Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer

Rebbeck, Timothy R.; Mitra, Nandita; Wan, Fei; Sinilnikova, Olga M.; Healey, Sue; Mcguffog, Lesley; Chenevix Trench, Georgia; Easton, Douglas F.; Antoniou, Antonis C.; Nathanson, Katherine L.; Laitman, Yael; Kushnir, Anya; Paluch Shimon, Shani; Berger, Raanan; Zidan, Jamal; Friedman, Eitan; Ehrencrona, Hans; Stenmark Askmalm, Marie; Einbeigi, Zakaria; Loman, Niklas; Harbst, Katja; Rantala, Johanna; Melin, Beatrice; Huo, Dezheng; Olopade, Olufunmilayo I.; Seldon, Joyce; Ganz, Patricia A.; Nussbaum, Robert L.; Chan, Salina B.; Odunsi, Kunle; Gayther, Simon A.; Domchek, Susan M.; Arun, Banu K.; Karen H., Lu; Mitchell, Gillian; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Godwin, Andrew K.; Pathak, Harsh; Ross, Eric; Daly, Mary B.; Whittemore, Alice S.; John, Esther M.; Miron, Alexander; Terry, Mary Beth; Chung, Wendy K.; Goldgar, David E.; Buys, Saundra S.; Janavičius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M.; Van Rensburg, Elizabeth J.; Steele, Linda; Neuhausen, Susan L.; Ding, Yuan Chun; Ejlertsen, Bent; Gerdes, Anne Marie; Hansen, Thomas V. O.; Ramon Y. Cajal, Teresa; Osorio, Ana; Benitez, Javier; Godino, Javier; Tejada, Maria Isabel; Duran, Mercedes; Weitzel, Jeffrey N.; Bobolis, Kristie A.; Sand, Sharon R.; Fontaine, Annette; Savarese, Antonella; Pasini, Barbara; Peissel, Bernard; Bonanni, Bernardo; Zaffaroni, Daniela; Vignolo Lutati, Francesca; Scuvera, Giulietta; Giannini, Giuseppe; Bernard, Loris; Genuardi, Maurizio; Radice, Paolo; Dolcetti, Riccardo; Manoukian, Siranoush; Pensotti, Valeria; Gismondi, Viviana; Yannoukakos, Drakoulis; Fostira, Florentia; Garber, Judy; Torres, Diana; Rashid, Muhammad Usman; Hamann, Ute; Peock, Susan; Frost, Debra; Platte, Radka; Evans, D. Gareth; Eeles, Rosalind; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Izatt, Louise; Adlard, Julian; Donaldson, Alan; Ellis, Steve; Sharma, Priyanka; Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Becker, Alexandra; Rhiem, Kerstin; Hahnen, Eric; Engel, Christoph; Meindl, Alfons; Engert, Stefanie; Ditsch, Nina; Arnold, Norbert; Plendl, Hans Jorg; Mundhenke, Christoph; Niederacher, Dieter; Fleisch, Markus; Sutter, Christian; Bartram, C. R.; Dikow, Nicola; Wang Gohrke, Shan; Gadzicki, Dorothea; Steinemann, Doris; Kast, Karin; Beer, Marit; Varon Mateeva, Raymonda; Gehrig, Andrea; Weber, Bernhard H.; Stoppa Lyonnet, Dominique; Belotti, Muriel; Gauthier Villars, Marion; Damiola, Francesca; Boutry Kryza, Nadia; Lasset, Christine; Sobol, Hagay; Peyrat, Jean Philippe; Muller, Daniele; Fricker, Jean Pierre; Collonge Rame, Marie Agnes; Mortemousque, Isabelle; Nogues, Catherine; Rouleau, Etienne; Isaacs, Claudine; De Paepe, Anne; Poppe, Bruce; Claes, Kathleen; De Leeneer, Kim; Piedmonte, Marion; Rodriguez, Gustavo; Wakely, Katie; Boggess, John; Blank, Stephanie V.; Basil, Jack; Azodi, Masoud; Phillips, Kelly Anne; Caldes, Trinidad; De La Hoya, Miguel; Romero, Atocha; Nevanlinna, Heli; Aittomaki, Kristiina; Van Der Hout, Annemarie H.; Hogervorst, Frans B. L.; Verhoef, Senno; Collee, J. Margriet; Seynaeve, Caroline; Oosterwijk, Jan C.; Gille, Johannes J. P.; Wijnen, Juul T.; Gomez Garcia, Encarna B.; Kets, Carolien M.; Ausems, Margreet G. E. M.; Aalfs, Cora M.; Devilee, Peter; Mensenkamp, Arjen R.; Kwong, Ava; Olah, Edith; Papp, Janos; Diez, Orland; Lazaro, Conxi; Darder, Esther; Blanco, Ignacio; Salinas, Monica; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Jaworska Bieniek, Katarzyna; Durda, Katarzyna; Sukiennicki, Grzegorz; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko Grabarek, Aleksandra; Złowocka Perłowska, Elzbieta; Menkiszak, Janusz; Arason, Adalgeir; Barkardottir, Rosa B.; Simard, Jacques; Laframboise, Rachel; Montagna, Marco; Agata, Simona; Alducci, Elisa; Peixoto, Ana; Teixeira, Manuel R.; Spurdle, Amanda B.; Lee, Min Hyuk; Park, Sue K.; Kim, Sung Won; Friebel, Tara M.; Couch, Fergus J.; Lindor, Noralane M.; Pankratz, Vernon S.; Guidugli, Lucia; Wang, Xianshu; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Robson, Mark; Rau Murthy, Rohini; Kauff, Noah; Fink Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Gschwantler Kaulich, Daphne; Pfeiler, Georg; Tea, Muy Kheng; Berger, Andreas; Greene, Mark H.; Mai, Phuong L.; Imyanitov, Evgeny N.; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Pedersen, Inge Sokilde; Skytte, Anne Bine; Sunde, Lone; Thomassen, Mads; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Caligo, Maria Adelaide; Aretini, Paolo; Teo, Soo Hwang; Selkirk, Christina G.; Hulick, Peter J.; Andrulis, Irene

doi:10.1001/jama.2014.5985

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

Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer / Rebbeck, Timothy R.; Mitra, Nandita; Wan, Fei; Sinilnikova, Olga M.; Healey, Sue; Mcguffog, Lesley; Chenevix Trench, Georgia; Easton, Douglas F.; Antoniou, Antonis C.; Nathanson, Katherine L.; Laitman, Yael; Kushnir, Anya; Paluch Shimon, Shani; Berger, Raanan; Zidan, Jamal; Friedman, Eitan; Ehrencrona, Hans; Stenmark Askmalm, Marie; Einbeigi, Zakaria; Loman, Niklas; Harbst, Katja; Rantala, Johanna; Melin, Beatrice; Huo, Dezheng; Olopade, Olufunmilayo I.; Seldon, Joyce; Ganz, Patricia A.; Nussbaum, Robert L.; Chan, Salina B.; Odunsi, Kunle; Gayther, Simon A.; Domchek, Susan M.; Arun, Banu K.; Lu, Karen H.; Mitchell, Gillian; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Godwin, Andrew K.; Pathak, Harsh; Ross, Eric; Daly, Mary B.; Whittemore, Alice S.; John, Esther M.; Miron, Alexander; Terry, Mary Beth; Chung, Wendy K.; Goldgar, David E.; Buys, Saundra S.; Janavičius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M.; Van Rensburg, Elizabeth J.; Steele, Linda; Neuhausen, Susan L.; Ding, Yuan Chun; Ejlertsen, Bent; Gerdes, Anne Marie; Hansen, Thomas V. O.; Ramon Y. Cajal, Teresa; Osorio, Ana; Benitez, Javier; Godino, Javier; Tejada, Maria Isabel; Duran, Mercedes; Weitzel, Jeffrey N.; Bobolis, Kristie A.; Sand, Sharon R.; Fontaine, Annette; Savarese, Antonella; Pasini, Barbara; Peissel, Bernard; Bonanni, Bernardo; Zaffaroni, Daniela; Vignolo Lutati, Francesca; Scuvera, Giulietta; Giannini, Giuseppe; Bernard, Loris; Genuardi, Maurizio; Radice, Paolo; Dolcetti, Riccardo; Manoukian, Siranoush; Pensotti, Valeria; Gismondi, Viviana; Yannoukakos, Drakoulis; Fostira, Florentia; Garber, Judy; Torres, Diana; Rashid, Muhammad Usman; Hamann, Ute; Peock, Susan; Frost, Debra; Platte, Radka; Evans, D. Gareth; Eeles, Rosalind; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Izatt, Louise; Adlard, Julian; Donaldson, Alan; Ellis, Steve; Sharma, Priyanka; Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Becker, Alexandra; Rhiem, Kerstin; Hahnen, Eric; Engel, Christoph; Meindl, Alfons; Engert, Stefanie; Ditsch, Nina; Arnold, Norbert; Plendl, Hans Jorg; Mundhenke, Christoph; Niederacher, Dieter; Fleisch, Markus; Sutter, Christian; Bartram, C. R.; Dikow, Nicola; Wang Gohrke, Shan; Gadzicki, Dorothea; Steinemann, Doris; Kast, Karin; Beer, Marit; Varon Mateeva, Raymonda; Gehrig, Andrea; Weber, Bernhard H.; Stoppa Lyonnet, Dominique; Belotti, Muriel; Gauthier Villars, Marion; Damiola, Francesca; Boutry Kryza, Nadia; Lasset, Christine; Sobol, Hagay; Peyrat, Jean Philippe; Muller, Daniele; Fricker, Jean Pierre; Collonge Rame, Marie Agnes; Mortemousque, Isabelle; Nogues, Catherine; Rouleau, Etienne; Isaacs, Claudine; De Paepe, Anne; Poppe, Bruce; Claes, Kathleen; De Leeneer, Kim; Piedmonte, Marion; Rodriguez, Gustavo; Wakely, Katie; Boggess, John; Blank, Stephanie V.; Basil, Jack; Azodi, Masoud; Phillips, Kelly Anne; Caldes, Trinidad; De La Hoya, Miguel; Romero, Atocha; Nevanlinna, Heli; Aittomaki, Kristiina; Van Der Hout, Annemarie H.; Hogervorst, Frans B. L.; Verhoef, Senno; Collee, J. Margriet; Seynaeve, Caroline; Oosterwijk, Jan C.; Gille, Johannes J. P.; Wijnen, Juul T.; Gomez Garcia, Encarna B.; Kets, Carolien M.; Ausems, Margreet G. E. M.; Aalfs, Cora M.; Devilee, Peter; Mensenkamp, Arjen R.; Kwong, Ava; Olah, Edith; Papp, Janos; Diez, Orland; Lazaro, Conxi; Darder, Esther; Blanco, Ignacio; Salinas, Monica; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Jaworska Bieniek, Katarzyna; Durda, Katarzyna; Sukiennicki, Grzegorz; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko Grabarek, Aleksandra; Złowocka Perłowska, Elzbieta; Menkiszak, Janusz; Arason, Adalgeir; Barkardottir, Rosa B.; Simard, Jacques; Laframboise, Rachel; Montagna, Marco; Agata, Simona; Alducci, Elisa; Peixoto, Ana; Teixeira, Manuel R.; Spurdle, Amanda B.; Lee, Min Hyuk; Park, Sue K.; Kim, Sung Won; Friebel, Tara M.; Couch, Fergus J.; Lindor, Noralane M.; Pankratz, Vernon S.; Guidugli, Lucia; Wang, Xianshu; Tischkowitz, Marc; Foretova, Lenka; Vijai, Joseph; Offit, Kenneth; Robson, Mark; Rau Murthy, Rohini; Kauff, Noah; Fink Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Gschwantler Kaulich, Daphne; Pfeiler, Georg; Tea, Muy Kheng; Berger, Andreas; Greene, Mark H.; Mai, Phuong L.; Imyanitov, Evgeny N.; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Pedersen, Inge Sokilde; Skytte, Anne Bine; Sunde, Lone; Thomassen, Mads; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Caligo, Maria Adelaide; Aretini, Paolo; Teo, Soo Hwang; Selkirk, Christina G.; Hulick, Peter J.; Andrulis, Irene. - In: JAMA. - ISSN 0098-7484. - STAMPA. - 313:13(2015), pp. 1347-1361. [10.1001/jama.2014.5985]