bredenoord, A.L. (Annelien L), Gadellaa-Hooijdonk, C.G. (Christa G), Lolkema, M.P. (Martijn), Sleijfer, S. (Stefan), Voest, E.E. (Emile), Ausems, M.G.E.M. (Margreet), and Steeghs, N. (Neeltje)
Abstract: Cancer patients participating in studies involving experimental or diagnostic next-generation sequencing (NGS) procedures are confronted with the possibility of unsolicited findings. The Center for Personalized Cancer Treatment (CPCT), a Dutch consortium of cancer centers, is offering centralized large-scale NGS for the discovery of somatic tumor mutations with their germline DNA as reference. The CPCT aims to give all cancer patients with advanced disease stages access to tumor DNA analysis in order to improve selection for experimental therapy. In this article, our experiences at the CPCT will serve as an example to discuss the ethical and practical aspects regarding the management of unsolicited findings in personalized cancer research and treatment. Generic issues, relevant for all researchers in this field are discussed and illustrated by description of three patients faced with an unsolicited DNA finding, while they intended to be candidate for future anticancer treatment by participating in a trial that included NGS of both somatic and germline DNA. As options for DNA analysis expand and costs decrease rapidly, more and more patients are offered large-scale NGS testing. After reviewing current recommendations in literature, we conclude that classical informed consent procedures need to be adapted to become more explicit in asking patients if they want to be informed about unsolicited findings and if so, what level of detail of genetic risk information exactly they want to be returned after the analysis.
Published: 2016
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20. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Author: Lawrenson, K. (Kate), Kar, S. (Siddhartha), McCue, K. (Karen), Kuchenbaeker, K. (Karoline), Michailidou, K. (Kyriaki), Tyrer, J.P. (Jonathan), Beesley, J. (Jonathan), Ramus, S.J. (Susan), Li, Q. (Qiyuan), Delgado, M.K. (Melissa K.), Lee, J.M. (Janet M.), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Bandera, E.V. (Elisa), Barile, M. (Monica), Barkardottir, R.B. (Rosa B.), Barrowdale, D. (Daniel), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Berchuck, A. (Andrew), Bisogna, M. (Maria), Bjorge, L. (Line), Blomqvist, C. (Carl), Blot, W.J. (William), Bogdanova, N.V. (Natalia), Bojesen, A. (Anders), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Bonnani, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brennan, P. (Paul), Brenner, H. (Hermann), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buhari, S.A.B.S. (Shaik Ahmad Bin Syed), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Buys, S.S. (Saundra), Cai, Q. (Qiuyin), Caldes, T. (Trinidad), Campbell, I. (Ian), Canniotto, R. (Rikki), Chang-Claude, J. (Jenny), Chiquette, J. (Jocelyne), Choi, J.-Y. (Ji-Yeob), Claes, K.B.M. (Kathleen B.M.), Cook, L.S. (Linda S.), Cox, A. (Angela), Cramer, D.W. (Daniel), Cross, S.S. (Simon), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Dansonka-Mieszkowska, A. (Agnieszka), Darabi, H. (Hatef), Dennis, J. (Joe), Devilee, P. (Peter), Díez, O. (Orland), Doherty, J.A. (Jennifer A.), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dumont, M. (Martine), Ehrencrona, H. (Hans), Ejlertsen, B. (Bent), Ellis, S.D. (Steve), Engel, C. (Christoph), Lee, E. (Eunjung), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Feliubadaló, L. (L.), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foretova, L. (Lenka), Fostira, F. (Florentia), Foulkes, W.D. (William), Fridley, B.L. (Brooke), Friedman, E. (Eitan), Frost, D. (Debra), Gambino, G. (Gaetana), Ganz, P.A. (Patricia A.), Garber, J. (Judy), García-Closas, M. (Montserrat), Gentry-Maharaj, A. (Aleksandra), Ghoussaini, M. (Maya), Giles, G.G. (Graham), Glasspool, R. (Rosalind), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D. (David), González-Neira, A. (Anna), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Haiman, C.A. (Christopher A.), Hall, P. (Per), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), harrington, P. (Patricia), Hartman, J.M. (Joost), Hassan, N. (Norhashimah), Healey, S. (Sue), Heitz, P.U., Herzog, J. (Josef), Høgdall, E. (Estrid), Høgdall, C.K. (Claus), Hogervorst, F.B.L. (Frans), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Hulick, P.J. (Peter), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Ito, H. (Hidemi), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jensen, A. (Allan), John, E.M. (Esther), Johnson, N. (Nichola), Kabisch, M. (Maria), Kang, D. (Daehee), Kapuscinski, M.K. (Miroslav K.), Karlan, B.Y. (Beth Y.), Khan, S. (Sofia), Kiemeney, L.A.L.M. (Bart), Kjaer, M. (Michael), Knight, J.A. (Julia), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Hoya, M. (Miguel) de La, Laitman, Y. (Yael), Lambrechts, D. (Diether), Le, N.D. (Nhu D.), De Leeneer, K. (Kim), Lester, K.J. (Kathryn), Levine, D.A. (Douglas), Li, J. (Jingmei), Lindblom, A. (Annika), Long, J. (Jirong), Lophatananon, A. (Artitaya), Loud, J.T. (Jennifer), Lu, K.H. (Karen), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Le Marchand, L. (Loic), Margolin, S. (Sara), Marme, F. (Frederick), Massuger, L.F. (Leon), Matsuo, K. (Keitaro), Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), McLean, C.A. (Catriona Ann), McNeish, I. (Iain), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Milne, R.L. (Roger), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Muir, K.R. (K.), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nord, S. (Silje), Nussbaum, R.L. (Robert L.), Odunsi, K. (Kunle), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Orlow, I. (Irene), Orr, N. (Nick), Osorio, A. (Ana), Park, S.K. (Sue Kyung), Pearce, C.L. (Celeste), Pejovic, T. (Tanja), Peterlongo, P. (Paolo), Pfeiler, G. (Georg), Phelan, C. (Catherine), Poole, E.M. (Elizabeth), Pykäs, K. (Katri), Radice, P. (Paolo), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rhenius, V. (Valerie), Rhiem, K. (Kerstin), Risch, H. (Harvey), Rodriguez, G.C. (Gustavo), Rossing, M.A. (Mary Anne), Rudolph, A. (Anja), Salvesen, H.B. (Helga), Sangrajrang, S. (Suleeporn), Sawyer, E.J. (Elinor J.), Schildkraut, J.M. (Joellen), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Sellers, T.A. (Thomas A.), Seynaeve, C.M. (Caroline), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Sieh, W. (Weiva), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Slager, S. (Susan), Song, H. (Honglin), Soucy, P. (Penny), Southey, M.C. (Melissa), Stenmark-Askmalm, M. (Marie), Stoppa-Lyonnet, D. (Dominique), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Tchatchou, S. (Sandrine), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tibiletti, M.G. (Maria Grazia), Tihomirova, L. (Laima), Tognazzo, S. (Silvia), Toland, A.E. (Amanda), Tomlinson, I.P. (Ian), Torres, D. (Diana), Truong, T. (Thérèse), Tseng, C.-C. (Chiu-Chen), Tung, N. (Nadine), Tworoger, S.S. (Shelley S.), Vachon, C. (Celine), Van Den Ouweland, A.M.W. (Ans M.W.), Van Doorn, H.C. (Helena C.), Rensburg, E.J. (Elizabeth) van, Veer, L.J. (Laura) van 't, Vanderstichele, A. (Adriaan), Vergote, I. (Ignace), Vijai, J. (Joseph), Wang, Q. (Qin), Wang-Gohrke, S. (Shan), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wildiers, H. (Hans), Winqvist, R. (Robert), Wu, A.H. (Anna), Yannoukakos, D. (Drakoulis), Yoon, S.-Y. (Sook-Yee), Yu, J-C. (Jyh-Cherng), Zheng, W. (Wei), Zheng, Y. (Ying), Khanna, K.K. (Kum Kum), Simard, J. (Jacques), Monteiro, A.N.A. (Alvaro N.), French, J.D. (Juliet), Couch, F.J. (Fergus), Freedman, M. (Matthew), Easton, D.F. (Douglas F.), Dunning, A.M. (Alison), Pharoah, P.D.P. (Paul), Edwards, S.L. (Stacey), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Gayther, S.A. (Simon), Bowtell, D. (David), DeFazio, A. (Anna), Webb, P. (Penny), Collonge-Rame, M.-A., Damette, A. (Alexandre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Ferrer, S.F., Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Adenis, C. (Claude), Vénat-Bouvet, L. (Laurence), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Verny-Pierre, C. (Carole), Lasset, C. (Christine), Bonadona, V. (Valérie), Barjhoux, L. (Laure), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Coupier, I. (Isabelle), Pujol, P. (Pascal), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Delnatte, C.D. (Capucine), Bézieau, S. (Stéphane), Mari, V. (Véronique), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Rouleau, E. (Etienne), Golmard, L. (Lisa), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Pauw, A. (Antoine) de, Elan, C. (Camille), Fourme, E. (Emmanuelle), Birot, A.-M. (Anne-Marie), Saule, C. (Claire), Laurent, M. (Maïté), Houdayer, C. (Claude), Lesueur, F. (Fabienne), Mebirouk, N. (Noura), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Warcoin, M. (Mathilde), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Mortemousque, I. (Isabelle), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (John), Porteous, M.E. (Mary), Brady, A. (A.), Barwell, J. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L. (Lucy), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L.J. (Lisa), Cook, J. (Jackie), Snape, K. (Katie), Murray, A. (Alexandra), McCann, E. (Emma), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Kolk, L.E. (Lizet) van der, Russell, N.S. (Nicola), Lange, J.L. (J.) de, Wijnands, R., Collée, J.M. (Margriet), Hooning, M.J. (Maartje), Seynaeve, C., Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Pol, C. (Carmen) van der, Os, T.A.M. (Theo) van, Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Siesling, S., Verloop, J., Overbeek, L.I.H. (Lucy), Fox, S.B. (Stephen), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), Price, M. (Melanie), Lawrenson, K. (Kate), Kar, S. (Siddhartha), McCue, K. (Karen), Kuchenbaeker, K. (Karoline), Michailidou, K. (Kyriaki), Tyrer, J.P. (Jonathan), Beesley, J. (Jonathan), Ramus, S.J. (Susan), Li, Q. (Qiyuan), Delgado, M.K. (Melissa K.), Lee, J.M. (Janet M.), Aittomäki, K. (Kristiina), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Arndt, V. (Volker), Arun, B.K. (Banu), Arver, B. (Brita Wasteson), Bandera, E.V. (Elisa), Barile, M. (Monica), Barkardottir, R.B. (Rosa B.), Barrowdale, D. (Daniel), Beckmann, M.W. (Matthias), Benítez, J. (Javier), Berchuck, A. (Andrew), Bisogna, M. (Maria), Bjorge, L. (Line), Blomqvist, C. (Carl), Blot, W.J. (William), Bogdanova, N.V. (Natalia), Bojesen, A. (Anders), Bojesen, S.E. (Stig), Bolla, M.K. (Manjeet K.), Bonnani, B. (Bernardo), Borresen-Dale, A.-L. (Anne-Lise), Brauch, H. (Hiltrud), Brennan, P. (Paul), Brenner, H. (Hermann), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buhari, S.A.B.S. (Shaik Ahmad Bin Syed), Burwinkel, B. (Barbara), Butzow, R. (Ralf), Buys, S.S. (Saundra), Cai, Q. (Qiuyin), Caldes, T. (Trinidad), Campbell, I. (Ian), Canniotto, R. (Rikki), Chang-Claude, J. (Jenny), Chiquette, J. (Jocelyne), Choi, J.-Y. (Ji-Yeob), Claes, K.B.M. (Kathleen B.M.), Cook, L.S. (Linda S.), Cox, A. (Angela), Cramer, D.W. (Daniel), Cross, S.S. (Simon), Cybulski, C. (Cezary), Czene, K. (Kamila), Daly, M.B. (Mary B.), Damiola, F. (Francesca), Dansonka-Mieszkowska, A. (Agnieszka), Darabi, H. (Hatef), Dennis, J. (Joe), Devilee, P. (Peter), Díez, O. (Orland), Doherty, J.A. (Jennifer A.), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dumont, M. (Martine), Ehrencrona, H. (Hans), Ejlertsen, B. (Bent), Ellis, S.D. (Steve), Engel, C. (Christoph), Lee, E. (Eunjung), Evans, D.G. (D. Gareth), Fasching, P.A. (Peter), Feliubadaló, L. (L.), Figueroa, J.D. (Jonine), Flesch-Janys, D. (Dieter), Fletcher, O. (Olivia), Flyger, H. (Henrik), Foretova, L. (Lenka), Fostira, F. (Florentia), Foulkes, W.D. (William), Fridley, B.L. (Brooke), Friedman, E. (Eitan), Frost, D. (Debra), Gambino, G. (Gaetana), Ganz, P.A. (Patricia A.), Garber, J. (Judy), García-Closas, M. (Montserrat), Gentry-Maharaj, A. (Aleksandra), Ghoussaini, M. (Maya), Giles, G.G. (Graham), Glasspool, R. (Rosalind), Godwin, A.K. (Andrew K.), Goldberg, M.S. (Mark), Goldgar, D. (David), González-Neira, A. (Anna), Goode, E.L. (Ellen), Goodman, M.T. (Marc), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Guénel, P. (Pascal), Haiman, C.A. (Christopher A.), Hall, P. (Per), Hallberg, E. (Emily), Hamann, U. (Ute), Hansen, T.V.O. (Thomas), harrington, P. (Patricia), Hartman, J.M. (Joost), Hassan, N. (Norhashimah), Healey, S. (Sue), Heitz, P.U., Herzog, J. (Josef), Høgdall, E. (Estrid), Høgdall, C.K. (Claus), Hogervorst, F.B.L. (Frans), Hollestelle, A. (Antoinette), Hopper, J.L. (John), Hulick, P.J. (Peter), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Ito, H. (Hidemi), Jakubowska, A. (Anna), Janavicius, R. (Ramunas), Jensen, A. (Allan), John, E.M. (Esther), Johnson, N. (Nichola), Kabisch, M. (Maria), Kang, D. (Daehee), Kapuscinski, M.K. (Miroslav K.), Karlan, B.Y. (Beth Y.), Khan, S. (Sofia), Kiemeney, L.A.L.M. (Bart), Kjaer, M. (Michael), Knight, J.A. (Julia), Konstantopoulou, I. (I.), Kosma, V-M. (Veli-Matti), Kristensen, V. (Vessela), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Hoya, M. (Miguel) de La, Laitman, Y. (Yael), Lambrechts, D. (Diether), Le, N.D. (Nhu D.), De Leeneer, K. (Kim), Lester, K.J. (Kathryn), Levine, D.A. (Douglas), Li, J. (Jingmei), Lindblom, A. (Annika), Long, J. (Jirong), Lophatananon, A. (Artitaya), Loud, J.T. (Jennifer), Lu, K.H. (Karen), Lubinski, J. (Jan), Mannermaa, A. (Arto), Manoukian, S. (Siranoush), Le Marchand, L. (Loic), Margolin, S. (Sara), Marme, F. (Frederick), Massuger, L.F. (Leon), Matsuo, K. (Keitaro), Mazoyer, S. (Sylvie), McGuffog, L. (Lesley), McLean, C.A. (Catriona Ann), McNeish, I. (Iain), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Milne, R.L. (Roger), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Muir, K.R. (K.), Mulligan, A.-M. (Anna-Marie), Nathanson, K.L. (Katherine), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Nord, S. (Silje), Nussbaum, R.L. (Robert L.), Odunsi, K. (Kunle), Offit, K. (Kenneth), Olah, E., Olopade, O.I. (Olufunmilayo I.), Olson, J.E. (Janet), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Orlow, I. (Irene), Orr, N. (Nick), Osorio, A. (Ana), Park, S.K. (Sue Kyung), Pearce, C.L. (Celeste), Pejovic, T. (Tanja), Peterlongo, P. (Paolo), Pfeiler, G. (Georg), Phelan, C. (Catherine), Poole, E.M. (Elizabeth), Pykäs, K. (Katri), Radice, P. (Paolo), Rantala, J. (Johanna), Rashid, M.U. (Muhammad), Rennert, G. (Gad), Rhenius, V. (Valerie), Rhiem, K. (Kerstin), Risch, H. (Harvey), Rodriguez, G.C. (Gustavo), Rossing, M.A. (Mary Anne), Rudolph, A. (Anja), Salvesen, H.B. (Helga), Sangrajrang, S. (Suleeporn), Sawyer, E.J. (Elinor J.), Schildkraut, J.M. (Joellen), Schmidt, M.K. (Marjanka), Schmutzler, R.K. (Rita), Sellers, T.A. (Thomas A.), Seynaeve, C.M. (Caroline), Shah, M. (Mitul), Shen, C.-Y. (Chen-Yang), Shu, X.-O. (Xiao-Ou), Sieh, W. (Weiva), Singer, C.F. (Christian), Sinilnikova, O. (Olga), Slager, S. (Susan), Song, H. (Honglin), Soucy, P. (Penny), Southey, M.C. (Melissa), Stenmark-Askmalm, M. (Marie), Stoppa-Lyonnet, D. (Dominique), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Tchatchou, S. (Sandrine), Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn), Terry, M.B. (Mary Beth), Thomassen, M. (Mads), Tibiletti, M.G. (Maria Grazia), Tihomirova, L. (Laima), Tognazzo, S. (Silvia), Toland, A.E. (Amanda), Tomlinson, I.P. (Ian), Torres, D. (Diana), Truong, T. (Thérèse), Tseng, C.-C. (Chiu-Chen), Tung, N. (Nadine), Tworoger, S.S. (Shelley S.), Vachon, C. (Celine), Van Den Ouweland, A.M.W. (Ans M.W.), Van Doorn, H.C. (Helena C.), Rensburg, E.J. (Elizabeth) van, Veer, L.J. (Laura) van 't, Vanderstichele, A. (Adriaan), Vergote, I. (Ignace), Vijai, J. (Joseph), Wang, Q. (Qin), Wang-Gohrke, S. (Shan), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wildiers, H. (Hans), Winqvist, R. (Robert), Wu, A.H. (Anna), Yannoukakos, D. (Drakoulis), Yoon, S.-Y. (Sook-Yee), Yu, J-C. (Jyh-Cherng), Zheng, W. (Wei), Zheng, Y. (Ying), Khanna, K.K. (Kum Kum), Simard, J. (Jacques), Monteiro, A.N.A. (Alvaro N.), French, J.D. (Juliet), Couch, F.J. (Fergus), Freedman, M. (Matthew), Easton, D.F. (Douglas F.), Dunning, A.M. (Alison), Pharoah, P.D.P. (Paul), Edwards, S.L. (Stacey), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Gayther, S.A. (Simon), Bowtell, D. (David), DeFazio, A. (Anna), Webb, P. (Penny), Collonge-Rame, M.-A., Damette, A. (Alexandre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Berthet, P. (Pascaline), Vaur, D. (Dominique), Castera, L. (Laurent), Ferrer, S.F., Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Coron, F. (Fanny), Faivre, L. (Laurence), Baurand, A. (Amandine), Jacquot, C. (Caroline), Bertolone, G. (Geoffrey), Lizard, S. (Sarab), Leroux, D. (Dominique), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Adenis, C. (Claude), Vénat-Bouvet, L. (Laurence), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Calender, A. (Alain), Giraud, S. (Sophie), Verny-Pierre, C. (Carole), Lasset, C. (Christine), Bonadona, V. (Valérie), Barjhoux, L. (Laure), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Coupier, I. (Isabelle), Pujol, P. (Pascal), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Delnatte, C.D. (Capucine), Bézieau, S. (Stéphane), Mari, V. (Véronique), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Rouleau, E. (Etienne), Golmard, L. (Lisa), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Pauw, A. (Antoine) de, Elan, C. (Camille), Fourme, E. (Emmanuelle), Birot, A.-M. (Anne-Marie), Saule, C. (Claire), Laurent, M. (Maïté), Houdayer, C. (Claude), Lesueur, F. (Fabienne), Mebirouk, N. (Noura), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Warcoin, M. (Mathilde), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Mortemousque, I. (Isabelle), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Guillaud-Bataille, M. (Marine), Gregory, H. (Helen), Miedzybrodzka, Z. (Zosia), Morrison, P.J. (Patrick), Donaldson, A. (Alan), Rogers, M.T. (Mark), Kennedy, M.J. (John), Porteous, M.E. (Mary), Brady, A. (A.), Barwell, J. (Julian), Foo, C. (Claire), Lalloo, F. (Fiona), Side, L. (Lucy), Eason, J. (Jacqueline), Henderson, A. (Alex), Walker, L.J. (Lisa), Cook, J. (Jackie), Snape, K. (Katie), Murray, A. (Alexandra), McCann, E. (Emma), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Kolk, L.E. (Lizet) van der, Russell, N.S. (Nicola), Lange, J.L. (J.) de, Wijnands, R., Collée, J.M. (Margriet), Hooning, M.J. (Maartje), Seynaeve, C., Deurzen, C.H.M. (Carolien) van, Obdeijn, A.I.M. (Inge-Marie), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Pol, C. (Carmen) van der, Os, T.A.M. (Theo) van, Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Siesling, S., Verloop, J., Overbeek, L.I.H. (Lucy), Fox, S.B. (Stephen), Kirk, J. (Judy), Lindeman, G.J. (Geoffrey), and Price, M. (Melanie)
Abstract: A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
Published: 2016
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21. Recurrent candidiasis and early-onset gastric cancer in a patient with a genetically defined partial MYD88 defect

Author: Vogelaar, I.P. (Ingrid P.), Ligtenberg, M.J. (Marjolijn), Van Der Post, R.S. (Rachel S.), de Voer, R.M. (Richarda M.), Kets, C.M. (Marleen), Jansen, T.J.G. (Trees J. G.), Jacobs, L. (Liesbeth), Schreibelt, G. (Gerty), Vries, I.J.M. (Jolanda) de, Netea, M.G. (Mihai), Hoogerbrugge, N. (Nicoline), Lubinski, J. (Jan), Jakubowska, A. (Anna), Teodorczyk, U. (Urszula), Schackert, H.K. (Hans), Aalfs, C.M. (Cora), Gómez García, E.B. (Encarna), Ranzani, G.N. (Guglielmina N.), Molinaro, V. (Valeria), Hest, L.P. (Liselotte) van, Hes, F.J. (Frederik), Holinski-Feder, E. (Elke), Genuardi, M. (Maurizio), Ausems, M.G.E.M. (Margreet), Sijmons, R.H. (Rolf), Wagner, A. (Anja), Kolk, L.E. (Lizet) van der, Pinheiro, H. (Hugo), Oliveira, C. (Carla), Bjørnevoll, I. (Inga), Høberg Vetti, H. (Hildegunn), Han, J., van Krieken, J.M., Vogelaar, I.P. (Ingrid P.), Ligtenberg, M.J. (Marjolijn), Van Der Post, R.S. (Rachel S.), de Voer, R.M. (Richarda M.), Kets, C.M. (Marleen), Jansen, T.J.G. (Trees J. G.), Jacobs, L. (Liesbeth), Schreibelt, G. (Gerty), Vries, I.J.M. (Jolanda) de, Netea, M.G. (Mihai), Hoogerbrugge, N. (Nicoline), Lubinski, J. (Jan), Jakubowska, A. (Anna), Teodorczyk, U. (Urszula), Schackert, H.K. (Hans), Aalfs, C.M. (Cora), Gómez García, E.B. (Encarna), Ranzani, G.N. (Guglielmina N.), Molinaro, V. (Valeria), Hest, L.P. (Liselotte) van, Hes, F.J. (Frederik), Holinski-Feder, E. (Elke), Genuardi, M. (Maurizio), Ausems, M.G.E.M. (Margreet), Sijmons, R.H. (Rolf), Wagner, A. (Anja), Kolk, L.E. (Lizet) van der, Pinheiro, H. (Hugo), Oliveira, C. (Carla), Bjørnevoll, I. (Inga), Høberg Vetti, H. (Hildegunn), Han, J., and van Krieken, J.M.
Abstract: Gastric cancer is caused by both genetic and environmental factors. A woman who suffered from recurrent candidiasis throughout her life developed diffuse-type gastric cancer at the age of 23 years. Using whole-exome sequencing we identified a germline homozygous missense variant in MYD88. Immunological assays on peripheral blood mononuclear cells revealed an impaired immune response upon stimulation with Candida albicans, characterized by a defective production of the cytokine interleukin-17. Our data suggest that a genetic defect in MYD88 results in an impaired immune response and may increase gastric cancer risk.
Published: 2016
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22. Timing of risk reducing mastectomy in breast cancer patients carrying a BRCA1/2 mutation: retrospective data from the Dutch HEBON study

Author: Wevers, M.R., Schmidt, M.K. (Marjanka), Engelhardt, E.G., Verhoef, S., Hooning, M.J. (Maartje), Kriege, M. (Mieke), Seynaeve, C.M. (Caroline), Collée, J.M. (Margriet), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Koppert, L.B. (Linetta), Witkamp, A.J. (A.), Rutgers, E.J.T. (Emiel), Aaronson, N.K. (Neil), Rookus, M.A. (M.), Ausems, M.G.E.M. (Margreet), Wevers, M.R., Schmidt, M.K. (Marjanka), Engelhardt, E.G., Verhoef, S., Hooning, M.J. (Maartje), Kriege, M. (Mieke), Seynaeve, C.M. (Caroline), Collée, J.M. (Margriet), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Koppert, L.B. (Linetta), Witkamp, A.J. (A.), Rutgers, E.J.T. (Emiel), Aaronson, N.K. (Neil), Rookus, M.A. (M.), and Ausems, M.G.E.M. (Margreet)
Abstract: It is expected that rapid genetic counseling and testing (RGCT) will lead to increasing numbers of breast cancer (BC) patients knowing their BRCA1/2 carrier status before primary surgery. Considering the potential impact of knowing one’s status on uptake and timing of risk-reducing contralateral mastectomy (RRCM), we aimed to evaluate trends over time in RRCM, and differences between carriers identified either before (predictively) or after (diagnostically) diagnosis. We collected data from female BRCA1/2 mutation carriers diagnosed with BC between 1995 and 2009 from four Dutch university hospitals. We compared the timing of genetic testing and RRCM in relation to diagnosis in 1995–2000 versus 2001–2009 for all patients, and predictively and diagnostically tested patients separately. Of 287 patients, 219 (76 %) had a diagnostic BRCA1/2 test. In this cohort, the median time from diagnosis to DNA testing decreased from 28 months for those diagnosed between 1995 and 2000 to 14 months for those diagnosed between 2001 and 2009 (p < 0.001). Similarly, over time women in this cohort underwent RRCM sooner after diagnosis (median of 77 vs. 27 months, p = 0.05). Predictively tested women who subsequently developed BC underwent an immediate RRCM significantly more often than women who had a diagnostic test (21/61, 34 %, vs. 13/170, 7.6 %, p < 0.001). Knowledge of carrying a BRCA1/2 mutation when diagnosed with BC influenced decisions concerning primary surgery. Additionally, in more recent years, women who had not undergone predictive testing were more likely to undergo diagnostic DNA testing and RRCM sooner after diagnosis. This suggests the need for RGCT to guide treatment decisions.
Published: 2015
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23. Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer

Author: Rebbeck, R. (Timothy), Mitra, N. (Nandita), Wan, F. (Fei), Sinilnikova, O. (Olga), Healey, S. (Sue), McGuffog, L. (Lesley), Chenevix-Trench, G. (Georgia), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Nathanson, K.L. (Katherine), Laitman, Y. (Yael), Kushnir, A. (Anya), Paluch-Shimon, S. (Shani), Berger, R. (Raanan), Zidan, J. (Jamal), Friedman, E. (Eitan), Ehrencrona, H. (Hans), Stenmark-Askmalm, M. (Marie), Einbeigi, Z. (Zakaria), Loman, N. (Niklas), Harbst, K. (Katja), Rantala, J. (Johanna), Melin, B. (Beatrice), Huo, D. (Dezheng), Olopade, O.I. (Olofunmilayo), Seldon, J.L. (Joyce), Ganz, P.A. (Patricia), Nussbaum, R.L. (Robert L.), Chan, S. (Salina), Odunsi, K. (Kunle), Gayther, S.A. (Simon), Domchek, S.M. (Susan), Arun, B.K. (Banu), Lu, K.H. (Karen), Mitchell, G. (Gillian), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Godwin, A.K. (Andrew), Pathak, S.S., Ross, E.B. (Eric), Daly, M.J. (Mark), Whittemore, A.S. (Alice), John, E.M. (Esther), Miron, A. (Alexander), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Hansen, T.V.O. (Thomas), Ramon Y Cajal, T., Osorio, A. (Ana), Benítez, J. (Javier), Godino, J. (Javier), Tejada, M.I., Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Bobolis, K.A. (Kristie A.), Sand, S.R. (Sharon), Fontaine, A. (Annette), Savarese, A. (Antonella), Pasini, B. (Barbara), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Zaffaroni, D. (Daniela), Vignolo-Lutati, F. (Francesca), Scuvera, G. (Giulietta), Giannini, G. (Giuseppe), Bernard, L. (Loris), Genuardi, M. (Maurizio), Radice, P. (Paolo), Dolcetti, R. (Riccardo), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Gismondi, V. (Viviana), Yannoukakos, D. (Drakoulis), Fostira, F. (Florentia), Garber, J. (Judy), Torres, D. (Diana), Rashid, M.U. (Muhammad), Hamann, U. (Ute), Peock, S. (Susan), Frost, D. (Debra), Platte, R. (Radka), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T. (Trevor), Cook, J. (Jackie), Brewer, C. (Carole), Hodgson, S. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Izatt, L. (Louise), Adlard, L., Donaldson, A. (Alan), Ellis, S.D. (Steve), Sharma, P. (Priyanka), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Becker, A. (Alexandra), Rhiem, K. (Kerstin), Hahnen, E. (Eric), Engel, C. (Christoph), Meindl, A. (Alfons), Engert, S. (Stefanie), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Mundhenke, C. (Christoph), Niederacher, D. (Dieter), Fleisch, M.C. (Markus), Sutter, C. (Christian), Bartram, C.R. (Claus), Dikow, N. (Nicola), Wang-Gohrke, S. (Shan), Gadzicki, D. (Dorothea), Steinemann, D. (Doris), Kast, K. (Karin), Beer, M. (Marit), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Weber, B.H.F. (Bernhard), Stoppa-Lyonnet, D. (Dominique), Belotti, M. (Muriel), Gauthier-Villars, M. (Marion), Damiola, F. (Francesca), Boutry-Kryza, N. (N.), Lasset, C. (Christine), Sobol, H. (Hagay), Peyrat, J.-P., Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Collonge-Rame, M.-A., Mortemousque, I. (Isabelle), Nogues, C. (Catherine), Rouleau, E. (Etienne), Isaacs, C. (Claudine), Paepe, A. (Anne) de, Poppe, B. (Bruce), Claes, K. (Kathleen), De Leeneer, K. (Kim), Piedmonte, M. (Marion), Rodriguez, G. (Gustavo), Wakely, K. (Katie), Boggess, J.F. (John), Blank, S.V. (Stephanie), Basil, J. (Jack), Azodi, M. (Masoud), Phillips, K.-A. (Kelly-Anne), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Romero, A. (Atocha), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Hout, A.H. (Annemarie) van der, Hogervorst, F.B.L. (Frans), Verhoef, S., Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Oosterwijk, J.C. (Jan), Gille, J.J. (Johan), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Devilee, P. (Peter), Mensenkamp, A.R. (Arjen), Kwong, A. (Ava), Olah, E., Papp, J. (Janos), Díez, O. (Orland), Lázaro, C. (Conxi), Darder, E. (Esther), Blanco, I. (Ignacio), Salinas, M., Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Sukiennicki, G. (Grzegorz), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Cybulski, C. (Cezary), Toloczko-Grabarek, A. (Aleksandra), Złowocka-Perłowska, E. (Elzbieta), Menkiszak, J. (Janusz), Arason, A. (Adalgeir), Barkardottir, R.B. (Rosa), Simard, J. (Jacques), Laframboise, R. (Rachel), Montagna, M. (Marco), Agata, S. (Simona), Alducci, E. (Elisa), Peixoto, A. (Ana), Teixeira, P.J., Spurdle, A.B. (Amanda), Lee, M.H. (Min Hyuk), Park, S.K. (Sue), Kim, S.-W. (Sung-Won), Friebel, M.O.W. (Mark ), Couch, F.J. (Fergus), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Guidugli, L. (Lucia), Wang, X. (Xianshu), Tischkowitz, M. (Marc), Foretova, L. (Lenka), Vijai, J. (Joseph), Offit, K. (Kenneth), Robson, M. (Mark), Rau-Murthy, R. (Rohini), Kauff, N. (Noah), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Berger, A. (Andreas), Greene, M.H. (Mark), Mai, P.L. (Phuong), Imyanitov, E.N. (Evgeny), Toland, A.E. (Amanda), Senter, L. (Leigha), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Skytte, A.-B. (Anne-Bine), Sunde, L. (Lone), Thomassen, M. (Mads), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Caligo, M.A. (Maria), Aretini, P. (Paolo), Teo, S.-H. (Soo-Hwang), Selkirk, C.G. (Christina), Hulick, P.J. (Peter), Andrulis, I.L. (Irene), Rebbeck, R. (Timothy), Mitra, N. (Nandita), Wan, F. (Fei), Sinilnikova, O. (Olga), Healey, S. (Sue), McGuffog, L. (Lesley), Chenevix-Trench, G. (Georgia), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Nathanson, K.L. (Katherine), Laitman, Y. (Yael), Kushnir, A. (Anya), Paluch-Shimon, S. (Shani), Berger, R. (Raanan), Zidan, J. (Jamal), Friedman, E. (Eitan), Ehrencrona, H. (Hans), Stenmark-Askmalm, M. (Marie), Einbeigi, Z. (Zakaria), Loman, N. (Niklas), Harbst, K. (Katja), Rantala, J. (Johanna), Melin, B. (Beatrice), Huo, D. (Dezheng), Olopade, O.I. (Olofunmilayo), Seldon, J.L. (Joyce), Ganz, P.A. (Patricia), Nussbaum, R.L. (Robert L.), Chan, S. (Salina), Odunsi, K. (Kunle), Gayther, S.A. (Simon), Domchek, S.M. (Susan), Arun, B.K. (Banu), Lu, K.H. (Karen), Mitchell, G. (Gillian), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Godwin, A.K. (Andrew), Pathak, S.S., Ross, E.B. (Eric), Daly, M.J. (Mark), Whittemore, A.S. (Alice), John, E.M. (Esther), Miron, A. (Alexander), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Tihomirova, L. (Laima), Tung, N. (Nadine), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Steele, L. (Linda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Ejlertsen, B. (Bent), Gerdes, A-M. (Anne-Marie), Hansen, T.V.O. (Thomas), Ramon Y Cajal, T., Osorio, A. (Ana), Benítez, J. (Javier), Godino, J. (Javier), Tejada, M.I., Duran, M. (Mercedes), Weitzel, J.N. (Jeffrey), Bobolis, K.A. (Kristie A.), Sand, S.R. (Sharon), Fontaine, A. (Annette), Savarese, A. (Antonella), Pasini, B. (Barbara), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Zaffaroni, D. (Daniela), Vignolo-Lutati, F. (Francesca), Scuvera, G. (Giulietta), Giannini, G. (Giuseppe), Bernard, L. (Loris), Genuardi, M. (Maurizio), Radice, P. (Paolo), Dolcetti, R. (Riccardo), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Gismondi, V. (Viviana), Yannoukakos, D. (Drakoulis), Fostira, F. (Florentia), Garber, J. (Judy), Torres, D. (Diana), Rashid, M.U. (Muhammad), Hamann, U. (Ute), Peock, S. (Susan), Frost, D. (Debra), Platte, R. (Radka), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T. (Trevor), Cook, J. (Jackie), Brewer, C. (Carole), Hodgson, S. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Izatt, L. (Louise), Adlard, L., Donaldson, A. (Alan), Ellis, S.D. (Steve), Sharma, P. (Priyanka), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Becker, A. (Alexandra), Rhiem, K. (Kerstin), Hahnen, E. (Eric), Engel, C. (Christoph), Meindl, A. (Alfons), Engert, S. (Stefanie), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Mundhenke, C. (Christoph), Niederacher, D. (Dieter), Fleisch, M.C. (Markus), Sutter, C. (Christian), Bartram, C.R. (Claus), Dikow, N. (Nicola), Wang-Gohrke, S. (Shan), Gadzicki, D. (Dorothea), Steinemann, D. (Doris), Kast, K. (Karin), Beer, M. (Marit), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Weber, B.H.F. (Bernhard), Stoppa-Lyonnet, D. (Dominique), Belotti, M. (Muriel), Gauthier-Villars, M. (Marion), Damiola, F. (Francesca), Boutry-Kryza, N. (N.), Lasset, C. (Christine), Sobol, H. (Hagay), Peyrat, J.-P., Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Collonge-Rame, M.-A., Mortemousque, I. (Isabelle), Nogues, C. (Catherine), Rouleau, E. (Etienne), Isaacs, C. (Claudine), Paepe, A. (Anne) de, Poppe, B. (Bruce), Claes, K. (Kathleen), De Leeneer, K. (Kim), Piedmonte, M. (Marion), Rodriguez, G. (Gustavo), Wakely, K. (Katie), Boggess, J.F. (John), Blank, S.V. (Stephanie), Basil, J. (Jack), Azodi, M. (Masoud), Phillips, K.-A. (Kelly-Anne), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Romero, A. (Atocha), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Hout, A.H. (Annemarie) van der, Hogervorst, F.B.L. (Frans), Verhoef, S., Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Oosterwijk, J.C. (Jan), Gille, J.J. (Johan), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Kets, C.M. (Marleen), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Devilee, P. (Peter), Mensenkamp, A.R. (Arjen), Kwong, A. (Ava), Olah, E., Papp, J. (Janos), Díez, O. (Orland), Lázaro, C. (Conxi), Darder, E. (Esther), Blanco, I. (Ignacio), Salinas, M., Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Jaworska-Bieniek, K. (Katarzyna), Durda, K. (Katarzyna), Sukiennicki, G. (Grzegorz), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Cybulski, C. (Cezary), Toloczko-Grabarek, A. (Aleksandra), Złowocka-Perłowska, E. (Elzbieta), Menkiszak, J. (Janusz), Arason, A. (Adalgeir), Barkardottir, R.B. (Rosa), Simard, J. (Jacques), Laframboise, R. (Rachel), Montagna, M. (Marco), Agata, S. (Simona), Alducci, E. (Elisa), Peixoto, A. (Ana), Teixeira, P.J., Spurdle, A.B. (Amanda), Lee, M.H. (Min Hyuk), Park, S.K. (Sue), Kim, S.-W. (Sung-Won), Friebel, M.O.W. (Mark ), Couch, F.J. (Fergus), Lindor, N.M. (Noralane), Pankratz, V.S. (Shane), Guidugli, L. (Lucia), Wang, X. (Xianshu), Tischkowitz, M. (Marc), Foretova, L. (Lenka), Vijai, J. (Joseph), Offit, K. (Kenneth), Robson, M. (Mark), Rau-Murthy, R. (Rohini), Kauff, N. (Noah), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Berger, A. (Andreas), Greene, M.H. (Mark), Mai, P.L. (Phuong), Imyanitov, E.N. (Evgeny), Toland, A.E. (Amanda), Senter, L. (Leigha), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Skytte, A.-B. (Anne-Bine), Sunde, L. (Lone), Thomassen, M. (Mads), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Caligo, M.A. (Maria), Aretini, P. (Paolo), Teo, S.-H. (Soo-Hwang), Selkirk, C.G. (Christina), Hulick, P.J. (Peter), and Andrulis, I.L. (Irene)
Abstract: Importance: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. Objective: To identify mutation-specific cancer risks for carriers of BRCA1/2. Design, Setting, and Participants: Observational study ofwomen whowere ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents.We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position.We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. Exposures: Mutations of BRCA1 or BRCA2. Main Outcomes and Measures: Breast and ovarian cancer risks. Results: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95%CI, 1.22-1.74; P = 2 × 10-6), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95%CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95%CI, 1.22-1.55; P = 6 × 10-9).We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95%CI, 0.56-0.70; P = 9 × 10-17). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95%CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95%CI, 1.10-2.40; P = .01), and c.7394 to
Published: 2015
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24. Repeated nipple fluid aspiration

Author: De Groot, J.S. (J. S.), Moelans, C.B. (Cathy), Elias, S.G. (S. G.), Hennink, A. (A.), Verolme, B. (B.), Suijkerbuijk, K.P.M. (K. P M), Jager, A. (Agnes), Seynaeve, C.M. (Caroline), Bos, P.K. (Koen), Witkamp, A.J. (A.), Ausems, M.G.E.M. (Margreet), Diest, P.J. (Paul) van, Wall, E. (Elsken) van der, De Groot, J.S. (J. S.), Moelans, C.B. (Cathy), Elias, S.G. (S. G.), Hennink, A. (A.), Verolme, B. (B.), Suijkerbuijk, K.P.M. (K. P M), Jager, A. (Agnes), Seynaeve, C.M. (Caroline), Bos, P.K. (Koen), Witkamp, A.J. (A.), Ausems, M.G.E.M. (Margreet), Diest, P.J. (Paul) van, and Wall, E. (Elsken) van der
Abstract: Background: Despite intensive surveillance, a high rate of interval malignancies is still seen in women at increased breast cancer risk. Therefore, novel screening modalities aiming at early detection remain needed. The intraductal approach offers the possibility to directly sample fluid containing cells, DNA and proteins from the mammary ductal system where, in the majority of cases, breast cancer originates. Fluid from the breast can non-invasively be obtained by oxytocin-assisted vacuum aspiration, called nipple fluid aspiration (NFA). The goal of this feasibility study was to evaluate the potential of repeated NFA, which is a critical and essential step to evaluate its possible value as a breast cancer screening method. Methods: In this multicenter, prospective study, we annually collected nipple fluid for up to 5 consecutive years from women at increased breast cancer risk, and performed a questionnaire-based survey regarding discomfort of the aspiration. Endpoints of the current interim analyses were the feasibility and results of 994 NFA procedures in 451 women with total follow-up of 560 person years of observation. Results: In this large group of women at increased risk of breast cancer, repetitive NFA appeared to be feasible and safe. In 66.4% of aspirated breasts, nipple fluid was successfully obtained. Independent predictive factors for successful NFA were premenopausal status, spontaneous nipple discharge, smaller breast size, bilateral oophorectomy and previous use of hormone replacement therapy or anti-hormonal treatment. The procedure was well tolerated with low discomfort. Drop-out rate was 20%, which was mainly due to repeated unsuccessful aspiration attempts. Only 1.6% of women prematurely declined further participation because of side effects. Conclusions: Repeated NFA in women at increased breast cancer risk is feasible and safe. Therefore, NFA is a promising method to non-invasively obtain a valuable source of potential breast cancer specific b
Published: 2015
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25. Candidate genetic modifiers for breast and ovarian cancer risk inBRCA1andBRCA2 mutation carriers

Author: Peterlongo, P. (Paolo), Chang-Claude, J. (Jenny), Moysich, K.B. (Kirsten), Rudolph, A. (Anja), Schmutzler, R.K. (Rita), Simard, J. (Jacques), Soucy, P. (Penny), Eeles, R. (Rosalind), Easton, D.F. (Douglas), Hamann, U. (Ute), Wilkening, S. (Stefan), Chen, B. (Bowang), Rookus, M.A. (Matti), Schmidt, M.K. (Marjanka), Baan, F.H. (Frederieke) van der, Spurdle, A.B. (Amanda), Walker, L.C. (Logan), Lose, F. (Felicity), Maia, A.-T. (Ana-Teresa), Montagna, M. (Marco), Matricardi, L. (Laura), Lubinski, J. (Jan), Jakubowska, A. (Anna), Garcia, E.B.G., Olopade, O.I. (Olofunmilayo), Nussbaum, R.L. (Robert L.), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Arun, B.K. (Banu), Karlan, B.Y. (Beth), Orsulic, S. (Sandra), Lester, K.J. (Kathryn), Chung, W.K. (Wendy K.), Miron, A. (Alexander), Southey, M.C. (Melissa), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Ding, Y.C. (Yuan Chun), Neuhausen, S.L. (Susan), Hansen, T.V.O. (Thomas), Gerdes, A.-M. (Anne-Marie), Ejlertsen, B. (Bent), Jønson, L. (Lars), Osorio, A. (Ana), Martínez-Bouzas, C. (Cristina), Benítez, J. (Javier), Conway, E.E. (Edye E.), Blazer, K.R. (Kathleen R.), Weitzel, J.N. (Jeffrey), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (Daniela), Scuvera, G. (Giulietta), Barile, M. (Monica), Ficarazzi, F. (Filomena), Mariette, F. (F.), Fortuzzi, S. (S.), Viel, A. (Alessandra), Giannini, G. (Giuseppe), Papi, L. (Laura), Martayan, A. (Aline), Tibiletti, M.G. (Maria Grazia), Radice, P. (Paolo), Vratimos, A. (Athanassios), Fostira, F. (Florentia), Garber, J. (Judy), Donaldson, A. (Alan), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Brady, A. (A.), Cook, J. (Jackie), Tischkowitz, M. (Marc), Adlard, L., Barwell, J. (Julian), Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Ellis, S.D. (Steve), Cole, T. (Trevor), Godwin, A.K. (Andrew), Claes, K.B.M. (Kathleen B.M.), Van Maerken, T. (Tom), Meindl, A. (Alfons), Gehrig, P.A. (Paola A.), Sutter, C. (Christian), Engel, C. (Christoph), Niederacher, D. (Dieter), Steinemann, D. (Doris), Plendl, H. (Hansjoerg), Kast, K. (Karin), Rhiem, K. (Kerstin), Ditsch, N. (Nina), Arnold, N. (Norbert), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Wang-Gohrke, S. (Shan), Bressac-de Paillerets, B. (Brigitte), Buecher, B. (Bruno), Delnatte, C.D. (Capucine), Houdayer, C. (Claude), Stoppa-Lyonnet, D. (Dominique), Damiola, F. (Francesca), Coupier, I. (Isabelle), Barjhoux, L. (Laure), Vénat-Bouvet, L. (Laurence), Golmard, L. (Lisa), Boutry-Kryza, N. (N.), Sinilnikova, O. (Olga), Caron, O. (Olivier), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Belotti, M. (Muriel), Piedmonte, M. (Marion), Friedlander, M.L. (Michael L.), Rodriguez, G. (Gustavo), Copeland, L.J. (Larry J.), Hoya, M. (Miguel) de La, Perez-Segura, P. (Pedro), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Os, T.A.M. (Theo) van, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Vreeswijk, M.P. (Maaike), Hoogerbrugge, N. (Nicoline), Ausems, M.G.E.M. (Margreet), Doorn, H.C. (Lena) van, Collée, J.M. (Margriet), Olah, E., Díez, O. (Orland), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Brunet, J. (Joan), Feliubadaló, L. (L.), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Sukiennicki, G. (Grzegorz), Arason, A. (Adalgeir), Chiquette, J. (Jocelyne), Teixeira, P.J., Olswold, C. (Curtis), Couch, F.J. (Fergus), Lindor, N.M. (Noralane), Wang, X. (X.), Szabo, C. (Csilla), Offit, K. (Kenneth), Corines, M. (Marina), Jacobs, L. (Lauren), Robson, M.E. (Mark E.), Zhang, L. (Lingling), Joseph, V. (Vijai), Berger, A. (Andreas), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Phelan, C. (Catherine), Greene, M.H. (Mark), Mai, P.L. (Phuong), Rennert, G. (Gad), Mulligan, A.-M. (Anna-Marie), Glendon, G. (Gord), Tchatchou, S. (Sandrine), Andrulis, I.L. (Irene), Toland, A.E. (Amanda), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Thomassen, M. (Mads), Jensen, U.B., Laitman, Y. (Yael), Rantala, J. (Johanna), Wachenfeldt, A. (Anna) von, Ehrencrona, H. (Hans), Askmalm, M.S. (Marie), Borg, Å. (Åke), Kuchenbaecker, K.B. (Karoline), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Healey, S. (Sue), Lee, A. (Andrew), Pharoah, P.D.P. (Paul D.P.), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Friedman, E. (Eitan), Peterlongo, P. (Paolo), Chang-Claude, J. (Jenny), Moysich, K.B. (Kirsten), Rudolph, A. (Anja), Schmutzler, R.K. (Rita), Simard, J. (Jacques), Soucy, P. (Penny), Eeles, R. (Rosalind), Easton, D.F. (Douglas), Hamann, U. (Ute), Wilkening, S. (Stefan), Chen, B. (Bowang), Rookus, M.A. (Matti), Schmidt, M.K. (Marjanka), Baan, F.H. (Frederieke) van der, Spurdle, A.B. (Amanda), Walker, L.C. (Logan), Lose, F. (Felicity), Maia, A.-T. (Ana-Teresa), Montagna, M. (Marco), Matricardi, L. (Laura), Lubinski, J. (Jan), Jakubowska, A. (Anna), Garcia, E.B.G., Olopade, O.I. (Olofunmilayo), Nussbaum, R.L. (Robert L.), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Arun, B.K. (Banu), Karlan, B.Y. (Beth), Orsulic, S. (Sandra), Lester, K.J. (Kathryn), Chung, W.K. (Wendy K.), Miron, A. (Alexander), Southey, M.C. (Melissa), Goldgar, D. (David), Buys, S.S. (Saundra), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Ding, Y.C. (Yuan Chun), Neuhausen, S.L. (Susan), Hansen, T.V.O. (Thomas), Gerdes, A.-M. (Anne-Marie), Ejlertsen, B. (Bent), Jønson, L. (Lars), Osorio, A. (Ana), Martínez-Bouzas, C. (Cristina), Benítez, J. (Javier), Conway, E.E. (Edye E.), Blazer, K.R. (Kathleen R.), Weitzel, J.N. (Jeffrey), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (Daniela), Scuvera, G. (Giulietta), Barile, M. (Monica), Ficarazzi, F. (Filomena), Mariette, F. (F.), Fortuzzi, S. (S.), Viel, A. (Alessandra), Giannini, G. (Giuseppe), Papi, L. (Laura), Martayan, A. (Aline), Tibiletti, M.G. (Maria Grazia), Radice, P. (Paolo), Vratimos, A. (Athanassios), Fostira, F. (Florentia), Garber, J. (Judy), Donaldson, A. (Alan), Brewer, C. (Carole), Foo, C. (Claire), Evans, D.G. (Gareth), Frost, D. (Debra), Eccles, D. (Diana), Brady, A. (A.), Cook, J. (Jackie), Tischkowitz, M. (Marc), Adlard, L., Barwell, J. (Julian), Walker, L.J. (Lisa), Izatt, L. (Louise), Side, L. (Lucy), Kennedy, M.J. (John), Rogers, M.T. (Mark), Porteous, M.E. (Mary), Morrison, P.J. (Patrick), Platte, R. (Radka), Davidson, R. (Rosemarie), Hodgson, S. (Shirley), Ellis, S.D. (Steve), Cole, T. (Trevor), Godwin, A.K. (Andrew), Claes, K.B.M. (Kathleen B.M.), Van Maerken, T. (Tom), Meindl, A. (Alfons), Gehrig, P.A. (Paola A.), Sutter, C. (Christian), Engel, C. (Christoph), Niederacher, D. (Dieter), Steinemann, D. (Doris), Plendl, H. (Hansjoerg), Kast, K. (Karin), Rhiem, K. (Kerstin), Ditsch, N. (Nina), Arnold, N. (Norbert), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Wang-Gohrke, S. (Shan), Bressac-de Paillerets, B. (Brigitte), Buecher, B. (Bruno), Delnatte, C.D. (Capucine), Houdayer, C. (Claude), Stoppa-Lyonnet, D. (Dominique), Damiola, F. (Francesca), Coupier, I. (Isabelle), Barjhoux, L. (Laure), Vénat-Bouvet, L. (Laurence), Golmard, L. (Lisa), Boutry-Kryza, N. (N.), Sinilnikova, O. (Olga), Caron, O. (Olivier), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Belotti, M. (Muriel), Piedmonte, M. (Marion), Friedlander, M.L. (Michael L.), Rodriguez, G. (Gustavo), Copeland, L.J. (Larry J.), Hoya, M. (Miguel) de La, Perez-Segura, P. (Pedro), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Os, T.A.M. (Theo) van, Meijers-Heijboer, E.J. (Hanne), Hout, A.H. (Annemarie) van der, Vreeswijk, M.P. (Maaike), Hoogerbrugge, N. (Nicoline), Ausems, M.G.E.M. (Margreet), Doorn, H.C. (Lena) van, Collée, J.M. (Margriet), Olah, E., Díez, O. (Orland), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Brunet, J. (Joan), Feliubadaló, L. (L.), Cybulski, C. (Cezary), Gronwald, J. (Jacek), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Sukiennicki, G. (Grzegorz), Arason, A. (Adalgeir), Chiquette, J. (Jocelyne), Teixeira, P.J., Olswold, C. (Curtis), Couch, F.J. (Fergus), Lindor, N.M. (Noralane), Wang, X. (X.), Szabo, C. (Csilla), Offit, K. (Kenneth), Corines, M. (Marina), Jacobs, L. (Lauren), Robson, M.E. (Mark E.), Zhang, L. (Lingling), Joseph, V. (Vijai), Berger, A. (Andreas), Singer, C.F. (Christian), Rappaport, C. (Christine), Kaulich, D.G. (Daphne Gschwantler), Pfeiler, G. (Georg), Tea, M.-K., Phelan, C. (Catherine), Greene, M.H. (Mark), Mai, P.L. (Phuong), Rennert, G. (Gad), Mulligan, A.-M. (Anna-Marie), Glendon, G. (Gord), Tchatchou, S. (Sandrine), Andrulis, I.L. (Irene), Toland, A.E. (Amanda), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Thomassen, M. (Mads), Jensen, U.B., Laitman, Y. (Yael), Rantala, J. (Johanna), Wachenfeldt, A. (Anna) von, Ehrencrona, H. (Hans), Askmalm, M.S. (Marie), Borg, Å. (Åke), Kuchenbaecker, K.B. (Karoline), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Healey, S. (Sue), Lee, A. (Andrew), Pharoah, P.D.P. (Paul D.P.), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), and Friedman, E. (Eitan)
Abstract: Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants inmany candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysiswas performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.
Published: 2015
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26. Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations

Author: Brohet, R.M. (Richard), Velthuizen, S.J.C.M. (Sandra), Hogervorst, F.B.L. (Frans), Meijers-Heijboer, E.J. (Hanne), Seynaeve, C.M. (Caroline), Collée, J.M. (Margriet), Verhoef, S., Ausems, M.G.E.M. (Margreet), Hoogerbrugge, N. (Nicoline), Asperen, C.J. (Christi) van, Garcia, E.B.G., Menko, F. (Fred), Oosterwijk, J.C. (Jan), Devilee, P. (Peter), Veer, L.J. (Laura) van 't, Leeuwen, F.E. (Flora) van, Easton, D.F. (Douglas), Rookus, M.A. (M.), Antoniou, A.C. (Antonis), Rookus, M.A. (Matti), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Deurzen, C.H.M. (Carolien) van, Wijnen, J.T. (Juul), Tollenaar, R.A.E.M. (Rob), Devilee, P. (P.), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkam, A.R. (A.), Luij, R.B. (R.) van der, Aalfs, C.M. (Cora), Os, T.A.M. (Theo) van, Gille, J.J. (Johan), Waisfisz, Q. (Quinten), Gómez García, E.B. (Encarna), Blok, M.J. (Marinus), Hout, A.H. (Annemarie) van der, Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Brohet, R.M. (Richard), Velthuizen, S.J.C.M. (Sandra), Hogervorst, F.B.L. (Frans), Meijers-Heijboer, E.J. (Hanne), Seynaeve, C.M. (Caroline), Collée, J.M. (Margriet), Verhoef, S., Ausems, M.G.E.M. (Margreet), Hoogerbrugge, N. (Nicoline), Asperen, C.J. (Christi) van, Garcia, E.B.G., Menko, F. (Fred), Oosterwijk, J.C. (Jan), Devilee, P. (Peter), Veer, L.J. (Laura) van 't, Leeuwen, F.E. (Flora) van, Easton, D.F. (Douglas), Rookus, M.A. (M.), Antoniou, A.C. (Antonis), Rookus, M.A. (Matti), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Deurzen, C.H.M. (Carolien) van, Wijnen, J.T. (Juul), Tollenaar, R.A.E.M. (Rob), Devilee, P. (P.), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkam, A.R. (A.), Luij, R.B. (R.) van der, Aalfs, C.M. (Cora), Os, T.A.M. (Theo) van, Gille, J.J. (Johan), Waisfisz, Q. (Quinten), Gómez García, E.B. (Encarna), Blok, M.J. (Marinus), Hout, A.H. (Annemarie) van der, Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, and Vasen, H. (Hans)
Abstract: Background: BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. Methods: We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a modified segregation analysis model. Results: The average cumulative breast cancer risk by age 70 years was estimated to be 45% (95% CI 36 to 52%) for BRCA1 and 27% (95% CI 14 to 38%) for BRCA2 mutation carriers. The corresponding cumulative risks for ovarian cancer were 31% (95% CI 17 to 43%) for BRCA1 and 6% (95% CI 2 to 11%) for BRCA2 mutation carriers. In BRCA1 families, breast cancer relative risk (RR) increased with more recent birth cohort (pheterogeneity = 0.0006) and stronger family histories of breast cancer (pheterogeneity<0.001). For BRCA1, our data suggest a significant association between the location of the mutation and the ratio of breast to ovarian cancer (p<0.001). By contrast, in BRCA2 families, no evidence was found for risk heterogeneity by birth cohort, family history or mutation location. Conclusions: BRCA1 mutation carriers conferred lower overall breast and ovarian cancer risks than reported so far, while the estimates of BRCA2 mutations were among the lowest. The low estimates for BRCA1 might be due to older birth cohorts, a moderate family history
Published: 2014
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27. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: Results from the initial screening round of the IMPACT study

Author: Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Castro, E. (Elena), Lilja, H. (Hans), Vickers, A.J. (Andrew), Sjoberg, D. (Daniel), Assel, M. (Matthias), Foster, C.S. (Christopher), Mitchell, G. (Gillian), Drew, K. (Kate), Maehle, L., Axcrona, K., Evans, D.G. (Gareth), Bulman, B., Eccles, D. (Diana), McBride, D. (Donna), Asperen, C.J. (Christi) van, Vasen, H. (Hans), Kiemeney, L.A.L.M. (Bart), Ringelberg, J. (Janneke), Cybulski, C. (Cezary), Wokolorczyk, D. (Dominika), Selkirk, C.G. (Christina), Hulick, P.J. (Peter), Bojesen, S.E. (Stig), Skytte, A.-B. (Anne-Bine), Lam, J. (Jimmy), Taylor, L. (Lorne), Oldenburg, R.A. (Rogier), Cremers, R.G.H.M. (Ruben), Verhaegh, G. (Gerald), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Blanco, I. (Ignacio), Salinas, M., Cook, J. (Jackie), Rosario, K. (Karyna), Buys, S.S. (Saundra), Conner, T. (Tom), Ausems, M.G.E.M. (Margreet), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Domchek, S.M. (Susan), Powers, J. (Jacquelyn), Teixeira, P.J., Maia, S. (Sofia), Foulkes, W.D. (William), Taherian, N. (Nassim), Ruijs, M.W.G. (Marielle), Enden, A.T.H.-V. (Apollonia T. Helderman-Van) den, Izatt, L. (Louise), Davidson, R. (Rosemarie), Adank, M.A. (Muriel), Walker, L.J. (Lisa), Schmutzler, R.K. (Rita), Tucker, K. (Kathryn), Kirk, J. (Judy), Hodgson, S.V. (Shirley), Harris, M. (Marion), Douglas, F. (Fiona), Lindeman, G.J. (Geoffrey), Zgajnar, J. (Janez), Tischkowitz, M. (Marc), Clowes, V., Susman, R. (Rachel), Ramon Y Cajal, T., Patcher, N. (Nicholas), Gadea, N. (Neus), Spigelman, A., Os, T.A.M. (Theo) van, Liljegren, A. (Annelie), Side, L. (Lucy), Brewer, C. (Carole), Brady, A.F. (Angela), Donaldson, A. (Alan), Stefansdottir, V. (Vigdis), Friedman, E. (Eitan), Chen-Shtoyerman, R. (Rakefet), Amor, D. (David), Copakova, L. (Lucia), Barwell, J. (Julian), Giri, V.N. (Veda), Murthy, A.C. (Adeline C.), Nicolai, N. (Nicola), Teo, S.-H. (Soo-Hwang), Greenhalgh, T. (Trisha), Strom, S., Henderson, A. (Alex), McGrath, J. (John), Gallagher, D. (David), Aaronson, N.K. (Neil), Ardern-Jones, A. (Audrey), Bangma, C.H. (Chris), Dearnaley, D. (David), Costello, A. (Anthony), Eyfjord, J., Rothwell, J. (Jeanette), Falconer, A., Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johannson, O.T. (Oskar), Khoo, V., Kote-Jarai, Z., Lubinski, J. (Jan), Melia, J., McKinley, E.T. (Enid), Mitra, A. (Anita), Moynihan, C., Rennert, G. (Gad), Suri, M. (Mohnish), Wilson, P., Killick, S.R., Moss, S.M. (Sue), Eeles, R. (Rosalind), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Castro, E. (Elena), Lilja, H. (Hans), Vickers, A.J. (Andrew), Sjoberg, D. (Daniel), Assel, M. (Matthias), Foster, C.S. (Christopher), Mitchell, G. (Gillian), Drew, K. (Kate), Maehle, L., Axcrona, K., Evans, D.G. (Gareth), Bulman, B., Eccles, D. (Diana), McBride, D. (Donna), Asperen, C.J. (Christi) van, Vasen, H. (Hans), Kiemeney, L.A.L.M. (Bart), Ringelberg, J. (Janneke), Cybulski, C. (Cezary), Wokolorczyk, D. (Dominika), Selkirk, C.G. (Christina), Hulick, P.J. (Peter), Bojesen, S.E. (Stig), Skytte, A.-B. (Anne-Bine), Lam, J. (Jimmy), Taylor, L. (Lorne), Oldenburg, R.A. (Rogier), Cremers, R.G.H.M. (Ruben), Verhaegh, G. (Gerald), Zelst-Stams, W.A. van, Oosterwijk, J.C. (Jan), Blanco, I. (Ignacio), Salinas, M., Cook, J. (Jackie), Rosario, K. (Karyna), Buys, S.S. (Saundra), Conner, T. (Tom), Ausems, M.G.E.M. (Margreet), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Domchek, S.M. (Susan), Powers, J. (Jacquelyn), Teixeira, P.J., Maia, S. (Sofia), Foulkes, W.D. (William), Taherian, N. (Nassim), Ruijs, M.W.G. (Marielle), Enden, A.T.H.-V. (Apollonia T. Helderman-Van) den, Izatt, L. (Louise), Davidson, R. (Rosemarie), Adank, M.A. (Muriel), Walker, L.J. (Lisa), Schmutzler, R.K. (Rita), Tucker, K. (Kathryn), Kirk, J. (Judy), Hodgson, S.V. (Shirley), Harris, M. (Marion), Douglas, F. (Fiona), Lindeman, G.J. (Geoffrey), Zgajnar, J. (Janez), Tischkowitz, M. (Marc), Clowes, V., Susman, R. (Rachel), Ramon Y Cajal, T., Patcher, N. (Nicholas), Gadea, N. (Neus), Spigelman, A., Os, T.A.M. (Theo) van, Liljegren, A. (Annelie), Side, L. (Lucy), Brewer, C. (Carole), Brady, A.F. (Angela), Donaldson, A. (Alan), Stefansdottir, V. (Vigdis), Friedman, E. (Eitan), Chen-Shtoyerman, R. (Rakefet), Amor, D. (David), Copakova, L. (Lucia), Barwell, J. (Julian), Giri, V.N. (Veda), Murthy, A.C. (Adeline C.), Nicolai, N. (Nicola), Teo, S.-H. (Soo-Hwang), Greenhalgh, T. (Trisha), Strom, S., Henderson, A. (Alex), McGrath, J. (John), Gallagher, D. (David), Aaronson, N.K. (Neil), Ardern-Jones, A. (Audrey), Bangma, C.H. (Chris), Dearnaley, D. (David), Costello, A. (Anthony), Eyfjord, J., Rothwell, J. (Jeanette), Falconer, A., Grönberg, H. (Henrik), Hamdy, F. (Freddie), Johannson, O.T. (Oskar), Khoo, V., Kote-Jarai, Z., Lubinski, J. (Jan), Melia, J., McKinley, E.T. (Enid), Mitra, A. (Anita), Moynihan, C., Rennert, G. (Gad), Suri, M. (Mohnish), Wilson, P., Killick, S.R., Moss, S.M. (Sue), and Eeles, R. (Rosalind)
Abstract: Background Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations. Objective To report the first year's screening results for all men at enrolment in the study. Design, setting and participants We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrolment, and those men with PSA >3 ng/ml were offered prostate biopsy. Outcome measurements and statistical analysis PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types. Results and limitations We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high
Published: 2014
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28. Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

Author: Couch, F.J. (Fergus), McGuffog, L. (Lesley), Lee, A. (Andrew), Olswold, C. (Curtis), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Fredericksen, Z. (Zachary), Barrowdale, D. (Daniel), Dennis, J. (Joe), Gaudet, M.M. (Mia), Dicks, E. (Ed), Kosel, M. (Matthew), Healey, S. (Sue), Sinilnikova, O. (Olga), Bacot, F. (Francois), Vincent, D. (Daniel), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Jakubowska, A. (Anna), Radice, P. (Paolo), Schmutzler, R.K. (Rita), Domchek, S.M. (Susan), Piedmonte, M. (Marion), Singer, C.F. (Christian), Friedman, E. (Eitan), Thomassen, M. (Mads), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Szabo, C. (Csilla), Blanco, I. (Ignacio), Greene, M.H. (Mark), Karlan, B.Y. (Beth), Garber, J., Phelan, C. (Catherine), Weitzel, J.N. (Jeffrey), Montagna, M. (Marco), Olah, E., Andrulis, I.L. (Irene), Godwin, A.K. (Andrew), Yannoukakos, D. (Drakoulis), Goldgar, D. (David), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Terry, M.-B. (Mary-Beth), Daly, M.B. (Mary), Rensburg, E.J. (Elizabeth) van, Hamann, U. (Ute), Ramus, S.J. (Susan), Ewart-Toland, A. (Amanda), Caligo, M.A. (Maria), Olopade, O.I. (Olofunmilayo), Tung, N. (Nadine), Claes, K. (Kathleen), Beattie, M.S. (Mary), Southey, M.C. (Melissa), Imyanitov, E.N. (Evgeny), Tischkowitz, M. (Marc), Janavicius, R. (Ramunas), John, E.M. (Esther), Kwong, A. (Ava), Diez, O. (Orland), Balmana, J. (Judith), Barkardottir, R.B. (Rosa), Arun, B.K. (Banu), Rennert, G. (Gad), Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Campbell, I. (Ian), Hout, A.H. (Annemarie) van der, Deurzen, C.H.M. (Carolien) van, Seynaeve, C.M. (Caroline), Gómez García, E.B. (Encarna), Leeuwen, F.E. (Flora) van, Meijers-Heijboer, H. (Hanne), Gille, J.J. (Johan), Ausems, M.G.E.M. (Margreet), Blok, M.J. (Marinus), Ligtenberg, M.J. (Marjolijn), Rookus, M.A. (Matti), Devilee, P. (Peter), Verhoef, S., Os, T.A.M. (Theo) van, Wijnen, J.T. (Juul), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Eccles, D. (Diana), Cook, J. (Jackie), Brewer, C. (C.), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Side, L. (Lucy), Donaldson, A. (Alan), Houghton, C. (Catherine), Rogers, M.T. (Mark), Dorkins, H. (Huw), Eason, J. (Jacqueline), Gregory, H. (Helen), McCann, E. (Emma), Murray, A. (Alexandra), Calender, A. (Alain), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Delnatte, C.D. (Capucine), Nogues, C. (Catherine), Lasset, C. (Christine), Houdayer, C. (Claude), Leroux, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Sobol, H. (Hagay), Coupier, I. (Isabelle), Vénat-Bouvet, L. (Laurence), Castera, L. (Laurent), Gauthier-Villars, M. (Marion), Léone, M. (Mélanie), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Bignon, Y.-J. (Yves-Jean), Złowocka-Perłowska, E. (Elzbieta), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Spurdle, A.B. (Amanda), Viel, A. (Alessandra), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Melloni, G. (Giulia), Ottini, L. (Laura), Papi, L. (Laura), Varesco, L. (Liliana), Tibiletti, M.G. (Maria Grazia), Peterlongo, P. (Paolo), Volorio, S. (Sara), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Arnold, N. (Norbert), Engel, C. (Christoph), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Gehrig, P.A. (Paola A.), Kast, K. (Karin), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Niederacher, D. (Dieter), Ditsch, N. (Nina), Plendl, H. (Hansjoerg), Preisler-Adams, S. (Sabine), Engert, S. (Stefanie), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Weber, B.H.F. (Bernhard), Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Loman, N. (Niklas), Rosenquist, R. (R.), Einbeigi, Z. (Zakaria), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Blank, S.V. (Stephanie), Cohn, D.E. (David), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Friedlander, M. (Michael), Bae-Jump, V.L. (Victoria L.), Fink-Retter, A. (Anneliese), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Lindor, N.M. (Noralane), Kaufman, B. (Bella), Shimon Paluch, S. (Shani), Laitman, Y. (Yael), Skytte, A.-B. (Anne-Bine), Gerdes, A-M. (Anne-Marie), Pedersen, I.S. (Inge Sokilde), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Vijai, J. (Joseph), Sarrel, K. (Kara), Robson, M. (Mark), Kauff, N. (Noah), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Ejlertsen, B. (Bent), Nielsen, F.C. (Finn), Jønson, L. (Lars), Andersen, M.K. (Mette), Ding, Y.C. (Yuan), Steele, L. (Linda), Foretova, L. (Lenka), Teulé, A. (A.), Lázaro, C. (Conxi), Brunet, J. (Joan), Pujana, M.A. (Miguel), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Narod, S. (Steven), Herzog, J. (Josef), Sand, S.R. (Sharon), Tognazzo, S. (Silvia), Agata, S. (Simona), Vaszko, T. (Tibor), Weaver, J. (JoEllen), Stavropoulou, A. (Alexandra), Buys, S.S. (Saundra), Romero, A. (Alfonso), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Durán, M. (Mercedes), Chung, W.K. (Wendy), Lasa, A. (Adriana), Dorfling, C.M. (Cecelia), Miron, A. (Alexander), Benítez, J. (Javier), Senter, L. (Leigha), Huo, D. (Dezheng), Chan, S. (Salina), Sokolenko, A. (Anna), Chiquette, J. (Jocelyne), Tihomirova, L. (Laima), Friebel, M.O.W. (Mark ), Agnarsson, B.A. (Bjarni), Lu, K.H. (Karen), Lejbkowicz, F. (Flavio), James, P.A. (Paul ), Hall, A.S. (Alistair), Dunning, A.M. (Alison), Tessier, Y. (Yann), Cunningham, J. (Jane), Slager, S. (Susan), Wang, C. (Chen), Hart, S. (Stewart), Stevens, K. (Kristen), Simard, J. (Jacques), Pastinen, T. (Tomi), Pankratz, V.S. (Shane), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Thorne, H. (Heather), Niedermayr, E. (Eveline), Borg, Å. (Åke), Olsson, H., Jernström, H. (H.), Henriksson, K. (Karin), Harbst, K. (Katja), Soller, M. (Maria), Kristoffersson, U. (Ulf), Wang, X. (Xianshu), Öfverholm, A. (Anna), Nordling, M. (Margareta), Karlsson, P. (Per), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Lindblom, A. (Annika), Bustinza, G.B., Rantala, J. (Johanna), Melin, B. (Beatrice), Ardnor, C.E. (Christina Edwinsdotter), Emanuelsson, M. (Monica), Ehrencrona, H. (Hans), Pigg, M.H. (Maritta ), Liedgren, S. (Sigrun), Rookus, M.A. (M.), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Aalfs, C.M. (Cora), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gomez Garcia, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Anna), Kennedy, M.J. (John), Barton, D.E. (David), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Brady, A.F. (Angela), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Lalloo, F. (Fiona), Taylor, J. (James), Male, A. (Alison), Berlin, C. (Cheryl), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Stormorken, A. (Astrid), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Buecher, B. (Bruno), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Handallou, S. (Sandrine), hardouin, A. (Agnès), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Lidereau, R. (Rosette), Demange, L. (Liliane), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Frenay, M. (Marc), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Sokolowska, J. (Johanna), Bronner, M. (Myriam), Lynch, H. (Henry), Snyder, C.L. (Carrie), Angelakos, M. (Maggie), Maskiell, J. (Judi), Dite, G.S. (Gillian), Couch, F.J. (Fergus), McGuffog, L. (Lesley), Lee, A. (Andrew), Olswold, C. (Curtis), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Fredericksen, Z. (Zachary), Barrowdale, D. (Daniel), Dennis, J. (Joe), Gaudet, M.M. (Mia), Dicks, E. (Ed), Kosel, M. (Matthew), Healey, S. (Sue), Sinilnikova, O. (Olga), Bacot, F. (Francois), Vincent, D. (Daniel), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Jakubowska, A. (Anna), Radice, P. (Paolo), Schmutzler, R.K. (Rita), Domchek, S.M. (Susan), Piedmonte, M. (Marion), Singer, C.F. (Christian), Friedman, E. (Eitan), Thomassen, M. (Mads), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Szabo, C. (Csilla), Blanco, I. (Ignacio), Greene, M.H. (Mark), Karlan, B.Y. (Beth), Garber, J., Phelan, C. (Catherine), Weitzel, J.N. (Jeffrey), Montagna, M. (Marco), Olah, E., Andrulis, I.L. (Irene), Godwin, A.K. (Andrew), Yannoukakos, D. (Drakoulis), Goldgar, D. (David), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Terry, M.-B. (Mary-Beth), Daly, M.B. (Mary), Rensburg, E.J. (Elizabeth) van, Hamann, U. (Ute), Ramus, S.J. (Susan), Ewart-Toland, A. (Amanda), Caligo, M.A. (Maria), Olopade, O.I. (Olofunmilayo), Tung, N. (Nadine), Claes, K. (Kathleen), Beattie, M.S. (Mary), Southey, M.C. (Melissa), Imyanitov, E.N. (Evgeny), Tischkowitz, M. (Marc), Janavicius, R. (Ramunas), John, E.M. (Esther), Kwong, A. (Ava), Diez, O. (Orland), Balmana, J. (Judith), Barkardottir, R.B. (Rosa), Arun, B.K. (Banu), Rennert, G. (Gad), Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Campbell, I. (Ian), Hout, A.H. (Annemarie) van der, Deurzen, C.H.M. (Carolien) van, Seynaeve, C.M. (Caroline), Gómez García, E.B. (Encarna), Leeuwen, F.E. (Flora) van, Meijers-Heijboer, H. (Hanne), Gille, J.J. (Johan), Ausems, M.G.E.M. (Margreet), Blok, M.J. (Marinus), Ligtenberg, M.J. (Marjolijn), Rookus, M.A. (Matti), Devilee, P. (Peter), Verhoef, S., Os, T.A.M. (Theo) van, Wijnen, J.T. (Juul), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Izatt, L. (Louise), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Eccles, D. (Diana), Cook, J. (Jackie), Brewer, C. (C.), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Side, L. (Lucy), Donaldson, A. (Alan), Houghton, C. (Catherine), Rogers, M.T. (Mark), Dorkins, H. (Huw), Eason, J. (Jacqueline), Gregory, H. (Helen), McCann, E. (Emma), Murray, A. (Alexandra), Calender, A. (Alain), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Delnatte, C.D. (Capucine), Nogues, C. (Catherine), Lasset, C. (Christine), Houdayer, C. (Claude), Leroux, D. (Dominique), Rouleau, E. (Etienne), Prieur, F. (Fabienne), Damiola, F. (Francesca), Sobol, H. (Hagay), Coupier, I. (Isabelle), Vénat-Bouvet, L. (Laurence), Castera, L. (Laurent), Gauthier-Villars, M. (Marion), Léone, M. (Mélanie), Pujol, P. (Pascal), Mazoyer, S. (Sylvie), Bignon, Y.-J. (Yves-Jean), Złowocka-Perłowska, E. (Elzbieta), Gronwald, J. (Jacek), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska, K. (Katarzyna), Huzarski, T. (Tomasz), Spurdle, A.B. (Amanda), Viel, A. (Alessandra), Peissel, B. (Bernard), Bonnani, B. (Bernardo), Melloni, G. (Giulia), Ottini, L. (Laura), Papi, L. (Laura), Varesco, L. (Liliana), Tibiletti, M.G. (Maria Grazia), Peterlongo, P. (Paolo), Volorio, S. (Sara), Manoukian, S. (Siranoush), Pensotti, V. (Valeria), Arnold, N. (Norbert), Engel, C. (Christoph), Deissler, H. (Helmut), Gadzicki, D. (Dorothea), Gehrig, P.A. (Paola A.), Kast, K. (Karin), Rhiem, K. (Kerstin), Meindl, A. (Alfons), Niederacher, D. (Dieter), Ditsch, N. (Nina), Plendl, H. (Hansjoerg), Preisler-Adams, S. (Sabine), Engert, S. (Stefanie), Sutter, C. (Christian), Varon-Mateeva, R. (Raymonda), Wapenschmidt, B. (Barbara), Weber, B.H.F. (Bernhard), Arver, B. (Brita Wasteson), Stenmark-Askmalm, M. (M.), Loman, N. (Niklas), Rosenquist, R. (R.), Einbeigi, Z. (Zakaria), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Blank, S.V. (Stephanie), Cohn, D.E. (David), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Friedlander, M. (Michael), Bae-Jump, V.L. (Victoria L.), Fink-Retter, A. (Anneliese), Rappaport, C. (Christine), Gschwantler-Kaulich, D. (Daphne), Pfeiler, G. (Georg), Tea, M.-K., Lindor, N.M. (Noralane), Kaufman, B. (Bella), Shimon Paluch, S. (Shani), Laitman, Y. (Yael), Skytte, A.-B. (Anne-Bine), Gerdes, A-M. (Anne-Marie), Pedersen, I.S. (Inge Sokilde), Moeller, S.T. (Sanne Traasdahl), Kruse, T.A. (Torben), Jensen, U.B., Vijai, J. (Joseph), Sarrel, K. (Kara), Robson, M. (Mark), Kauff, N. (Noah), Mulligan, A.M. (Anna Marie), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Ejlertsen, B. (Bent), Nielsen, F.C. (Finn), Jønson, L. (Lars), Andersen, M.K. (Mette), Ding, Y.C. (Yuan), Steele, L. (Linda), Foretova, L. (Lenka), Teulé, A. (A.), Lázaro, C. (Conxi), Brunet, J. (Joan), Pujana, M.A. (Miguel), Mai, P.L. (Phuong), Loud, J.T. (Jennifer), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Orsulic, S. (Sandra), Narod, S. (Steven), Herzog, J. (Josef), Sand, S.R. (Sharon), Tognazzo, S. (Silvia), Agata, S. (Simona), Vaszko, T. (Tibor), Weaver, J. (JoEllen), Stavropoulou, A. (Alexandra), Buys, S.S. (Saundra), Romero, A. (Alfonso), Hoya, M. (Miguel) de La, Aittomäki, K. (Kristiina), Muranen, T.A. (Taru), Durán, M. (Mercedes), Chung, W.K. (Wendy), Lasa, A. (Adriana), Dorfling, C.M. (Cecelia), Miron, A. (Alexander), Benítez, J. (Javier), Senter, L. (Leigha), Huo, D. (Dezheng), Chan, S. (Salina), Sokolenko, A. (Anna), Chiquette, J. (Jocelyne), Tihomirova, L. (Laima), Friebel, M.O.W. (Mark ), Agnarsson, B.A. (Bjarni), Lu, K.H. (Karen), Lejbkowicz, F. (Flavio), James, P.A. (Paul ), Hall, A.S. (Alistair), Dunning, A.M. (Alison), Tessier, Y. (Yann), Cunningham, J. (Jane), Slager, S. (Susan), Wang, C. (Chen), Hart, S. (Stewart), Stevens, K. (Kristen), Simard, J. (Jacques), Pastinen, T. (Tomi), Pankratz, V.S. (Shane), Offit, K. (Kenneth), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Thorne, H. (Heather), Niedermayr, E. (Eveline), Borg, Å. (Åke), Olsson, H., Jernström, H. (H.), Henriksson, K. (Karin), Harbst, K. (Katja), Soller, M. (Maria), Kristoffersson, U. (Ulf), Wang, X. (Xianshu), Öfverholm, A. (Anna), Nordling, M. (Margareta), Karlsson, P. (Per), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Lindblom, A. (Annika), Bustinza, G.B., Rantala, J. (Johanna), Melin, B. (Beatrice), Ardnor, C.E. (Christina Edwinsdotter), Emanuelsson, M. (Monica), Ehrencrona, H. (Hans), Pigg, M.H. (Maritta ), Liedgren, S. (Sigrun), Rookus, M.A. (M.), Verhoef, S. (S.), Schmidt, M.K. (Marjanka), Lange, J.L. (J.) de, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Hooning, M.J. (Maartje), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Cronenburg, T.C.T.E.F. van, Kets, C.M. (Marleen), Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Aalfs, C.M. (Cora), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gomez Garcia, E.B. (Encarna), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Anna), Kennedy, M.J. (John), Barton, D.E. (David), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Brady, A.F. (Angela), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Lalloo, F. (Fiona), Taylor, J. (James), Male, A. (Alison), Berlin, C. (Cheryl), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Stormorken, A. (Astrid), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Barjhoux, L. (Laure), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Buecher, B. (Bruno), Moncoutier, V. (Virginie), Belotti, M. (Muriel), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Uhrhammer, N. (Nancy), Bonadona, V. (Valérie), Handallou, S. (Sandrine), hardouin, A. (Agnès), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Lidereau, R. (Rosette), Demange, L. (Liliane), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Longy, M. (Michel), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Lebrun, M. (Marine), Kientz, C. (Caroline), Ferrer, S.F., Frenay, M. (Marc), Mortemousque, I. (Isabelle), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Sokolowska, J. (Johanna), Bronner, M. (Myriam), Lynch, H. (Henry), Snyder, C.L. (Carrie), Angelakos, M. (Maggie), Maskiell, J. (Judi), and Dite, G.S. (Gillian)
Abstract: BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associati
Published: 2013
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29. Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk

Author: Gaudet, M.M. (Mia), Kuchenbaecker, K.B. (Karoline), Vijai, J. (Joseph), Klein, R.J. (Robert), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Dunning, A.M. (Alison), Lee, A. (Andrew), Dennis, J. (Joe), Healey, S. (Sue), Dicks, E. (Ed), Soucy, P. (Penny), Sinilnikova, O. (Olga), Pankratz, V.S. (Shane), Wang, X. (Xing), Eldridge, S. (Steve), Tessier, Y. (Yann), Vincent, D. (Daniel), Bacot, F. (Francois), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Peterlongo, P. (Paolo), Schmutzler, R.K. (Rita), Nathanson, K.L. (Katherine), Piedmonte, M. (Marion), Singer, C.F. (Christian), Thomassen, M. (Mads), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Blanco, I. (Ignacio), Greene, M.H. (Mark), Garber, J., Weitzel, J.N. (Jeffrey), Andrulis, I.L. (Irene), Goldgar, D. (David), D'Andrea, E. (Emma), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Rensburg, E.J. (Elizabeth) van, Arason, A. (Adalgeir), Rennert, G. (Gad), Ouweland, A.M.W. (Ans) van den, Hout, A.H. (Annemarie) van der, Kets, C.M. (Marleen), Aalfs, C.M. (Cora), Wijnen, J.T. (Juul), Ausems, M.G.E.M. (Margreet), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Jacobs, C. (Chris), Adlard, J.W. (Julian), Tischkowitz, M. (Marc), Porteous, M.E. (Mary), Damiola, F. (Francesca), Golmard, L. (Lisa), Barjhoux, L. (Laure), Longy, M. (Michel), Belotti, M. (Muriel), Ferrer, S.F., Mazoyer, S. (Sylvie), Spurdle, A.B. (Amanda), Manoukian, S. (Siranoush), Barile, M. (Monica), Genuardi, M. (Maurizio), Arnold, N. (Norbert), Meindl, A. (Alfons), Sutter, C. (Christian), Wapenschmidt, B. (Barbara), Domchek, S.M. (Susan), Pfeiler, G. (Georg), Friedman, E. (Eitan), Jensen, U.B., Robson, M. (Mark), Shah, S. (Sonia), Lázaro, C. (Conxi), Mai, P.L. (Phuong), Benítez, J. (Javier), Southey, M.C. (Melissa), Schmidt, M.K. (Marjanka), Fasching, P.A. (Peter), Peto, J. (Julian), Humphreys, M.K. (Manjeet), Wang, Q. (Qing), Michailidou, K. (Kyriaki), Sawyer, E.J. (Elinor), Burwinkel, B. (Barbara), Guénel, P. (Pascal), Bojesen, S.E. (Stig), Milne, R.L. (Roger), Brenner, H. (Hermann), Lochmann, M. (Magdalena), Brauch, H. (Hiltrud), Ko, Y-D. (Yon-Dschun), Baisch, C. (Christian), Fischer, H.-P., Bruening, T. (Thomas), Pesch, B. (Beate), Rabstein, S. (Sylvia), Spickenheuer, A. (Anne), Aittomäki, K. (Kristiina), Dörk, T. (Thilo), Margolin, S. (Sara), Mannermaa, A. (Arto), Lambrechts, D. (Diether), Chang-Claude, J. (Jenny), Radice, P. (Paolo), Giles, G.G. (Graham), Haiman, C.A. (Christopher), Winqvist, R. (Robert), Devillee, P. (Peter), García-Closas, M. (Montserrat), Schoof, N. (Nils), Hooning, M.J. (Maartje), Cox, A. (Angela), Pharoah, P.D.P. (Paul), Jakubowska, A. (Anna), Orr, N. (Nick), González-Neira, A. (Anna), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Hall, A.S. (Alistair), Couch, F.J. (Fergus), Simard, J. (Jacques), Altshuler, D. (David), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Offit, K. (Kenneth), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Verhoef, S., Lange, J.L. (J.) de, Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Devilee, P. (Peter), Cronenburg, T.C.T.E.F. van, Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Gille, J.J. (Johan), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Blok, M.J. (Marinus), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Donaldson, A. (Alan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Kennedy, M.J. (John), Barton, D.E. (David), Drummond, S. (Sarah), Brewer, C. (C.), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Izatt, L. (Louise), Langman, C. (Caroline), Brady, A.F. (Angela), Dorkins, H. (Huw), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Houghton, C. (Catherine), Lalloo, F. (Fiona), Taylor, J. (James), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Douglas, F. (Fiona), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Eeles, R. (Rosalind), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Cook, J. (Jackie), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Hodgson, S.V. (Shirley), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Eccles, D. (Diana), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Léone, M. (Mélanie), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Houdayer, C. (Claude), Moncoutier, V. (Virginie), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Handallou, S. (Sandrine), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Coupier, I. (Isabelle), Pujol, P. (Pascal), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Rouleau, E. (Etienne), Lidereau, R. (Rosette), Demange, L. (Liliane), Nogues, C. (Catherine), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Frenay, M. (Marc), Vénat-Bouvet, L. (Laurence), Delnatte, C.D. (Capucine), Mortemousque, I. (Isabelle), Lynch, H. (Henry), Snyder, C.L. (Carrie), Gaudet, M.M. (Mia), Kuchenbaecker, K.B. (Karoline), Vijai, J. (Joseph), Klein, R.J. (Robert), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Dunning, A.M. (Alison), Lee, A. (Andrew), Dennis, J. (Joe), Healey, S. (Sue), Dicks, E. (Ed), Soucy, P. (Penny), Sinilnikova, O. (Olga), Pankratz, V.S. (Shane), Wang, X. (Xing), Eldridge, S. (Steve), Tessier, Y. (Yann), Vincent, D. (Daniel), Bacot, F. (Francois), Hogervorst, F.B.L. (Frans), Peock, S. (Susan), Stoppa-Lyonnet, D. (Dominique), Coulet, F. (Florence), Colas, C. (Chrystelle), Soubrier, F., Peterlongo, P. (Paolo), Schmutzler, R.K. (Rita), Nathanson, K.L. (Katherine), Piedmonte, M. (Marion), Singer, C.F. (Christian), Thomassen, M. (Mads), Sokolowska, J. (Johanna), Bronner, M. (Myriam), Hansen, T.V.O. (Thomas), Neuhausen, S.L. (Susan), Blanco, I. (Ignacio), Greene, M.H. (Mark), Garber, J., Weitzel, J.N. (Jeffrey), Andrulis, I.L. (Irene), Goldgar, D. (David), D'Andrea, E. (Emma), Caldes, T. (Trinidad), Nevanlinna, H. (Heli), Osorio, A. (Ana), Rensburg, E.J. (Elizabeth) van, Arason, A. (Adalgeir), Rennert, G. (Gad), Ouweland, A.M.W. (Ans) van den, Hout, A.H. (Annemarie) van der, Kets, C.M. (Marleen), Aalfs, C.M. (Cora), Wijnen, J.T. (Juul), Ausems, M.G.E.M. (Margreet), Frost, D. (Debra), Ellis, S. (Steve), Fineberg, E. (Elena), Platte, R. (Radka), Evans, D.G. (Gareth), Jacobs, C. (Chris), Adlard, J.W. (Julian), Tischkowitz, M. (Marc), Porteous, M.E. (Mary), Damiola, F. (Francesca), Golmard, L. (Lisa), Barjhoux, L. (Laure), Longy, M. (Michel), Belotti, M. (Muriel), Ferrer, S.F., Mazoyer, S. (Sylvie), Spurdle, A.B. (Amanda), Manoukian, S. (Siranoush), Barile, M. (Monica), Genuardi, M. (Maurizio), Arnold, N. (Norbert), Meindl, A. (Alfons), Sutter, C. (Christian), Wapenschmidt, B. (Barbara), Domchek, S.M. (Susan), Pfeiler, G. (Georg), Friedman, E. (Eitan), Jensen, U.B., Robson, M. (Mark), Shah, S. (Sonia), Lázaro, C. (Conxi), Mai, P.L. (Phuong), Benítez, J. (Javier), Southey, M.C. (Melissa), Schmidt, M.K. (Marjanka), Fasching, P.A. (Peter), Peto, J. (Julian), Humphreys, M.K. (Manjeet), Wang, Q. (Qing), Michailidou, K. (Kyriaki), Sawyer, E.J. (Elinor), Burwinkel, B. (Barbara), Guénel, P. (Pascal), Bojesen, S.E. (Stig), Milne, R.L. (Roger), Brenner, H. (Hermann), Lochmann, M. (Magdalena), Brauch, H. (Hiltrud), Ko, Y-D. (Yon-Dschun), Baisch, C. (Christian), Fischer, H.-P., Bruening, T. (Thomas), Pesch, B. (Beate), Rabstein, S. (Sylvia), Spickenheuer, A. (Anne), Aittomäki, K. (Kristiina), Dörk, T. (Thilo), Margolin, S. (Sara), Mannermaa, A. (Arto), Lambrechts, D. (Diether), Chang-Claude, J. (Jenny), Radice, P. (Paolo), Giles, G.G. (Graham), Haiman, C.A. (Christopher), Winqvist, R. (Robert), Devillee, P. (Peter), García-Closas, M. (Montserrat), Schoof, N. (Nils), Hooning, M.J. (Maartje), Cox, A. (Angela), Pharoah, P.D.P. (Paul), Jakubowska, A. (Anna), Orr, N. (Nick), González-Neira, A. (Anna), Pita, G. (Guillermo), Alonso, M.R. (Rosario), Hall, A.S. (Alistair), Couch, F.J. (Fergus), Simard, J. (Jacques), Altshuler, D. (David), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Antoniou, A.C. (Antonis), Offit, K. (Kenneth), Rookus, M.A. (Matti), Leeuwen, F.E. (Flora) van, Verhoef, S., Lange, J.L. (J.) de, Collée, J.M. (Margriet), Seynaeve, C.M. (Caroline), Deurzen, C.H.M. (Carolien) van, Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Devilee, P. (Peter), Cronenburg, T.C.T.E.F. van, Mensenkamp, A.R. (Arjen), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Gille, J.J. (Johan), Waisfisz, Q. (Quinten), Meijers-Heijboer, E.J. (Hanne), Gómez García, E.B. (Encarna), Blok, M.J. (Marinus), Oosterwijk, J.C. (Jan), Mourits, M.J. (Marjan), Bock, G.H. (Geertruida) de, Vasen, H. (Hans), Ellis, S.D. (Steve), Miedzybrodzka, Z. (Zosia), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), Ong, K.-R. (Kai-Ren), Hoffman, J. (Jonathan), Donaldson, A. (Alan), James, M. (Margaret), Paterson, J. (Joan), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Kennedy, M.J. (John), Barton, D.E. (David), Drummond, S. (Sarah), Brewer, C. (C.), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Davidson, R. (Rosemarie), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Izatt, L. (Louise), Langman, C. (Caroline), Brady, A.F. (Angela), Dorkins, H. (Huw), Melville, S.A. (Scott), Randhawa, K. (Kashmir), Barwell, J. (Julian), Serra-Feliu, G. (Gemma), Ellis, I.O. (Ian), Houghton, C. (Catherine), Lalloo, F. (Fiona), Taylor, J. (James), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Douglas, F. (Fiona), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Eeles, R. (Rosalind), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Killick, S.R., Martin, S. (Sue), Rea, D. (Dan), Kulkarni, A. (Anjana), Cook, J. (Jackie), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Hodgson, S.V. (Shirley), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lehmann, A. (Anna), Eccles, D. (Diana), Lucassen, A. (Anneke), Crawford, G. (Gabe), McBride, D. (Donna), Smalley, S. (Sarah), Verny-Pierre, C. (Carole), Giraud, S. (Sophie), Léone, M. (Mélanie), Gauthier-Villars, M. (Marion), Buecher, B. (Bruno), Houdayer, C. (Claude), Moncoutier, V. (Virginie), Tirapo, C. (Carole), Pauw, A. (Antoine) de, Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Lasset, C. (Christine), Bonadona, V. (Valérie), Handallou, S. (Sandrine), Hardouin, A. (Agnès), Berthet, P. (Pascaline), Sobol, H. (Hagay), Bourdon, V. (Violaine), Noguchi, T. (Tetsuro), Remenieras, A. (Audrey), Eisinger, F. (François), Coupier, I. (Isabelle), Pujol, P. (Pascal), Peyrat, J.-P., Fournier, J. (Joëlle), Révillion, F. (Françoise), Vennin, P. (Philippe), Adenis, C. (Claude), Rouleau, E. (Etienne), Lidereau, R. (Rosette), Demange, L. (Liliane), Nogues, C. (Catherine), Muller, D.W. (Danièle), Fricker, J.P. (Jean Pierre), Barouk-Simonet, E. (Emmanuelle), Bonnet, F. (Françoise), Bubien, V. (Virginie), Sevenet, N. (Nicolas), Toulas, C. (Christine), Guimbaud, R. (Rosine), Gladieff, L. (Laurence), Feillel, V. (Viviane), Dreyfus, H. (Hélène), Rebischung, C. (Christine), Peysselon, M. (Magalie), Coron, F. (Fanny), Faivre, L. (Laurence), Prieur, F. (Fabienne), Lebrun, M. (Marine), Kientz, C. (Caroline), Frenay, M. (Marc), Vénat-Bouvet, L. (Laurence), Delnatte, C.D. (Capucine), Mortemousque, I. (Isabelle), Lynch, H. (Henry), and Snyder, C.L. (Carrie)
Published: 2013
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30. Common variants at the 19p13.1 and ZNF365 loci are associated with ER subtypes of breast cancer and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

Author: Couch, F.J. (Fergus), Gaudet, M.M. (Mia), Antoniou, A.C. (Antonis), Ramus, S.J. (Susan), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Wang, X. (Xing), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Lee, A. (Andrew), Healey, S. (Sue), Sinilnikova, O. (Olga), Andrulis, I.L. (Irene), Ozcelik, H. (Hilmi), Mulligan, A.M. (Anna Marie), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Jensen, U.B., Skytte, A.-B. (Anne-Bine), Kruse, T.A. (Torben), Caligo, M.A. (Maria), Wachenfeldt, A. (Anna) von, Barbany-Bustinza, G. (Gisela), Loman, N. (Niklas), Soller, M. (Maria), Ehrencrona, H. (Hans), Karlsson, P. (Per), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Zołwocka, E. (Elzbieta), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.I., Benítez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Os, T.A.M. (Theo) van, Leeuwen, F. (Fred) van, Meijers-Heijboer, E.J. (Hanne), Wijnen, J.T. (Juul), Blok, M.J. (Marinus), Kets, C.M. (Marleen), Hooning, M.J. (Maartje), Oldenburg, R.A. (Rogier), Ausems, M.G.E.M. (Margreet), Peock, S. (Susan), Frost, D. (Debra), Ellis, S.D. (Steve), Platte, R. (Radka), Fineberg, E. (Elena), Evans, D.G. (Gareth), Jacobs, C. (Chris), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T.J. (Trevor), Cook, J. (Jackie), Paterson, J. (Joan), Brewer, C. (Carole), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Side, L. (Lucy), Bove, B. (B.), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Fassy-Colcombet, M. (Marion), Castera, L. (Laurent), Cornelis, F. (Franco̧is), Mazoyer, S. (Sylvie), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Pujol, P. (Pascal), Coupier, I. (Isabelle), Delnatte, C.D. (Capucine), Akloul, L. (Linda), Lynch, H. (Henry), Snyder, C.L. (Carrie), Buys, S.S. (Saundra), Daly, M.B. (Mary), Terry, M.-B. (Mary-Beth), Chung, W. (Wendy), John, E.M. (Esther), Miron, A. (Alexander), Southey, M.C. (Melissa), Hopper, J.L. (John), Goldgar, D. (David), Singer, C.F. (Christian), Rappaport, C. (Christine), Tea, M.-K., Fink-Retter, A. (Anneliese), Hansen, T.V.O. (Thomas), Nielsen, F.C. (Finn), Arason, A. (Adalgeir), Vijai, J. (Joseph), Shah, S. (Sonia), Sarrel, K. (Kara), Robson, M. (Mark), Piedmonte, M. (Marion), Phillips, K. (Kelly), Basil, J. (Jack), Rubinstein, W.S. (Wendy), Boggess, J.F. (John), Wakeley, K. (Katie), Ewart-Toland, A. (Amanda), Montagna, M. (Marco), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Feliubadaló, L. (L.), Brunet, J. (Joan), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Odunsi, K. (Kunle), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E., Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Dorfling, C.M. (Cecelia), Diez, O. (Orland), Kwong, A. (Ava), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Heidemann, S. (Simone), Niederacher, D. (Dieter), Preisler-Adams, S. (Sabine), Gadzicki, D. (Dorothea), Varon-Mateeva, R. (Raymonda), Deissler, H. (Helmut), Gehrig, P.A. (Paola A.), Sutter, C. (Christian), Kast, K. (Karin), Fiebig, B. (Britta), Heinritz, W. (Wolfram), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Muranen, T.A. (Taru), Nevanlinna, H. (Heli), Tischkowitz, M. (Marc), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Lindor, N.M. (Noralane), Fredericksen, Z. (Zachary), Pankratz, V.S. (Shane), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Barile, M. (Monica), Bernard, L. (Loris), Viel, A. (Alessandra), Giannini, G. (Giuseppe), Varesco, L. (Liliana), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), Simard, J. (Jacques), Couch, F.J. (Fergus), Gaudet, M.M. (Mia), Antoniou, A.C. (Antonis), Ramus, S.J. (Susan), Kuchenbaecker, K.B. (Karoline), Soucy, P. (Penny), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Wang, X. (Xing), Kircchoff, T. (Tomas), McGuffog, L. (Lesley), Barrowdale, D. (Daniel), Lee, A. (Andrew), Healey, S. (Sue), Sinilnikova, O. (Olga), Andrulis, I.L. (Irene), Ozcelik, H. (Hilmi), Mulligan, A.M. (Anna Marie), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Jensen, U.B., Skytte, A.-B. (Anne-Bine), Kruse, T.A. (Torben), Caligo, M.A. (Maria), Wachenfeldt, A. (Anna) von, Barbany-Bustinza, G. (Gisela), Loman, N. (Niklas), Soller, M. (Maria), Ehrencrona, H. (Hans), Karlsson, P. (Per), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Jaworska, K. (Katarzyna), Durda, K. (Katarzyna), Zołwocka, E. (Elzbieta), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.I., Benítez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Os, T.A.M. (Theo) van, Leeuwen, F. (Fred) van, Meijers-Heijboer, E.J. (Hanne), Wijnen, J.T. (Juul), Blok, M.J. (Marinus), Kets, C.M. (Marleen), Hooning, M.J. (Maartje), Oldenburg, R.A. (Rogier), Ausems, M.G.E.M. (Margreet), Peock, S. (Susan), Frost, D. (Debra), Ellis, S.D. (Steve), Platte, R. (Radka), Fineberg, E. (Elena), Evans, D.G. (Gareth), Jacobs, C. (Chris), Eeles, R. (Rosalind), Adlard, J.W. (Julian), Davidson, R. (Rosemarie), Eccles, D. (Diana), Cole, T.J. (Trevor), Cook, J. (Jackie), Paterson, J. (Joan), Brewer, C. (Carole), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Morrison, P.J. (Patrick), Walker, L.J. (Lisa), Porteous, M.E. (Mary), Kennedy, M.J. (John), Side, L. (Lucy), Bove, B. (B.), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Fassy-Colcombet, M. (Marion), Castera, L. (Laurent), Cornelis, F. (Franco̧is), Mazoyer, S. (Sylvie), Léone, M. (Mélanie), Boutry-Kryza, N. (N.), Bressac-de Paillerets, B. (Brigitte), Caron, O. (Olivier), Pujol, P. (Pascal), Coupier, I. (Isabelle), Delnatte, C.D. (Capucine), Akloul, L. (Linda), Lynch, H. (Henry), Snyder, C.L. (Carrie), Buys, S.S. (Saundra), Daly, M.B. (Mary), Terry, M.-B. (Mary-Beth), Chung, W. (Wendy), John, E.M. (Esther), Miron, A. (Alexander), Southey, M.C. (Melissa), Hopper, J.L. (John), Goldgar, D. (David), Singer, C.F. (Christian), Rappaport, C. (Christine), Tea, M.-K., Fink-Retter, A. (Anneliese), Hansen, T.V.O. (Thomas), Nielsen, F.C. (Finn), Arason, A. (Adalgeir), Vijai, J. (Joseph), Shah, S. (Sonia), Sarrel, K. (Kara), Robson, M. (Mark), Piedmonte, M. (Marion), Phillips, K. (Kelly), Basil, J. (Jack), Rubinstein, W.S. (Wendy), Boggess, J.F. (John), Wakeley, K. (Katie), Ewart-Toland, A. (Amanda), Montagna, M. (Marco), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Feliubadaló, L. (L.), Brunet, J. (Joan), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Odunsi, K. (Kunle), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E., Teo, S.-H. (Soo-Hwang), Ganz, P.A. (Patricia), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Dorfling, C.M. (Cecelia), Diez, O. (Orland), Kwong, A. (Ava), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Heidemann, S. (Simone), Niederacher, D. (Dieter), Preisler-Adams, S. (Sabine), Gadzicki, D. (Dorothea), Varon-Mateeva, R. (Raymonda), Deissler, H. (Helmut), Gehrig, P.A. (Paola A.), Sutter, C. (Christian), Kast, K. (Karin), Fiebig, B. (Britta), Heinritz, W. (Wolfram), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Muranen, T.A. (Taru), Nevanlinna, H. (Heli), Tischkowitz, M. (Marc), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Lindor, N.M. (Noralane), Fredericksen, Z. (Zachary), Pankratz, V.S. (Shane), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Barile, M. (Monica), Bernard, L. (Loris), Viel, A. (Alessandra), Giannini, G. (Giuseppe), Varesco, L. (Liliana), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Easton, D.F. (Douglas), Chenevix-Trench, G. (Georgia), Offit, K. (Kenneth), and Simard, J. (Jacques)
Abstract: Background: Genome-wide association studies (GWAS) identified variants at 19p13.1 and ZNF365 (10q21.2) as risk factors for breast cancer among BRCA1 and BRCA2 mutation carriers, respectively. We explored associations with ovarian cancer and with breast cancer by tumor histopathology for these variants in mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Methods: Genotyping data for 12,599 BRCA1 and 7,132 BRCA2 mutation carriers from 40 studies were combined. Results: We confirmed associations between rs8170 at 19p13.1 and breast cancer risk for BRCA1 mutation carriers [HR, 1.17; 95% confidence interval (CI), 1.07-1.27; P = 7.42 × 10 -4] and between rs16917302 at ZNF365 (HR, 0.84; 95% CI, 0.73-0.97; P = 0.017) but not rs311499 at 20q13.3 (HR, 1.11; 95% CI, 0.94-1.31; P = 0.22) and breast cancer risk for BRCA2 mutation carriers. Analyses based on tumor histopathology showed that 19p13 variants were predominantly associated with estrogen receptor (ER)-negative breast cancer for both BRCA1 and BRCA2 mutation carriers, whereas rs16917302 at ZNF365 was mainly associated with ER-positive breast cancer for both BRCA1 and BRCA2 mutation carriers.Wealso found for the first time that rs67397200 at 19p13.1 was associated with an increased risk of ovarian cancer for BRCA1 (HR, 1.16; 95% CI, 1.05-1.29; P = 3.8 × 10 -4) and BRCA2 mutation carriers (HR, 1.30; 95% CI, 1.10-1.52; P = 1.8 × 10-3). Conclusions: 19p13.1 and ZNF365 are susceptibility loci for ovarian cancer and ER subtypes of breast cancer among BRCA1 and BRCA2 mutation carriers. Impact: These findings can lead to an improved understanding of tumor development and may prove useful for breast and ovarian cancer risk prediction for BRCA1 and BRCA2 mutation carriers.
Published: 2012
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31. Breast density as indicator for the use of mammography or MRI to screen women with familial risk for breast cancer (FaMRIsc): A multicentre randomized controlled trial

Author: Saadatmand, S. (Sepideh), Rutgers, E.J.T. (Emiel), Tollenaar, R.A.E.M. (Rob), Zonderland, H.M. (Harmine), Ausems, M.G.E.M. (Margreet), Keymeulen, B. (Bart), Schlooz-Vries, M.S. (Margreet), Koppert, L.B. (Linetta), Heijnsdijk, E.A.M. (Eveline), Seynaeve, C.M. (Caroline), Verhoef, C. (Kees), Oosterwijk, J.C. (Jan), Obdeijn, A.I.M. (Inge-Marie), Koning, H.J. (Harry) de, Tilanus-Linthorst, M.M.A. (Madeleine), Saadatmand, S. (Sepideh), Rutgers, E.J.T. (Emiel), Tollenaar, R.A.E.M. (Rob), Zonderland, H.M. (Harmine), Ausems, M.G.E.M. (Margreet), Keymeulen, B. (Bart), Schlooz-Vries, M.S. (Margreet), Koppert, L.B. (Linetta), Heijnsdijk, E.A.M. (Eveline), Seynaeve, C.M. (Caroline), Verhoef, C. (Kees), Oosterwijk, J.C. (Jan), Obdeijn, A.I.M. (Inge-Marie), Koning, H.J. (Harry) de, and Tilanus-Linthorst, M.M.A. (Madeleine)
Abstract: Background: To reduce mortality, women with a family history of breast cancer often start mammography screening at a younger age than the general population. Breast density is high in over 50% of women younger than 50 years. With high breast density, breast cancer incidence increases, but sensitivity of mammography decreases. Therefore, mammography might not be the optimal method for breast cancer screening in young women. Adding MRI increases sensitivity, but also the risk of false-positive results. The limitation of all previous MRI screening studies is that they do not contain a comparison group; all participants received both MRI and mammography. Therefore, we cannot empirically assess in which stage tumours would have been detected by either test.The aim of the Familial MRI Screening Study (FaMRIsc) is to compare the efficacy of MRI screening to mammography for women with a familial risk. Furthermore, we will assess the influence of breast density.Methods/Design: This Dutch multicentre, randomized controlled trial, with balanced randomisation (1:1) has a parallel grouped design. Women with a cumulative lifetime risk for breast cancer due to their family history of ≥20%, aged 30-55 years are eligible. Identified BRCA1/2 mutation carriers or women with 50% risk of carrying a mutation are excluded. Group 1 receives yearly mammography and clinical breast examination (n = 1000), and group 2 yearly MRI and clinical breast examination, and mammography biennially (n = 1000).Primary endpoints are the number and stage of the detected breast cancers in each arm. Secondary endpoints are the number of false-positive results in both screening arms. Furthermore, sensitivity and positive predictive value of both screening strategies will be assessed. Cost-effectiveness of both strategies will be assessed. Analyses will also be performed with mammographic density as stratification factor.Discussion: Personalized breast cancer screening might optimize mortality reduction with le
Published: 2012
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32. Breast cancer risk and 6q22.33: Combined results from breast cancer association consortium and consortium of investigators on modifiers of brca1/2

Author: Kircchoff, T. (Tomas), Offit, K. (Kenneth), Gaudet, M.M. (Mia), Pharoah, P.D.P. (Paul), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), McGuffog, L. (Lesley), Humphreys, M.K. (Manjeet), Dunning, A.M. (Alison), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Flyger, H. (Henrik), Kang, D. (Daehee), Yoo, K-Y. (Keun-Young), Noh, D-Y. (Dong-Young), Ahn, S.-H. (Sei-Hyun), Dörk, T. (Thilo), Schürmann, P. (Peter), Karstens, J.H. (Johann), Hillemanns, P. (Peter), Couch, F.J. (Fergus), Olson, J.E. (Janet), Vachon, C. (Celine), Cox, A. (Angela), Brock, I.W. (Ian), Elliott, G. (Graeme), Reed, M.W.R. (Malcolm), Burwinkel, B. (Barbara), Meindl, A. (Alfons), Brauch, H. (Hiltrud), Justenhoven, C. (Christina), Hamann, U. (Ute), Ko, Y-D. (Yon-Dschun), Fischer, H.-P., Brüning, T. (Thomas), Pesch, B. (Beate), Harth, V. (Volker), Rabstein, S. (Sylvia), Broeks, A. (Annegien), Schmidt, M.K. (Marjanka), Veer, L.J. (Laura) van 't, Braaf, L.M. (Linde), Johnson, N. (Nichola), Fletcher, O. (Olivia), Gibson, L.J. (Lorna), Peto, J. (Julian), Turnbull, C. (Clare), Seal, S. (Sheila), Renwick, A. (Anthony), Rahman, N. (Nazneen), Wu, P.-E. (Pei-Ei), Yu, J-C. (Jyh-Cherng), Hsiung, C.-N. (Chia-Ni), Shen, C-Y. (Chen-Yang), Southey, M.C. (Melissa), Hopper, J.L. (John), Hammet, F. (Fleur), Dorpe, T. (Thijs) van, Dieudonné, A.-S. (Anne-Sophie), Hatse, S. (Sigrid), Lambrechts, D. (Diether), Andrulis, I.L. (Irene), Bogdanova, N.V. (Natalia), Antonenkova, N.N. (Natalia), Rogov, J.I. (Juri), Prokofieva, D. (Daria), Bermisheva, M. (Marina), Khusnutdinova, E.K. (Elza), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Hooning, M.J. (Maartje), Devilee, P. (Peter), Margolin, S. (Sara), Lindblom, A. (Annika), Milne, R.L. (Roger), Arias Pérez, J.I. (José Ignacio), Zamora, M.P. (Pilar), Benítez, J. (Javier), Severi, G. (Gianluca), Baglietto, L. (Laura), Giles, G.G. (Graham), Chenevix-Trench, G. (Georgia), Spurdle, A.B. (Amanda), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Holland, H. (Helene), Healey, S. (Sue), Wang-Gohrke, S. (Shan), Chang-Claude, J. (Jenny), Mannermaa, A. (Arto), Kosma, V-M. (Veli-Matti), Kauppinen, J. (Jaana), Kataja, V. (Vesa), Agnarsson, B.A. (Bjarni), Caligo, M.A. (Maria), Godwin, A.K. (Andrew), Nevanlinna, H. (Heli), Heikinen, T. (Tuomas), Fredericksen, Z. (Zachary), Lindor, N.M. (Noralane), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Loman, N. (Niklas), Karlsson, P. (Per), Askmalm, M.S. (Marie), Melin, B. (Beatrice), Wachenfeldt, A. (Anna) von, Hogervorst, F.B.L. (Frans), Verheus, M. (Martijn), Rookus, M.A. (Matti), Seynaeve, C.M. (Caroline), Oldenburg, R.A. (Rogier), Ligtenberg, M.J. (Marjolijn), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Gille, H.J.P. (Hans), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Luccarini, C. (Craig), Pichert, G. (Gabriella), Davidson, R. (Rosemarie), Eccles, D. (Diana), Ong, K.-R. (Kai-Ren), Cook, J. (Jackie), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Gold, B. (Bert), Wang, X. (Xianshu), Chu, C. (Carol), Kircchoff, T. (Tomas), Offit, K. (Kenneth), Gaudet, M.M. (Mia), Pharoah, P.D.P. (Paul), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), McGuffog, L. (Lesley), Humphreys, M.K. (Manjeet), Dunning, A.M. (Alison), Bojesen, S.E. (Stig), Nordestgaard, B.G. (Børge), Flyger, H. (Henrik), Kang, D. (Daehee), Yoo, K-Y. (Keun-Young), Noh, D-Y. (Dong-Young), Ahn, S.-H. (Sei-Hyun), Dörk, T. (Thilo), Schürmann, P. (Peter), Karstens, J.H. (Johann), Hillemanns, P. (Peter), Couch, F.J. (Fergus), Olson, J.E. (Janet), Vachon, C. (Celine), Cox, A. (Angela), Brock, I.W. (Ian), Elliott, G. (Graeme), Reed, M.W.R. (Malcolm), Burwinkel, B. (Barbara), Meindl, A. (Alfons), Brauch, H. (Hiltrud), Justenhoven, C. (Christina), Hamann, U. (Ute), Ko, Y-D. (Yon-Dschun), Fischer, H.-P., Brüning, T. (Thomas), Pesch, B. (Beate), Harth, V. (Volker), Rabstein, S. (Sylvia), Broeks, A. (Annegien), Schmidt, M.K. (Marjanka), Veer, L.J. (Laura) van 't, Braaf, L.M. (Linde), Johnson, N. (Nichola), Fletcher, O. (Olivia), Gibson, L.J. (Lorna), Peto, J. (Julian), Turnbull, C. (Clare), Seal, S. (Sheila), Renwick, A. (Anthony), Rahman, N. (Nazneen), Wu, P.-E. (Pei-Ei), Yu, J-C. (Jyh-Cherng), Hsiung, C.-N. (Chia-Ni), Shen, C-Y. (Chen-Yang), Southey, M.C. (Melissa), Hopper, J.L. (John), Hammet, F. (Fleur), Dorpe, T. (Thijs) van, Dieudonné, A.-S. (Anne-Sophie), Hatse, S. (Sigrid), Lambrechts, D. (Diether), Andrulis, I.L. (Irene), Bogdanova, N.V. (Natalia), Antonenkova, N.N. (Natalia), Rogov, J.I. (Juri), Prokofieva, D. (Daria), Bermisheva, M. (Marina), Khusnutdinova, E.K. (Elza), Asperen, C.J. (Christi) van, Tollenaar, R.A.E.M. (Rob), Hooning, M.J. (Maartje), Devilee, P. (Peter), Margolin, S. (Sara), Lindblom, A. (Annika), Milne, R.L. (Roger), Arias Pérez, J.I. (José Ignacio), Zamora, M.P. (Pilar), Benítez, J. (Javier), Severi, G. (Gianluca), Baglietto, L. (Laura), Giles, G.G. (Graham), Chenevix-Trench, G. (Georgia), Spurdle, A.B. (Amanda), Beesley, J. (Jonathan), Chen, X. (Xiaoqing), Holland, H. (Helene), Healey, S. (Sue), Wang-Gohrke, S. (Shan), Chang-Claude, J. (Jenny), Mannermaa, A. (Arto), Kosma, V-M. (Veli-Matti), Kauppinen, J. (Jaana), Kataja, V. (Vesa), Agnarsson, B.A. (Bjarni), Caligo, M.A. (Maria), Godwin, A.K. (Andrew), Nevanlinna, H. (Heli), Heikinen, T. (Tuomas), Fredericksen, Z. (Zachary), Lindor, N.M. (Noralane), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Loman, N. (Niklas), Karlsson, P. (Per), Askmalm, M.S. (Marie), Melin, B. (Beatrice), Wachenfeldt, A. (Anna) von, Hogervorst, F.B.L. (Frans), Verheus, M. (Martijn), Rookus, M.A. (Matti), Seynaeve, C.M. (Caroline), Oldenburg, R.A. (Rogier), Ligtenberg, M.J. (Marjolijn), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Gille, H.J.P. (Hans), Wijnen, J.T. (Juul), Gómez García, E.B. (Encarna), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Luccarini, C. (Craig), Pichert, G. (Gabriella), Davidson, R. (Rosemarie), Eccles, D. (Diana), Ong, K.-R. (Kai-Ren), Cook, J. (Jackie), Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Gold, B. (Bert), Wang, X. (Xianshu), and Chu, C. (Carol)
Abstract: Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I2 = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
Published: 2012
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33. Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Antoniou, A.C. (Antonis), Kartsonaki, C. (Christiana), Sinilnikova, O. (Olga), Soucy, P. (Penny), McGuffog, L. (Lesley), Healey, S. (Sue), Lee, A. (Andrew), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Cattaneo, E. (Elisa), Barile, M. (Monica), Pensotti, V. (Valeria), Pasini, B. (Barbara), Dolcetti, R. (Riccardo), Giannini, G. (Giuseppe), Putignano, A.L., Varesco, L. (Liliana), Radice, P. (Paolo), Mai, P.L. (Phuong), Greene, M.H. (Mark), Andrulis, I.L. (Irene), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Kruse, T.A. (Torben), Jensen, U.B., Cruger, D. (Dorthe), Caligo, M.A. (Maria), Laitman, Y. (Yael), Milgrom, R. (Roni), Kaufman, B. (Bella), Paluch-Shimon, S. (Shani), Friedman, E. (Eitan), Loman, N. (Niklas), Harbst, K. (Katja), Lindblom, A. (Annika), Melin, B. (Beatrice), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Cajal, T.R., Fostira, F. (Florentia), Andres, R. (Raquel), Benitez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Rookus, M.A. (Matti), Hooning, M.J. (Maartje), Nelen, M.R. (Marcel), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Asperen, C.J. (Christi) van, Devilee, P. (Peter), Meijers-Heijboer, H. (Hanne), Garcia, E.B.G., Peock, S. (Susan), Cook, M. (Margaret), Frost, D., Platte, R. (Radka), Leyland, J. (Jean), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Davidson, R. (Rosemarie), Eccles, D. (Diana), Ong, K.-R., Douglas, F. (Fiona), Paterson, J. (Joan), Kennedy, M.J. (John), Miedzybrodzka, Z. (Zosia), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Buecher, B. (Bruno), Belotti, M. (Muriel), Tirapo, C. (Carole), Mazoyer, S. (Sylvie), Barjhoux, L. (Laure), Lasset, C. (Christine), Leroux, D. (Dominique), Faivre, L. (Laurence), Bronner, M. (Myriam), Prieur, F. (Fabienne), Nogues, C. (Catherine), Rouleau, E. (Etienne), Pujol, P. (Pascal), Coupier, I. (Isabelle), Frenay, M. (Marc), Hopper, J. (John), Daly, M.J. (Mark), Terry, M-B. (Mary-beth), John, E.M. (Esther), Buys, S.S. (Saundra), Yassin, Y. (Yosuf), Miron, A. (Alexander), Goldgar, D. (David), Singer, C.F. (Christian), Tea, M.-K., Pfeiler, G. (Georg), Dressler, C. (Catherina), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Ejlertsen, B. (Bent), Barkardottir, R.B. (Rosa), Kircchoff, T. (Tomas), Offit, K. (Kenneth), Piedmonte, M. (Marion), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Boggess, J.F. (John), Blank, S.V. (Stephanie), Basil, J. (Jack), Azodi, M. (Masoud), Toland, A.E. (Amanda), Montagna, M. (Marco), Tognazzo, S. (Silvia), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Pharoah, P.D.P. (Paul), Sucheston, L. (Lara), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E. (Edith), Bozsik, A. (Aniko), Teo, S.-H. (Soo-Hwang), Seldon, J.L. (Joyce), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Sluiter, M.D. (Michelle), Diez, O. (Orland), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ruehl, I. (Ina), Varon-Mateeva, R. (Raymonda), Kast, K. (Karin), Deissler, H. (Helmut), Niederacher, D. (Dieter), Arnold, N. (Norbert), Gadzicki, D. (Dorothea), Schönbuchner, I. (Ines), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Dumont, M. (Martine), Chiquette, J. (Jocelyne), Tischkowitz, M. (Marc), Chenevix-Trench, G. (Georgia), Beesley, J. (Jonathan), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Fredericksen, Z. (Zachary), Wang, X. (Xing), Pankratz, V.S. (Shane), Couch, F.J. (Fergus), Simard, J. (Jacques), Easton, D.F. (Douglas), Karlsson, P. (Per), Nordling, M. (Margareta), Bergman, A. (Annika), Einbeigi, Z. (Zakaria), Stenmark-Askmalm, M. (M.), Liedgren, S. (Sigrun), Borg, Å. (Åke), Olsson, H. (Hans), Kristoffersson, U. (Ulf), Jernström, H. (H.), Henriksson, K. (Karin), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Barbany-Bustinza, G. (Gisela), Rantala, J. (Johanna), Grönberg, H. (Henrik), Stattin, E.-L., Emanuelsson, M. (Monica), Brandell, R.R., Dahl, N. (Niklas), Verhoef, S., Verheus, M. (Martijn), Veer, L.J. (Laura) van 't, Leeuwen, F.E. (Flora) van, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Jager, A. (Agnes), Tilanus-Linthorst, M.M.A. (Madeleine), Seynaeve, C.M. (Caroline), Wijnen, J.T. (Juul), Vreeswijk, M.P. (Maaike), Tollenaar, R.A.E.M. (Rob), Ligtenberg, M.J. (Marjolijn), Hoogerbrugge, N. (Nicoline), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Gille, J.J.P. (Jan), Waisfisz, Q. (Quinten), Gómez García, E.B. (Encarna), Roozendaal, C.E. (Cees) van, Blok, M.J. (Marinus), Caanen, B., Oosterwijk, J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J., Vasen, H.F. (Hans), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), McKeown, C. (Carole), Hoffman, J. (Jonathan), Donaldson, A. (Alan), Downing, S. (Sarah), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Hill, K. (Kathryn), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Whaite, A. (Anna), Dorkins, H. (Huw), Barwell, J. (Julian), Chu, C. (Chengbin), Miller, J. (Julie), Ellis, I.O. (Ian), Houghton, C. (Catherine), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), D'Mello, L. (Lucia), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Mitra, A. (Anita), Robertson, L. (Lisa), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Ehrencrona, H. (Hans), Hodgson, S.V. (Shirley), Barton, D.E. (David), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lucassen, A. (Anneke), Crawford, G. (Gillian), McBride, D. (Donna), Smalley, S. (Sarah), Adlard, J.W. (Julian), Arver, B. (Brita Wasteson), Antoniou, A.C. (Antonis), Kartsonaki, C. (Christiana), Sinilnikova, O. (Olga), Soucy, P. (Penny), McGuffog, L. (Lesley), Healey, S. (Sue), Lee, A. (Andrew), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Cattaneo, E. (Elisa), Barile, M. (Monica), Pensotti, V. (Valeria), Pasini, B. (Barbara), Dolcetti, R. (Riccardo), Giannini, G. (Giuseppe), Putignano, A.L., Varesco, L. (Liliana), Radice, P. (Paolo), Mai, P.L. (Phuong), Greene, M.H. (Mark), Andrulis, I.L. (Irene), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Kruse, T.A. (Torben), Jensen, U.B., Cruger, D. (Dorthe), Caligo, M.A. (Maria), Laitman, Y. (Yael), Milgrom, R. (Roni), Kaufman, B. (Bella), Paluch-Shimon, S. (Shani), Friedman, E. (Eitan), Loman, N. (Niklas), Harbst, K. (Katja), Lindblom, A. (Annika), Melin, B. (Beatrice), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Jakubowska, A. (Anna), Lubinski, J. (Jan), Gronwald, J. (Jacek), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Cybulski, C. (Cezary), Górski, B. (Bohdan), Osorio, A. (Ana), Cajal, T.R., Fostira, F. (Florentia), Andres, R. (Raquel), Benitez, J. (Javier), Hamann, U. (Ute), Hogervorst, F.B.L. (Frans), Rookus, M.A. (Matti), Hooning, M.J. (Maartje), Nelen, M.R. (Marcel), Luijt, R.B. (Rob) van der, Os, T.A.M. (Theo) van, Asperen, C.J. (Christi) van, Devilee, P. (Peter), Meijers-Heijboer, H. (Hanne), Garcia, E.B.G., Peock, S. (Susan), Cook, M. (Margaret), Frost, D., Platte, R. (Radka), Leyland, J. (Jean), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Davidson, R. (Rosemarie), Eccles, D. (Diana), Ong, K.-R., Douglas, F. (Fiona), Paterson, J. (Joan), Kennedy, M.J. (John), Miedzybrodzka, Z. (Zosia), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Buecher, B. (Bruno), Belotti, M. (Muriel), Tirapo, C. (Carole), Mazoyer, S. (Sylvie), Barjhoux, L. (Laure), Lasset, C. (Christine), Leroux, D. (Dominique), Faivre, L. (Laurence), Bronner, M. (Myriam), Prieur, F. (Fabienne), Nogues, C. (Catherine), Rouleau, E. (Etienne), Pujol, P. (Pascal), Coupier, I. (Isabelle), Frenay, M. (Marc), Hopper, J. (John), Daly, M.J. (Mark), Terry, M-B. (Mary-beth), John, E.M. (Esther), Buys, S.S. (Saundra), Yassin, Y. (Yosuf), Miron, A. (Alexander), Goldgar, D. (David), Singer, C.F. (Christian), Tea, M.-K., Pfeiler, G. (Georg), Dressler, C. (Catherina), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Ejlertsen, B. (Bent), Barkardottir, R.B. (Rosa), Kircchoff, T. (Tomas), Offit, K. (Kenneth), Piedmonte, M. (Marion), Rodriguez, G.C. (Gustavo), Small, L. (Laurie), Boggess, J.F. (John), Blank, S.V. (Stephanie), Basil, J. (Jack), Azodi, M. (Masoud), Toland, A.E. (Amanda), Montagna, M. (Marco), Tognazzo, S. (Silvia), Agata, S. (Simona), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Pharoah, P.D.P. (Paul), Sucheston, L. (Lara), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Olah, E. (Edith), Bozsik, A. (Aniko), Teo, S.-H. (Soo-Hwang), Seldon, J.L. (Joyce), Beattie, M.S. (Mary), Rensburg, E.J. (Elizabeth) van, Sluiter, M.D. (Michelle), Diez, O. (Orland), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Engel, C. (Christoph), Meindl, A. (Alfons), Ruehl, I. (Ina), Varon-Mateeva, R. (Raymonda), Kast, K. (Karin), Deissler, H. (Helmut), Niederacher, D. (Dieter), Arnold, N. (Norbert), Gadzicki, D. (Dorothea), Schönbuchner, I. (Ines), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Dumont, M. (Martine), Chiquette, J. (Jocelyne), Tischkowitz, M. (Marc), Chenevix-Trench, G. (Georgia), Beesley, J. (Jonathan), Spurdle, A.B. (Amanda), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Fredericksen, Z. (Zachary), Wang, X. (Xing), Pankratz, V.S. (Shane), Couch, F.J. (Fergus), Simard, J. (Jacques), Easton, D.F. (Douglas), Karlsson, P. (Per), Nordling, M. (Margareta), Bergman, A. (Annika), Einbeigi, Z. (Zakaria), Stenmark-Askmalm, M. (M.), Liedgren, S. (Sigrun), Borg, Å. (Åke), Olsson, H. (Hans), Kristoffersson, U. (Ulf), Jernström, H. (H.), Henriksson, K. (Karin), Wachenfeldt, A. (Anna) von, Liljegren, A. (Annelie), Barbany-Bustinza, G. (Gisela), Rantala, J. (Johanna), Grönberg, H. (Henrik), Stattin, E.-L., Emanuelsson, M. (Monica), Brandell, R.R., Dahl, N. (Niklas), Verhoef, S., Verheus, M. (Martijn), Veer, L.J. (Laura) van 't, Leeuwen, F.E. (Flora) van, Collée, J.M. (Margriet), Ouweland, A.M.W. (Ans) van den, Jager, A. (Agnes), Tilanus-Linthorst, M.M.A. (Madeleine), Seynaeve, C.M. (Caroline), Wijnen, J.T. (Juul), Vreeswijk, M.P. (Maaike), Tollenaar, R.A.E.M. (Rob), Ligtenberg, M.J. (Marjolijn), Hoogerbrugge, N. (Nicoline), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Gille, J.J.P. (Jan), Waisfisz, Q. (Quinten), Gómez García, E.B. (Encarna), Roozendaal, C.E. (Cees) van, Blok, M.J. (Marinus), Caanen, B., Oosterwijk, J.C., Hout, A.H. (Annemarie) van der, Mourits, M.J., Vasen, H.F. (Hans), Gregory, H. (Helen), Morrison, P.J. (Patrick), Jeffers, L. (Lisa), Cole, T.J. (Trevor), McKeown, C. (Carole), Hoffman, J. (Jonathan), Donaldson, A. (Alan), Downing, S. (Sarah), Taylor, A. (Amy), Murray, A. (Alexandra), Rogers, M.T. (Mark), McCann, E. (Emma), Porteous, M.E. (Mary), Drummond, S. (Sarah), Brewer, C. (Carole), Kivuva, E. (Emma), Searle, A. (Anne), Goodman, S. (Selina), Hill, K. (Kathryn), Murday, V. (Victoria), Bradshaw, N. (Nicola), Snadden, L. (Lesley), Longmuir, M. (Mark), Watt, C. (Catherine), Gibson, S. (Sarah), Haque, E. (Eshika), Tobias, E. (Ed), Duncan, A. (Alexis), Jacobs, C. (Chris), Langman, C. (Caroline), Whaite, A. (Anna), Dorkins, H. (Huw), Barwell, J. (Julian), Chu, C. (Chengbin), Miller, J. (Julie), Ellis, I.O. (Ian), Houghton, C. (Catherine), Side, L. (Lucy), Male, A. (Alison), Berlin, C. (Cheryl), Eason, J. (Jacqueline), Collier, R. (Rebecca), Claber, O. (Oonagh), Jobson, I. (Irene), Walker, L.J. (Lisa), McLeod, D. (Diane), Halliday, D. (Dorothy), Durell, S. (Sarah), Stayner, B. (Barbara), Shanley, S. (Susan), Rahman, N. (Nazneen), Houlston, R. (Richard), Bancroft, E.K. (Elizabeth), D'Mello, L. (Lucia), Page, E. (Elizabeth), Ardern-Jones, A. (Audrey), Kohut, K. (Kelly), Wiggins, J. (Jennifer), Castro, E. (Elena), Mitra, A. (Anita), Robertson, L. (Lisa), Quarrell, O. (Oliver), Bardsley, C. (Cathryn), Ehrencrona, H. (Hans), Hodgson, S.V. (Shirley), Barton, D.E. (David), Goff, S. (Sheila), Brice, G. (Glen), Winchester, L. (Lizzie), Eddy, C. (Charlotte), Tripathi, V. (Vishakha), Attard, V. (Virginia), Lucassen, A. (Anneke), Crawford, G. (Gillian), McBride, D. (Donna), Smalley, S. (Sarah), Adlard, J.W. (Julian), and Arver, B. (Brita Wasteson)
Abstract: Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r2= 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10-9for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10-8for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.
Published: 2011
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34. Evaluation of the XRCC1 gene as a phenotypic modifier in BRCA1/2 mutation carriers. Results from the consortium of investigators of modifiers of BRCA1/BRCA2

Author: Osorio, A. (Ana), Milne, R.L. (Roger), Pallás-Alonso, C.R. (Carmen), Pita, G. (Guillermo), Peterlongo, P. (Paolo), Teulé, A. (A.), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Lasa, A. (Adriana), Konstantopoulou, I. (I.), Hogervorst, F.B.L. (Frans), Verhoef, S. (Senno), Dooren, M.F. (Marieke) van, Jager, A. (Agnes), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Asperen, C.J. (Christi) van, Vreeswijk, M.P. (Maaike), Waisfisz, Q. (Quinten), Roozendaal, C.E.P. (Cornelis) van, Ligtenberg, M.J. (Marjolijn), Easton, D.F. (Douglas), Peock, S. (Susan), Cook, M.S. (Matthew), Oliver, C.T. (C. T.), Frost, D. (Debra), Curzon, B. (B.), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Davidson, R. (Rosemarie), Adlard, J.W. (Julian), Eccles, D. (Diana), Ong, K.-R. (Kai-Ren), Douglas, F. (Fiona), Downing, S. (S.), Brewer, C. (C.), Walker, L.J. (Lisa), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Couch, F.J. (Fergus), Fredericksen, Z. (Zachary), Lindor, N.M. (Noralane), Godwin, A.K. (Andrew), Isaacs, C. (Claudine), Caligo, M.A. (Maria), Loman, N. (Niklas), Jernström, H. (H.), Barbany-Bustinza, G. (Gisela), Liljegren, A. (Annelie), Ehrencrona, H. (Hans), Stenmark-Askmalm, M. (M.), Feliubadaló, L. (L.), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Bonnani, B. (Bernardo), Fortuzzi, S. (S.), Johannson, O.T. (Oskar), Chenevix-Trench, G. (Georgia), Chen, X.C. (X. C.), Beesley, J. (Jonathan), Spurdle, A.B. (Amanda), Sinilnikova, O. (Olga), Healey, S. (Sue), McGuffog, L. (Lesley), Antoniou, A.C. (Antonis), Brunet, J. (Joan), Radice, P. (Paolo), Benítez, J. (Javier), Osorio, A. (Ana), Milne, R.L. (Roger), Pallás-Alonso, C.R. (Carmen), Pita, G. (Guillermo), Peterlongo, P. (Paolo), Teulé, A. (A.), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Rebbeck, R. (Timothy), Lasa, A. (Adriana), Konstantopoulou, I. (I.), Hogervorst, F.B.L. (Frans), Verhoef, S. (Senno), Dooren, M.F. (Marieke) van, Jager, A. (Agnes), Ausems, M.G.E.M. (Margreet), Aalfs, C.M. (Cora), Asperen, C.J. (Christi) van, Vreeswijk, M.P. (Maaike), Waisfisz, Q. (Quinten), Roozendaal, C.E.P. (Cornelis) van, Ligtenberg, M.J. (Marjolijn), Easton, D.F. (Douglas), Peock, S. (Susan), Cook, M.S. (Matthew), Oliver, C.T. (C. T.), Frost, D. (Debra), Curzon, B. (B.), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Davidson, R. (Rosemarie), Adlard, J.W. (Julian), Eccles, D. (Diana), Ong, K.-R. (Kai-Ren), Douglas, F. (Fiona), Downing, S. (S.), Brewer, C. (C.), Walker, L.J. (Lisa), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Couch, F.J. (Fergus), Fredericksen, Z. (Zachary), Lindor, N.M. (Noralane), Godwin, A.K. (Andrew), Isaacs, C. (Claudine), Caligo, M.A. (Maria), Loman, N. (Niklas), Jernström, H. (H.), Barbany-Bustinza, G. (Gisela), Liljegren, A. (Annelie), Ehrencrona, H. (Hans), Stenmark-Askmalm, M. (M.), Feliubadaló, L. (L.), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Bonnani, B. (Bernardo), Fortuzzi, S. (S.), Johannson, O.T. (Oskar), Chenevix-Trench, G. (Georgia), Chen, X.C. (X. C.), Beesley, J. (Jonathan), Spurdle, A.B. (Amanda), Sinilnikova, O. (Olga), Healey, S. (Sue), McGuffog, L. (Lesley), Antoniou, A.C. (Antonis), Brunet, J. (Joan), Radice, P. (Paolo), and Benítez, J. (Javier)
Abstract: Background: Single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair are good candidates to be tested as phenotypic modifiers for carriers of mutations in the high-risk susceptibility genes BRCA1 and BRCA2. The base excision repair (BER) pathway could be particularly interesting given the relation of synthetic lethality that exists between one of the components of the pathway, PARP1, and both BRCA1 and BRCA2. In this study, we have evaluated the XRCC1 gene that participates in the BER pathway, as phenotypic modifier of BRCA1 and BRCA2. Methods: Three common SNPs in the gene, c.-77C>T (rs3213245) p.Arg280His (rs25489) and p.Gln399Arg (rs25487) were analysed in a series of 701 BRCA1 and 576 BRCA2 mutation carriers. Results: An association was observed between p.Arg280His-rs25489 and breast cancer risk for BRCA2 mutation carriers, with rare homozygotes at increased risk relative to common homozygotes (hazard ratio: 22.3, 95% confidence interval: 14.3-34, P<0.001). This association was further tested in a second series of 4480 BRCA1 and 3016 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2.Conclusions and inteNo evidence of association was found when the larger series was analysed which lead us to conclude that none of the three SNPs are significant modifiers of breast cancer risk for mutation carriers.
Published: 2011
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35. Exploring the link between MORF4L1 and risk of breast cancer

Author: Martrat, G. (Griselda), Maxwell, C.A. (Christopher), Tominaga, E. (Emiko), Porta-de-la-Riva, M. (Montserrat), Bonifaci, N. (Núria), Gómez-Baldó, L. (Laia), Bogliolo, M. (Massimo), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Brunet, J. (Joan), Aguilar, H. (Helena), Fernández-Rodríguez, J. (Juana), Seal, S. (Sheila), Renwick, A. (Anthony), Rahman, N. (Nazneen), Kühl, J. (Julia), Neveling, K. (Kornelia), Schindler, D. (Detlev), Ramírez, M.J. (María), Castellà, M. (María), Hernández, G. (Gonzalo), Easton, D.F. (Douglas), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Platte, R. (Radka), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Chu, C. (Chengbin), Davidson, R. (Rosemarie), Ong, K., Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Brewer, C. (Carole), Morrison, P.J. (Patrick), Porteous, M.E. (Mary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (Daniela), Roversi, G. (Gaia), Barile, M. (Monica), Viel, A. (Alessandra), Pasini, B. (Barbara), Ottini, L. (Laura), Putignano, A.L., Savarese, A. (Antonella), Bernard, L. (Loris), Radice, P. (Paolo), Healey, S. (Sue), Spurdle, A.B. (Amanda), Chen, X. (Xiaoqing), Beesley, J. (Jonathan), Rookus, M.A. (Matti), Verhoef, S., Tilanus-Linthorst, M.M.A. (Madeleine), Vreeswijk, M.P. (Maaike), Bodmer, D. (Danielle), Ausems, M.G.E.M. (Margreet), Os, T.A.M. (Theo) van, Blok, M.J. (Marinus), Meijers-Heijboer, E.J. (Hanne), Hogervorst, F.B.L. (Frans), Goldgar, D. (David), Buys, S.S. (Saundra), John, E.M. (Esther), Miron, A. (Alexander), Southey, M.C. (Melissa), Daly, M.J. (Mark), Harbst, K. (Katja), Borg, Å. (Åke), Rantala, J. (Johanna), Barbany-Bustinza, G. (Gisela), Ehrencrona, H. (Hans), Stenmark-Askmalm, M. (M.), Kaufman, B. (Bella), Laitman, Y. (Yael), Milgrom, R. (Roni), Friedman, E. (Eitan), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Johannson, O.T. (Oskar), Couch, F.J. (Fergus), Wang, X. (Xing), Fredericksen, Z. (Zachary), Cuadras, D. (Daniel), Moreno, V. (Víctor), Pientka, F.K. (Friederike), Depping, R. (Reinhard), Caldes, T. (Trinidad), Osorio, A. (Ana), Benítez, J. (Javier), Bueren, J. (Juan), Heikinen, T. (Tuomas), Nevanlinna, H. (Heli), Hamann, U. (Ute), Torres, D. (Diana), Caligo, M.A. (Maria), Godwin, A.K. (Andrew), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Sinilnikova, O. (Olga), Stoppa-Lyonnet, D. (Dominique), Mazoyer, S. (Sylvie), Verny-Pierre, C. (Carole), Castera, L. (Laurent), Pauw, A. (Antoine) de, Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Peyrat, J.-P., Vennin, P. (Philippe), Ferrer, S.F., Collonge-Rame, M.-A., Mortemousque, I. (Isabelle), McGuffog, L. (Lesley), Chenevix-Trench, G. (Georgia), Pereira-Smith, O.M. (Olivia), Antoniou, A.C. (Antonis), Cerón, J. (Julián), Surrallés, J. (Jordi), Pujana, M.A. (Miguel), Asperen, C.J. (Christi) van, Martrat, G. (Griselda), Maxwell, C.A. (Christopher), Tominaga, E. (Emiko), Porta-de-la-Riva, M. (Montserrat), Bonifaci, N. (Núria), Gómez-Baldó, L. (Laia), Bogliolo, M. (Massimo), Lázaro, C. (Conxi), Blanco, I. (Ignacio), Brunet, J. (Joan), Aguilar, H. (Helena), Fernández-Rodríguez, J. (Juana), Seal, S. (Sheila), Renwick, A. (Anthony), Rahman, N. (Nazneen), Kühl, J. (Julia), Neveling, K. (Kornelia), Schindler, D. (Detlev), Ramírez, M.J. (María), Castellà, M. (María), Hernández, G. (Gonzalo), Easton, D.F. (Douglas), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Platte, R. (Radka), Evans, D.G. (Gareth), Lalloo, F. (Fiona), Eeles, R. (Rosalind), Izatt, L. (Louise), Chu, C. (Chengbin), Davidson, R. (Rosemarie), Ong, K., Douglas, F. (Fiona), Hodgson, S.V. (Shirley), Brewer, C. (Carole), Morrison, P.J. (Patrick), Porteous, M.E. (Mary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (Daniela), Roversi, G. (Gaia), Barile, M. (Monica), Viel, A. (Alessandra), Pasini, B. (Barbara), Ottini, L. (Laura), Putignano, A.L., Savarese, A. (Antonella), Bernard, L. (Loris), Radice, P. (Paolo), Healey, S. (Sue), Spurdle, A.B. (Amanda), Chen, X. (Xiaoqing), Beesley, J. (Jonathan), Rookus, M.A. (Matti), Verhoef, S., Tilanus-Linthorst, M.M.A. (Madeleine), Vreeswijk, M.P. (Maaike), Bodmer, D. (Danielle), Ausems, M.G.E.M. (Margreet), Os, T.A.M. (Theo) van, Blok, M.J. (Marinus), Meijers-Heijboer, E.J. (Hanne), Hogervorst, F.B.L. (Frans), Goldgar, D. (David), Buys, S.S. (Saundra), John, E.M. (Esther), Miron, A. (Alexander), Southey, M.C. (Melissa), Daly, M.J. (Mark), Harbst, K. (Katja), Borg, Å. (Åke), Rantala, J. (Johanna), Barbany-Bustinza, G. (Gisela), Ehrencrona, H. (Hans), Stenmark-Askmalm, M. (M.), Kaufman, B. (Bella), Laitman, Y. (Yael), Milgrom, R. (Roni), Friedman, E. (Eitan), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Johannson, O.T. (Oskar), Couch, F.J. (Fergus), Wang, X. (Xing), Fredericksen, Z. (Zachary), Cuadras, D. (Daniel), Moreno, V. (Víctor), Pientka, F.K. (Friederike), Depping, R. (Reinhard), Caldes, T. (Trinidad), Osorio, A. (Ana), Benítez, J. (Javier), Bueren, J. (Juan), Heikinen, T. (Tuomas), Nevanlinna, H. (Heli), Hamann, U. (Ute), Torres, D. (Diana), Caligo, M.A. (Maria), Godwin, A.K. (Andrew), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Sinilnikova, O. (Olga), Stoppa-Lyonnet, D. (Dominique), Mazoyer, S. (Sylvie), Verny-Pierre, C. (Carole), Castera, L. (Laurent), Pauw, A. (Antoine) de, Bignon, Y.-J. (Yves-Jean), Uhrhammer, N. (Nancy), Peyrat, J.-P., Vennin, P. (Philippe), Ferrer, S.F., Collonge-Rame, M.-A., Mortemousque, I. (Isabelle), McGuffog, L. (Lesley), Chenevix-Trench, G. (Georgia), Pereira-Smith, O.M. (Olivia), Antoniou, A.C. (Antonis), Cerón, J. (Julián), Surrallés, J. (Jordi), Pujana, M.A. (Miguel), and Asperen, C.J. (Christi) van
Abstract: Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens.Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were perform
Published: 2011
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36. Genetic variation at 9p22.2 and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers

Author: Ramus, S.J. (Susan), Kartsonaki, C. (Christiana), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Sinilnikova, O. (Olga), Beesley, J. (Jonathan), Chenevix-Trench, G. (Georgia), McGuffog, L. (Lesley), Healey, S. (Sue), Couch, F.J. (Fergus), Wang, X. (Xing), Fredericksen, Z. (Zachary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Roversi, G. (Gaia), Barile, M. (Monica), Viel, A. (Alessandra), Allavena, A. (Anna), Ottini, L. (Laura), Papi, L. (Laura), Gismondi, V. (Viviana), Capra, F. (Fabio), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Andrulis, I.L. (Irene), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Kruse, T.A. (Torben), Cruger, D. (Dorthe), Jensen, U.B., Caligo, M.A. (Maria), Olsson, H. (Hkan), Kristoffersson, U. (Ulf), Lindblom, A. (Annika), Arver, B. (Brita Wasteson), Karlsson, P. (Per), Stenmark-Askmalm, M. (M.), Borg, Å. (Åke), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Górski, B. (Bohdan), Cybulski, C. (Cezary), Dbniak, T. (Tadeusz), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.-I., Benitez, J. (Javier), Hamann, U. (Ute), Rookus, M.A. (Matti), Verhoef, S., Tilanus-Linthorst, M.M.A. (Madeleine), Vreeswijk, M.P. (Maaike), Bodmer, D. (Danielle), Ausems, M.G.E.M. (Margreet), Os, T.A.M. (Theo) van, Blok, M.J. (Marinus), Meijers-Heijboer, H. (Hanne), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Dunning, A.M. (Alison), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Pichert, G. (Gabriella), Cole, T.J. (Trevor), Hodgson, S.V. (Shirley), Brewer, C. (Carole), Morrison, P.J. (Patrick), Porteous, M.E. (Mary), Kennedy, M.J. (John), Rogers, M.T. (Mark), Side, L. (Lucy), Donaldson, A. (Alan), Gregory, H. (Helen), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Moncoutier, V. (Virginie), Castera, L. (Laurent), Mazoyer, S. (Sylvie), Barjhoux, L. (Laure), Bonadona, V. (Valérie), Leroux, D. (Dominique), Faivre, L. (Laurence), Lidereau, R. (Rosette), Nogues, C. (Catherine), Bignon, Y.-J. (Yves-Jean), Prieur, F. (Fabienne), Collonge-Rame, M.-A., Vénat-Bouvet, L. (Laurence), Fert-Ferrer, S. (Sandra), Miron, A. (Alexander), Buys, S.S. (Saundra), Hopper, J. (John), Daly, M.J. (Mark), John, E.M. (Esther), Terry, M-B. (Mary-beth), Goldgar, D. (David), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Agnarsson, B.A. (Bjarni), Offit, K. (Kenneth), Kircchoff, T. (Tomas), Vijai, J. (Joseph), Dutra-Clarke, A. (Ana), Przybylo, J.A. (Jennifer), Montagna, M. (Marco), Casella, C. (Cinzia), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Moysich, K.B. (Kirsten), Karlan, B.Y. (Beth), Gross, J. (Jenny), Beattie, M.S. (Mary), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Meindl, A. (Alfons), Ruehl, I. (Ina), Fiebig, B. (Britta), Sutter, C. (Christian), Arnold, N. (Norbert), Deissler, H. (Helmut), Varon-Mateeva, R. (Raymonda), Kast, K. (Karin), Niederacher, D. (Dieter), Gadzicki, D. (Dorothea), Ejlertsen, B. (Bent), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Simard, J. (Jacques), Soucy, P. (Penny), Spurdle, A.B. (Amanda), Holland, H. (Helene), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), Asperen, C.J. (Christi) van, Ramus, S.J. (Susan), Kartsonaki, C. (Christiana), Gayther, S.A. (Simon), Pharoah, P.D.P. (Paul), Sinilnikova, O. (Olga), Beesley, J. (Jonathan), Chenevix-Trench, G. (Georgia), McGuffog, L. (Lesley), Healey, S. (Sue), Couch, F.J. (Fergus), Wang, X. (Xing), Fredericksen, Z. (Zachary), Peterlongo, P. (Paolo), Manoukian, S. (Siranoush), Peissel, B. (Bernard), Zaffaroni, D. (D.), Roversi, G. (Gaia), Barile, M. (Monica), Viel, A. (Alessandra), Allavena, A. (Anna), Ottini, L. (Laura), Papi, L. (Laura), Gismondi, V. (Viviana), Capra, F. (Fabio), Radice, P. (Paolo), Greene, M.H. (Mark), Mai, P.L. (Phuong), Andrulis, I.L. (Irene), Glendon, G. (Gord), Ozcelik, H. (Hilmi), Thomassen, M. (Mads), Gerdes, A-M. (Anne-Marie), Kruse, T.A. (Torben), Cruger, D. (Dorthe), Jensen, U.B., Caligo, M.A. (Maria), Olsson, H. (Hkan), Kristoffersson, U. (Ulf), Lindblom, A. (Annika), Arver, B. (Brita Wasteson), Karlsson, P. (Per), Stenmark-Askmalm, M. (M.), Borg, Å. (Åke), Neuhausen, S.L. (Susan), Ding, Y.C. (Yuan), Nathanson, K.L. (Katherine), Domchek, S.M. (Susan), Jakubowska, A. (Anna), Lubinski, J. (Jan), Huzarski, T. (Tomasz), Byrski, T. (Tomasz), Gronwald, J. (Jacek), Górski, B. (Bohdan), Cybulski, C. (Cezary), Dbniak, T. (Tadeusz), Osorio, A. (Ana), Durán, M. (Mercedes), Tejada, M.-I., Benitez, J. (Javier), Hamann, U. (Ute), Rookus, M.A. (Matti), Verhoef, S., Tilanus-Linthorst, M.M.A. (Madeleine), Vreeswijk, M.P. (Maaike), Bodmer, D. (Danielle), Ausems, M.G.E.M. (Margreet), Os, T.A.M. (Theo) van, Blok, M.J. (Marinus), Meijers-Heijboer, H. (Hanne), Peock, S. (Susan), Cook, M. (Margaret), Oliver, C.T. (Clare), Frost, D. (Debra), Dunning, A.M. (Alison), Evans, D.G. (Gareth), Eeles, R. (Rosalind), Pichert, G. (Gabriella), Cole, T.J. (Trevor), Hodgson, S.V. (Shirley), Brewer, C. (Carole), Morrison, P.J. (Patrick), Porteous, M.E. (Mary), Kennedy, M.J. (John), Rogers, M.T. (Mark), Side, L. (Lucy), Donaldson, A. (Alan), Gregory, H. (Helen), Godwin, A.K. (Andrew), Stoppa-Lyonnet, D. (Dominique), Moncoutier, V. (Virginie), Castera, L. (Laurent), Mazoyer, S. (Sylvie), Barjhoux, L. (Laure), Bonadona, V. (Valérie), Leroux, D. (Dominique), Faivre, L. (Laurence), Lidereau, R. (Rosette), Nogues, C. (Catherine), Bignon, Y.-J. (Yves-Jean), Prieur, F. (Fabienne), Collonge-Rame, M.-A., Vénat-Bouvet, L. (Laurence), Fert-Ferrer, S. (Sandra), Miron, A. (Alexander), Buys, S.S. (Saundra), Hopper, J. (John), Daly, M.J. (Mark), John, E.M. (Esther), Terry, M-B. (Mary-beth), Goldgar, D. (David), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Agnarsson, B.A. (Bjarni), Offit, K. (Kenneth), Kircchoff, T. (Tomas), Vijai, J. (Joseph), Dutra-Clarke, A. (Ana), Przybylo, J.A. (Jennifer), Montagna, M. (Marco), Casella, C. (Cinzia), Imyanitov, E.N. (Evgeny), Janavicius, R. (Ramunas), Blanco, I. (Ignacio), Lázaro, C. (Conxi), Moysich, K.B. (Kirsten), Karlan, B.Y. (Beth), Gross, J. (Jenny), Beattie, M.S. (Mary), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Meindl, A. (Alfons), Ruehl, I. (Ina), Fiebig, B. (Britta), Sutter, C. (Christian), Arnold, N. (Norbert), Deissler, H. (Helmut), Varon-Mateeva, R. (Raymonda), Kast, K. (Karin), Niederacher, D. (Dieter), Gadzicki, D. (Dorothea), Ejlertsen, B. (Bent), Caldes, T. (Trinidad), Hoya, M. (Miguel) de La, Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Simard, J. (Jacques), Soucy, P. (Penny), Spurdle, A.B. (Amanda), Holland, H. (Helene), Easton, D.F. (Douglas), Antoniou, A.C. (Antonis), and Asperen, C.J. (Christi) van
Abstract: Background Germline mutations in the BRCA1 and BRCA2 genes are associated with increased risks of breast and ovarian cancers. Although several common variants have been associated with breast cancer susceptibility in mutation carriers, none have been associated with ovarian cancer susceptibility. A genome-wide association study recently identified an association between the rare allele of the single-nucleotide polymorphism (SNP) rs3814113 (ie, the C allele) at 9p22.2 and decreased risk of ovarian cancer for women in the general population. We evaluated the association of this SNP with ovarian cancer risk among BRCA1 or BRCA2 mutation carriers by use of data from the Consortium of Investigators of Modifiers of BRCA1/2. Method sWe genotyped rs3814113 in 10029 BRCA1 mutation carriers and 5837 BRCA2 mutation carriers. Associations with ovarian and breast cancer were assessed with a retrospective likelihood approach. All statistical tests were two-sided. Results The minor allele of rs3814113 was associated with a reduced risk of ovarian cancer among BRCA1 mutation carriers (per-allele hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.72 to 0.85; P = 4.8 × 10-9) and BRCA2 mutation carriers (hazard ratio of ovarian cancer = 0.78, 95% confidence interval = 0.67 to 0.90; P = 5.5 × 10-4). This SNP was not associated with breast cancer risk among either BRCA1 or BRCA2 mutation carriers. BRCA1 mutation carriers with the TT genotype at SNP rs3814113 were predicted to have an ovarian cancer risk to age 80 years of 48%, and those with the CC genotype were predicted to have a risk of 33%. Conclusion Common genetic variation at the 9p22.2 locus was associated with decreased risk of ovarian cancer for carriers of a BRCA1 or BRCA2 mutation.
Published: 2011
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37. Regular surveillance for Li-fraumeni syndrome: advice, adherence and perceived benefits

Author: Lammens, C.R.M. (Chantal), Bleiker, E.M.A. (Eveline), Aaronson, N.K. (Neil), Wagner, A. (Anja), Sijmons, R.H. (Rolf), Ausems, M.G.E.M. (Margreet), Vriends, A.H.J.T. (Anette), Ruijs, M.W.G. (Marielle), Os, T.A.M. (Theo) van, Spruijt, L. (Liesbeth), Gómez García, E.B. (Encarna), Cats, A. (Annemieke), Nagtegaal, T., Verhoef, S., Lammens, C.R.M. (Chantal), Bleiker, E.M.A. (Eveline), Aaronson, N.K. (Neil), Wagner, A. (Anja), Sijmons, R.H. (Rolf), Ausems, M.G.E.M. (Margreet), Vriends, A.H.J.T. (Anette), Ruijs, M.W.G. (Marielle), Os, T.A.M. (Theo) van, Spruijt, L. (Liesbeth), Gómez García, E.B. (Encarna), Cats, A. (Annemieke), Nagtegaal, T., and Verhoef, S.
Abstract: Li Fraumeni Syndrome (LFS) is a hereditary cancer syndrome characterized by a high risk of developing various types of cancer from birth through late adulthood. Clinical benefits of surveillance for LFS are limited. The aim of this study is to investigate which advice for regular surveillance, if any, is given to high risk LFS individuals, adherence to that advice, and any psychological gain or burden derived from surveillance. Fifty-five high risk individuals (proven carriers and those at 50% risk) from families with a p53 germline mutation were invited to participate, of whom 82% completed a self-report questionnaire assessing advice for regular surveillance, compliance, perceived benefits and barriers of screening and LFS-related distress (IES) and worries (CWS). In total, 71% of the high risk family members received advice to undergo regular surveillance for LFS. The majority (78%) reported adherence with the recommended advice. All high risk women aged 25 or older reported having been advised to undergo annual breast cancer surveillance (n = 11), of whom 64% (n = 7) in specific received advice to undergo a mammography. Seventy-eight percent of respondents indicated having received tailored surveillance advice based on family cancer history. The large majority of respondents believed in the value of surveillance to detect tumors at an early stage (90%) and reported that it gave them a sense of control (84%) and security (70%). Despite its limited clinical benefits, the majority of high risk LFS family are advised to undergo, and are adherent to, and report psychological benefit from, regular surveillance programs.
Published: 2010
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38. A method to assess the clinical significance of unclassified variants in the BRCA1 and BRCA2 genes based on cancer family history

Author: Gómez García, E.B. (Encarna), Oosterwijk, J.C. (Jan), Timmermans, M. (Maarten), Asperen, C.J. (Christi) van, Hogervorst, F.B.L. (Frans), Hoogerbrugge, N. (Nicoline), Oldenburg, R.A. (Rogier), Verhoef, S. (Senno), Dommering, C.J. (Charlotte), Ausems, M.G.E.M. (Margreet), Os, T.A.M. (Theo) van, Hout, A.H. (Annemarie) van der, Ligtenberg, M.J. (Marjolijn), Ouweland, A.M.W. (Ans) van den, Luijt, R.B. (Rob) van der, Wijnen, J.T. (Juul), Gille, J.J.P. (Jan), Lindsey, P.J. (Patrick), Devilee, P. (Peter), Blok, M.J. (Marinus), Vreeswijk, M.P. (Maaike), Gómez García, E.B. (Encarna), Oosterwijk, J.C. (Jan), Timmermans, M. (Maarten), Asperen, C.J. (Christi) van, Hogervorst, F.B.L. (Frans), Hoogerbrugge, N. (Nicoline), Oldenburg, R.A. (Rogier), Verhoef, S. (Senno), Dommering, C.J. (Charlotte), Ausems, M.G.E.M. (Margreet), Os, T.A.M. (Theo) van, Hout, A.H. (Annemarie) van der, Ligtenberg, M.J. (Marjolijn), Ouweland, A.M.W. (Ans) van den, Luijt, R.B. (Rob) van der, Wijnen, J.T. (Juul), Gille, J.J.P. (Jan), Lindsey, P.J. (Patrick), Devilee, P. (Peter), Blok, M.J. (Marinus), and Vreeswijk, M.P. (Maaike)
Abstract: Introduction: Unclassified variants (UVs) in the BRCA1/BRCA2 genes are a frequent problem in counseling breast cancer and/or ovarian cancer families. Information about cancer family history is usually available, but has rarely been used to evaluate UVs. The aim of the present study was to identify which is the best combination of clinical parameters that can predict whether a UV is deleterious, to be used for the classification of UVs.Methods: We developed logistic regression models with the best combination of clinical features that distinguished a positive control of BRCA pathogenic variants (115 families) from a negative control population of BRCA variants initially classified as UVs and later considered neutral (38 families).Results: The models included a combination of BRCAPRO scores, Myriad scores, number of ovarian cancers in the family, the age at diagnosis, and the number of persons with ovarian tumors and/or breast tumors. The areas under the receiver operating characteristic curves were respectively 0.935 and 0.836 for the BRCA1 and BRCA2 models. For each model, the minimum receiver operating characteristic distance (respectively 90% and 78% specificity for BRCA1 and BRCA2) was chosen as the cutoff value to predict which UVs are deleterious from a study population of 12 UVs, present in 59 Dutch families. The p.S1655F, p.R1699W, and p.R1699Q variants in BRCA1 and the p.Y2660D, p.R2784Q, and p.R3052W variants in BRCA2 are classified as deleterious according to our models. The predictions of the p.L246V variant in BRCA1 and of the p.Y42C, p.E462G, p.R2888C, and p.R3052Q variants in BRCA2 are in agreement with published information of them being neutral. The p.R2784W variant in BRCA2 remains uncertain.Conclusions: The present study shows that these developed models are useful to classify UVs in clinical genetic practice.
Published: 2009
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39. The contribution of CHEK2 to the TP53-negative Li-Fraumeni phenotype

Author: Ruijs, M.W.G. (Marielle), Broeks, A. (Annegien), Menko, F. (Fred), Ausems, M.G.E.M. (Margreet), Wagner, A. (Anja), Oldenburg, R.A. (Rogier), Meijers-Heijboer, H. (Hanne), Veer, L.J. (Laura) van 't, Verhoef, S. (Senno), Ruijs, M.W.G. (Marielle), Broeks, A. (Annegien), Menko, F. (Fred), Ausems, M.G.E.M. (Margreet), Wagner, A. (Anja), Oldenburg, R.A. (Rogier), Meijers-Heijboer, H. (Hanne), Veer, L.J. (Laura) van 't, and Verhoef, S. (Senno)
Abstract: Background: CHEK2 has previously been excluded as a major cause of Li-Fraumeni syndrome (LFS). One particular CHEK2 germline mutation, c.1100delC, has been shown to be associated with elevated breast cancer risk. The prevalence of CHEK21100delC differs between populations and has been found to be relatively high in the Netherlands. The question remains nevertheless whether CHEK2 germline mutations contribute to the Li-Fraumeni phenotype.Methods: We have screened 65 Dutch TP53-negative LFS/LFL candidate patients for CHEK2 germline mutations to determine their contribution to the LFS/LFL phenotype.Results: We identified six index patients with a CHEK2 sequence variant, four with the c.1100delC variant and two sequence variants of unknown significance, p.Phe328Ser and c.1096-?_1629+?del.Conclusion: Our data show that CHEK2 is not a major LFS susceptibility gene in the Dutch population. However, CHEK2 might be a factor contributing to individual tumour development in TP53-negative cancer-prone families.
Published: 2009
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40. Attitude towards pre-implantation genetic diagnosis for hereditary cancer

Author: Lammens, C.R.M. (Chantal), Bleiker, E.M.A. (Eveline), Aaronson, N.K. (Neil), Vriends, A.H.J.T. (Anette), Jansweijer, M. (Maaike), Ausems, M.G.E.M. (Margreet), Wagner, A. (Anja), Sijmons, R.H. (Rolf), Ouweland, A.M.W. (Ans) van den, Luijt, R.B. (Rob) van der, Spruijt, L. (Liesbeth), Verhoef, S. (Senno), Gómez García, E.B. (Encarna), Ruijs, M.W.G. (Marielle), Lammens, C.R.M. (Chantal), Bleiker, E.M.A. (Eveline), Aaronson, N.K. (Neil), Vriends, A.H.J.T. (Anette), Jansweijer, M. (Maaike), Ausems, M.G.E.M. (Margreet), Wagner, A. (Anja), Sijmons, R.H. (Rolf), Ouweland, A.M.W. (Ans) van den, Luijt, R.B. (Rob) van der, Spruijt, L. (Liesbeth), Verhoef, S. (Senno), Gómez García, E.B. (Encarna), and Ruijs, M.W.G. (Marielle)
Abstract: The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition. Forty-eight Von Hippel-Lindau and 18 Li-Fraumeni Syndrome families were identified via the 9 family cancer clinics in the Netherlands. In total, 216 high risk family members and partners were approached, of whom 179 (83%) completed a self-report questionnaire. Of the high risk family members, 35% expressed a positive attitude towards PGD. Those with a current desire to have children were significantly more likely to have a positive attitude: 48% would consider the use of PGD. No other sociodemographic, medical or psychosocial variables were associated significantly with a positive attitude. The most frequently reported advantage of PGD is the avoidance of a possible pregnancy termination. Uncertainty about late effects was the most frequently reported disadvantage. These results indicate that approximately half of those contemplating a future pregnancy would consider the use of PGD. The actual uptake, however, is expected to be lower. There is no indication that psychosocial fa
Published: 2009
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