Genome-wide association study in BRCA1 mutation carriers identifies Novel Loci associated with breast and ovarian cancer risk (2024)

Dorfling, Cecilia Maria; Jansen van Rensburg, Elizabeth; Couch, Fergus J.; Wang, Xianshu; McGuffog, Lesley; Lee, Andrew; Olswold, Curtis; Kuchenbaecker, Karoline B.; Soucy, Penny; Fredericksen, Zachary; Barrowdale, Daniel; Dennis, Joe; Gaudet, Mia M.; Dicks, Ed; Kosel, Matthew; Healey, Sue; Sinilnikova, Olga M.; Lee, Adam; Bacot, Francois; Vincent, Daniel; Hogervorst, Frans B.L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Jakubowska, Anna; kConFab Investigators (Kathleen, Cuningham); Radice, Paolo; Schmutzler, Rita Katharina; Domchek, Susan M.; Piedmonte, Marion; Singer, Christian F.; Friedman, Eitan; Thomassen, Mads; Ontario Cancer Genetics Network; Hansen, Thomas V.O.; Neuhausen, Susan L.; Szabo, Csilla I.; Blanco, Ignacio; Greene, Mark H.; Karlan, Beth Y.; Garber, Judy; Phelan, Catherine M.; Weitzel, Jeffrey N.; Montagna, Marco; Olah, Edith; Andrulis, Irene L.; Godwin, Andrew K.; Yannoukakos, Drakoulis; Goldgar, David E.; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; Terry, Mary Beth; Daly, Mary B.; Hamann, Ute; Ramus, Susan J.; Toland, Amanda Ewart; Caligo, Maria A.; Olopade, Olufunmilayo I.; Tung, Nadine; Claes, Kathleen; Beattie, Mary S.; Southey, Melissa C.; Imyanitov, Evgeny N.; Tischkowitz, Marc; Janavicius, Ramunas; John, Esther M.; Kwong, Ava; Diez, Orland; Balmana, Judith; Barkardottir, Rosa B.; Arun, Banu K.; Rennert, Gad; Teo, Soo-Hwang; Ganz, Patricia A.; Campbell, Ian G.; Van der Hout, Annemarie H.; Van Deurzen, Carolien H.M.; Seynaeve, Caroline; Gomez Garcia, Encarna B.; Van Leeuwen, Flora E.; Meijers-Heijboer, Hanne E.J.; Gille, Johannes J.P.; Ausems, Margreet G.E.M.; Blok, Marinus J.; Ligtenberg, Marjolijn J.L.; Rookus, Matti A.; Devilee, Peter; Verhoef, Senno; Van Os, Theo A.M.; Wijnen, Juul T.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Izatt, Louise; Eeles, Rosalind A.; Adlard, Julian; Eccles, Diana M.; Cook, Jackie; Brewer, Carole; Douglas, Fiona; Hodgson, Shirley; Morrison, Patrick J.; Side, Lucy E.; Donaldson, Alan; Houghton, Catherine; Rogers, Mark T.; Dorkins, Huw; Eason, Jacqueline; Gregory, Helen; McCann, Emma; Calender, Alain; Hardouin, Agnes; Berthet, Pascaline; Delnatte, Capucine; Nogues, Catherine; Lasset, Christine; Houdayer, Claude; Leroux, Dominique; Rouleau, Etienne; Prieur, Fabienne; Damiola, Francesca; Sobol, Hagay; Coupier, Isabelle; Venat-Bouvet, Laurence; Castera, Laurent; Gauthier-Villars, Marion; Leone, Melanie; Pujol, Pascal; Mazoyer, Sylvie; Bignon, Yves-Jean; Złowocka-Perlowska, Elz bieta; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska, Katarzyna; Huzarski, Tomasz; Spurdle, Amanda B.; Viel, Alessandra; Peissel, Bernard; Bonanni, Bernardo; Melloni, Giulia; Ottini, Laura; Papi, Laura; Varesco, Liliana; Tibiletti, Maria Grazia; Peterlongo, Paolo; Volorio, Sara; Manoukian, Siranoush; Pensotti, Valeria; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Gadzicki, Dorothea; Gehrig, Andrea; Kast, Karin; Rhiem, Kerstin; Meindl, Alfons; Niederacher, Dieter; Ditsch, Nina; Plendl, Hansjoerg; Preisler-Adams, Sabine; Engert, Stefanie; Sutter, Christian; Varon-Mateeva, Raymonda; Wappenschmidt, Barbara; Weber, Bernhard H.F; Arver, Brita; Stenmark-Askmalm, Marie; Loman, Niklas; Rosenquist, Richard; Einbeigi, Zakaria; Nathanson, Katherine L.; Rebbeck, Timothy R.; Blank, Stephanie V.; Cohn, David E.; Rodriguez, Gustavo C.; Small, Laurie; Friedlander, Michael; Bae-Jump, Victoria L.; Fink-Retter, Anneliese; Rappaport, Christine; Gschwantler-Kaulich, Daphne; Pfeiler, Georg; Tea, Muy-Kheng M.; Lindor, Noralane M.; Kaufman, Bella; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Gerdes, Anne-Marie; Pedersen, Inge Sokilde; Moeller, Sanne Traasdahl; Kruse, Torben A.; Jensen, Uffe Birk; Vijai, Joseph; Sarrel, Kara; Robson, Mark; Kauff, Noah; Mulligan, Anna Marie; Glendon, Gord; Ozcelik, Hilmi; Ejlertsen, Bent; Nielsen, Finn C.; Jonson, Lars; Andersen, Mette K.; Ding, Yuan Chun; Steele, Linda; Foretova, Lenka; Teule, Alex; Lazaro, Conxi; Brunet, Joan; Pujana, Miquel Angel; Mai, Phuong L.; Loud, Jennifer T.; Walsh, Christine; Lester, Jenny; Orsulic, Sandra; Narod, Steven A.; Herzog, Josef; Sand, Sharon R.; Tognazzo, Silvia; Agata, Simona; Vaszko, Tibor; Weaver, Joellen; Stavropoulou, Alexandra V.; Buys, Saundra S.; Romero, Atocha; De la Hoya, Miguel; Aittomaki, Kristiina; Muranen, Taru A.; Duran, Mercedes; Chung, Wendy K.; Lasa, Adriana; Miron, Alexander; Benitez, Javier; Senter, Leigha; Huo, Dezheng; Chan, Salina B.; Sokolenko, Anna P.; Chiquette, Jocelyne; Tihomirova, Laima; Friebel, Tara M.; Agnarsson, Bjarni A.; Lu, Karen H.; Lejbkowicz, Flavio; James, Paul A.; Hall, Per; Dunning, Alison M.; Tessier, Daniel C.; Cunningham, Julie M.; Slager, Susan L.; Wang, Chen; Hart, Steven; Stevens, Kristen; Simard, Jacques; Pastinen, Tomi; Pankratz, Vernon S.; Offit, Kenneth; Easton, Douglas F.; Georgia, Chenevix-Trench; Antoniou, Antonis C.; GEMO Study Collaborators; SWE-BRCA (Swedish Breast Cancer Study); Ontario Cancer Genetics Network; HEBON (Hereditary Breast and Ovarian Cancer Research Group Netherlands); EMBRACE (Epidemiological Study of Familial Breast Cancer); BCFR (Breast Cancer Family Registry); Murray, Alex; Hunter, Kent W.

Date:2013-03-27

Abstract:

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancerrisk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breastand 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 = 2.761028, HR = 1.14, 95%CI: 1.09–1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.461028,HR = 1.27, 95% CI: 1.17–1.38) and 4q32.3 (rs4691139, P = 3.461028, HR = 1.20, 95% CI: 1.17–1.38). The 4q32.3 locus was notassociated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 261024). These loci may lead to animproved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution ofthe known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1carriers at lowest risk are 28%–50% compared to 81%–100% for the 5% at highest risk. Similarly, based on the knownovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developingovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk mayhave important implications for risk prediction and clinical management for BRCA1 carriers.

Description:

BRCA1 mutation carriers have increased and variable risksof breast and ovarian cancer. To identify modifiers ofbreast and ovarian cancer risk in this population, a multistageGWAS of 14,351 BRCA1 mutation carriers wasperformed. Loci 1q32 and TCF7L2 at 10q25.3 wereassociated with breast cancer risk, and two loci at 4q32.2and 17q21.31 were associated with ovarian cancer risk. The4q32.3 ovarian cancer locus was not associated withovarian cancer risk in the general population or in BRCA2carriers and is the first indication of a BRCA1-specific risklocus for either breast or ovarian cancer. Furthermore,modeling the influence of these modifiers on cumulativerisk of breast and ovarian cancer in BRCA1 mutationcarriers for the first time showed that a wide range ofindividual absolute risks of each cancer can be estimated.These differences suggest that genetic risk modifiers maybe incorporated into the clinical management of BRCA1mutation carriers.

Conceived and designed the experiments: Fergus J Couch, Douglas FEaston, Georgia Chenevix-Trench, Kenneth Offit, Antonis C Antoniou.Performed the experiments: Fergus J Couch, Julie Cunningham, XianshuWang, Curtis Olswold, Matthew Kosel, Adam Lee, Mia M Gaudet,Kenneth Offit, Franc¸ois Bacot, Daniel Vincent, Daniel Tessier. Analyzedthe data: Antonis C Antoniou, Karoline B Kuchenbaecker, LesleyMcGuffog, Daniel Barrowdale, Andrew Lee, Joe Dennis, Ed Dicks,Vernon S Pankratz, Zachary Fredericksen, Curtis Olswold, MatthewKosel. Contributed reagents/materials/analysis tools: Penny Soucy,Kristen Stevens, Jacques Simard, Tomi Pastinen, Sue Healey, Olga MSinilnikova, Andrew Lee. Wrote the manuscript: Fergus J Couch, DouglasF Easton, Antonis C Antoniou. Collected data and samples and providedcritical review of the manuscript: Fergus J Couch, Xianshu Wang, LesleyMcGuffog, Curtis Olswold, Karoline B Kuchenbaecker, Penny Soucy,Zachary Fredericksen, Daniel Barrowdale, Joe Dennis, Mia M Gaudet, EdDicks, Matthew Kosel, Olga M Sinilnikova, Franc¸ois Bacot, DanielVincent, Frans BL Hogervorst, Susan Peock, Dominique Stoppa-Lyonnet,Anna Jakubowska, Paolo Radice, Rita Katharina Schmutzler, Susan MDomchek, Marion Piedmonte, Christian F Singer, Thomas v O Hansen,Susan L Neuhausen, Csilla I Szabo, Ignacio Blanco, Mark H Greene, BethY Karlan, CatherineM Phelan, Jeffrey NWeitzel, Marco Montagna, EdithOlah, Irene L Andrulis, Andrew K Godwin, Drakoulis Yannoukakos,David E Goldgar, Trinidad Caldes, Heli Nevanlinna, Ana Osorio, MaryBeth Terry, Mary B Daly, Elizabeth J van Rensburg, Ute Hamann, SusanJ Ramus, Amanda Ewart Toland, Maria A Caligo, Olufunmilayo IOlopade, Nadine Tung, Kathleen Claes, Mary S Beattie, Melissa CSouthey, Evgeny N Imyanitov, Ramunas Janavicius, Esther M John, AvaKwong, Orland Diez, Rosa B Barkardottir, Banu K Arun, Gad Rennert,Soo-Hwang Teo, Patricia A Ganz, Annemarie H van der Hout, CarolienHM van Deurzen, Encarna B Go´mez Garcia, Flora E van Leeuwen,Hanne EJ Meijers-Heijboer, Johannes JP Gille, Margreet GEM Ausems,Marinus J Blok, Marjolijn JL Ligtenberg, Matti A Rookus, Peter Devilee,Theo AM van Os, Juul T Wijnen, Debra Frost, Radka Platte, D GarethEvans, Louise Izatt, Rosalind A Eeles, Julian Adlard, Diana M Eccles,Carole Brewer, Patrick J Morrison, Lucy E Side, Alan Donaldson, Mark TRogers, Jacqueline Eason, Helen Gregory, Emma McCann, AlainCalender, Agne`s Hardouin, Pascaline Berthet, Capucine Delnatte,Catherine Nogues, Dominique Leroux, Etienne Rouleau, Fabienne Prieur,Hagay Sobol, Laurence Venat-Bouvet, Laurent Castera, Marion Gauthier-Villars, Me´lanie Le´one´, Yves-Jean Bignon, Elz_bieta Złowocka-Perłowska,Katarzyna Durda, Katarzyna Jaworska, Tomasz Huzarski, AlessandraViel, Bernard Peissel, Bernardo Bonanni, Giulia Melloni, Laura Ottini,Laura Papi, Liliana Varesco, Maria Grazia Tibiletti, Valeria Pensotti,Norbert Arnold, Christoph Engel, Dorothea Gadzicki, Andrea Gehrig,Karin Kast, Kerstin Rhiem, Dieter Niederacher, Nina Ditsch, HansjoergPlendl, Sabine Preisler-Adams, Raymonda Varon-Mateeva, BarbaraWappenschmidt, Bernhard H F Weber, Brita Arver, Marie Stenmark-Askmalm, Richard Rosenquist, Zakaria Einbeigi, Katherine L Nathanson,Timothy R Rebbeck, Stephanie V Blank, David E Cohn, Gustavo CRodriguez, Michael Friedlander, Victoria L Bae-Jump, Anneliese Fink-Retter, Christine Rappaport, Daphne Gschwantler Kaulich, Georg Pfeiler,Muy-Kheng Tea, Bella Kaufman, Shani Shimon Paluch, Yael Laitman,Anne-Marie Gerdes, Inge Sokilde Pedersen, Sanne Traasdahl Moeller,Torben A Kruse, Uffe Birk Jensen, Joseph Vijai, Mark Robson, NoahKauff, Anna Marie Mulligan, Gord Glendon, Hilmi Ozcelik, BentEjlertsen, Finn C Nielsen, Lars Jønson, Mette K Andersen, Yuan ChunDing, Lenka Foretova, Alex Teule´, Miquel Angel Pujana, Phuong L Mai,Jennifer T Loud, Sandra Orsulic, Steven A Narod, Josef Herzog, Sharon RSand, Silvia Tognazzo, Simona Agata, Tibor Vaszko, Joellen Weaver,Alexandra V Stavropoulou, Saundra S Buys, Atocha Romero, Miguel de laHoya, Kristiina Aittoma¨ ki, Taru A Muranen, Mercedes Duran, Wendy KChung, Cecilia M Dorfling, Dezheng Huo, Salina B Chan, Anna PSokolenko, Laima Tihomirova, Tara M Friebel, Bjarni A Agnarsson,Karen H Lu, Flavio Lejbkowicz, Paul A James, Per Hall, Alison MDunning, Daniel Tessier, Susan L Slager, Jacques Simard, Tomi Pastinen, Vernon S Pankratz, Kenneth Offit, Douglas F Easton, Georgia Chenevix-Trench, Antonis C Antoniou, Andrew Lee, Adam Lee, Adriana Lasa,Alexander Miron, Caroline Seynaeve, Christian Sutter, Eitan Friedman,Elena Fineberg, Christine Lasset, Amanda B Spurdle, Anne-Bine Skytte,Alfons Meindl, Claude Houdayer, Fiona Douglas Francesca Damiola,Catherine Houghton, Alex Murray, Jan Lubinski, Conxi Lazaro, ChristineWalsh, Chen Wang, Jenny Lester, Huw Dorkins, Helmut Deissler, IanCampbell, Isabelle Coupier, Judith Balman˜a, Joan Brunet, Javier Benitez,Jackie Cook, Jocelyne Chiquette, Judy Garber, Jacek Gronwald, KaraSarrel, Kristen Stevens, Laurie Small, Leigha Senter, Linda Steele, MadsThomassen, Marc Tischkowitz, Niklas Loman, Noralane M Lindor, PascalPujol, Paolo Peterlongo, Steve Ellis, Stefanie Engert, Sue Healey, ShirleyHodgson, Steven Hart, Sylvie Mazoyer, Siranoush, Manoukian, SennoVerhoef, Sara Volorio.

Show full item record

Files in this item

Name:Couch_Genomewide( ...

Size:2.878Mb

Format:PDF

Description:Article

View/Open

This item appears in the following Collection(s)

  • Research Articles (Genetics)1040
  • Research Articles (University of Pretoria)34821

Showing items related by title, author, creator and subject.

  • Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus 

    Lawrenson, Kate; Kar, Siddhartha; McCue, Karen; Kuchenbaeker, Karoline; Michailidou, Kyriaki; Tyrer, Jonathan; Beesley, Jonathan; Ramus, Susan J.; Li, Qiyuan; Delgado, Melissa K.; Lee, Janet M.; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Bandera, Elisa V.; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Matthias W.; Benitez, Javier; Berchuck, Andrew; Bisogna, Maria; Bjorge, Line; Blomqvist, Carl; Blot, William; Bogdanova, Natalia; Bojesen, Anders; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Borresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Bruinsma, Fiona; Brunet, Joan; Buhari, Shaik Ahmad; Burwinkel, Barbara; Butzow, Ralf; Buys, Saundra S.; Cai, Qiuyin; Caldes, Trinidad; Canniotto, Rikki; Chang-Claude, Jenny; Chiquette, Jocelyne; Choi, Ji-Yeob; Claes, Kathleen B.M.; GEMO Study Collaborators; Campbell, Ian; Cook, Linda S.; Cox, Angela; Cramer, Daniel W.; Cross, Simon S.; Cybulski, Cezary; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Dansonka-Mieszkowskaÿÿ, Agnieszka; Darabi, Hatef; Dennis, Joe; Devilee, Peter; Diez, Orland; Doherty, Jennifer A.; Domchek, Susan M.; Dorfling, Cecilia Maria; Dork, Thilo; Dumont, Martine; Ehrencrona, Hans; Ejlertsen, Bent; Ellis, Steve; EMBRACE; Engel, Christoph; Lee, Eunjung; Evans, D. Gareth; Fasching, Peter A.; Feliubadalo, Lidia; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Flyger, Henrik; Foretova, Lenka; Fostira, Florentia; Foulkes, William D.; Fridley, Brooke L.; Friedman, Eitan; Frost, Debra; Gambino, Gaetana; Garber, Judy; Garcıa-Closas, Montserrat; Gentry-Maharaj, Aleksandra; Ghoussaini, Maya; Giles, Graham G.; Glasspool, Rosalind; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; Gonzalez-Neira, Anna; Goode, Ellen L.; Goodman, Marc T.; Greene, Mark H.; Gronwald, Jacek; Guenel, Pascal; Haiman, Christopher A.; Hall, Per; Hallberg, Emily; Hamann, Ute; Hansen, Thomas V.O.; Harrington, Patricia A.; Hartman, Mikael; Hassan, Norhashimah; Healey, Sue; The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON); Heitz, Florian; Herzog, Josef; Hogdall, Estrid; Hogdall, Claus K.; Hogervorst, Frans B.L.; Hollestelle, Antoinette; Hopper, John L.; Hulick, Peter J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; KConFab Investigators; Australian Ovarian Cancer Study Group; Isaacs, Claudine; Ito, Hidemi; Jakubowska, Anna; Janavicius, Ramunas; Jensen, Allan; John, Esther M.; Johnson, Nichola; Kabisch, Maria; Kang, Daehee; Kapuscinski, Miroslav; Karlan, Beth Y.; Khan, Sofia; Kiemeney, Lambertus A.; Kjaer, Susanne Kruger; Knight, Julia A.; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kupryjanczyk, Jolanta; Kwong, Ava; De la Hoya, Miguel; Laitman, Yael; Lambrechts, Diether; Le, Nhu; De Leeneer, Kim; Lester, Jenny; Levine, Douglas A.; Li, Jingmei; Lindblom, Annika; Long, Jirong; Lophatananon, Artitaya; Loud, Jennifer T.; Lu, Karen; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Le Marchand, Loic; Margolin, Sara; Marme, Frederik; Massuger, Leon F.A.G.; Matsuo, Keitaro; Mazoyer, Sylvie; McGuffog, Lesley; McLean, Catriona; McNeish, Iain; Meindl, Alfons; Menon, Usha; Mensenkamp, Arjen R.; Milne, Roger L.; Montagna, Marco; Moysich, Kirsten B.; Muir, Kenneth; Mulligan, Anna Marie; Nathanson, Katherine L.; Ness, Roberta B.; Neuhausen, Susan L.; Nevanlinna, Heli; Nord, Silje; Nussbaum, Robert L.; Odunsi, Kunle; Offit, Kenneth; Olopade, Olufunmilayo I.; Olson, Janet E.; Olswold, Curtis; O’Malley, David; Orlow, Irene; Orr, Nick; Osorio, Ana; Park, Sue Kyung; Pearce, Celeste L.; Pejovic, Tanja; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M.; Poole, Elizabeth M.; Pylkas, Katri; Radice, Paolo; Rantala, Johanna; Rashid, Muhammad Usman; Rennert, Gad; Rhenius, Valerie; Rhiem, Kerstin; Risch, Harvey A.; Rodriguez, Guz; Rossing, Mary Anne; Rudolph, Anja; Salvesen, Helga B.; Sangrajrang, Suleep*rn; Sawyer, Elinor J.; Schildkraut, Joellen M.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Sellers, Thomas A.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Sieh, Weiva; Singer, Christian F.; Sinilnikova, Olga M.; Slager, Susan; Song, Honglin; Soucy, Penny; Southey, Melissa C.; Stenmark-Askmalm, Marie; Stoppa-Lyonnet, Dominique; Teo, Soo H.; Terry, Kathryn L.; Terry, Mary Beth; Thomassen, Mads; Tibiletti, Maria Grazia; Tihomirova, Laima; Tognazzo, Silvia; Toland, Amanda Ewart; Tomlinson, Ian; Torres, Diana; Truong, Therese; Tseng, Chiu-chen; Tung, Nadine; Tworoger, Shelley S.; Vachon, Celine; Van den Ouweland, Ans M.W.; Van Doorn, Helena C.; Jansen van Rensburg, Elizabeth; Van’t Veer, Laura J.; Vanderstichele, Adriaan; Vergote, Ignace; Vijai, Joseph; Wang, Qin; Wang-Gohrke, Shan; Weitzel, Jeffrey N.; Wentzensen, Nicolas; Whittemore, Alice S.; Wildiers, Hans; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Yoon, Sook-Yee; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Khanna, Kum Kum; Simard, Jacques; Monteiro, Alvaro N.; French, Juliet D.; Couch, Fergus J.; Freedman, Matthew L.; Easton, Douglas F.; Dunning, Alison M.; Pharoah, Paul D.; Edwards, Stacey L.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Gayther, Simon A. (Nature Publishing Group, 2016-09-07)

    A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here weanalyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutationcarriers and 73,444 controls and identify ...

  • Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer 

    Couch, Fergus J.; Kuchenbaecker, Karoline B.; Michailidou, Kyriaki; Mendoza-Fandino, Gustavo A.; Nord, Silje; Lilyquist, Janna; Olswold, Curtis; Hallberg, Emily; Agata, Simona; Ahsan, Habibul; Aittomaki, Kristiina; Ambrosone, Christine; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Arun, Banu K.; Arver, Brita; Barile, Monica; Barkardottir, Rosa B.; Barrowdale, Daniel; Beckmann, Lars; Beckmann, Matthias W.; Benitez, Javier; Blank, Stephanie V.; Blomqvist, Carl; Bogdanova, Natalia V.; Bojesen, Stig E.; Bolla, Manjeet K.; Bonanni, Bernardo; Brauch, Hiltrud; Brenner, Hermann; Burwinkel, Barbara; Buys, Saundra S.; Caldes, Trinidad; Caligo, Maria A.; Canzian, Federico; Carpenter, Jane; Chang-Claude, Jenny; Chanock, Stephen J.; Chunk, Wendy K.; Claes, Kathleen B. M.; Cox, Angela; Cross, Simon S.; Cunningham, Julie M.; Czene, Kamila; Daly, Mary B.; Damiola, Francesca; Darabi, Hatef; De la Hoya, Miguel; Devilee, Peter; Diez, Orland; Ding, Yuan C.; Dolcetti, Riccardo; Domchek, Susan M.; Dorfling, Cecilia Maria; Dos-Santos-Silva, Isabel; Dumont, Martine; Dunning, Alison M.; Eccles, Diana M.; Ehrencrona, Hans; Ekici, Arif B.; Eliassen, Heather; Ellis, Steve; Fasching, Peter A.; Figueroa, Jonine; Flesch-Janys, Dieter; Forsti, Asta; Fostira, Florentia; Foulkes, William D.; Friebel, Tara; Friedman, Eitan; Frost, Debra; Gabrielson, Marike; Gammon, Marilie D.; Ganz, Patricia A.; Gapstur, Susan M.; Garber, Judy; Gaudet, Mia M.; Gayther, Simon A.; Gerdes, Anne-Marie; Ghoussaini, Maya; Giles, Graham G.; Glendon, Gord; Godwin, Andrew K.; Goldberg, Mark S.; Goldgar, David E.; Gonzalez-Neira, Anna; Greene, Mark H.; Gronwald, Jacek; Guenel, Pascal; Gunter, Marc; Haeberle, Lothar; Haiman, Christopher A.; Hamann, Ute; Hansen, Thomas V.O.; Hart, Steven; Healey, Sue; Heikkinen, Tuomas; Henderson, Brian E.; Herzog, Josef; Hogervorst, Frans B.L.; Hollestelle, Antoinette; Hooning, Maartje J.; Hoover, Robert N.; Hopper, John L.; Hunter, David J.; Huzarski, Tomasz; Imyanitov, Evgeny N.; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Janavicius, Ramunas; Jensen, Uffe Birk; John, Esther M.; Jones, Michael; Kabisch, Maria; Kar, Siddhartha; Karlan, Beth Y.; Khan, Sofia; Khaw, Kay-Tee; Kibriya, Muhammad G.; Knight, Julia A.; Ko, Yon-Dschun; Konstantopoulou, Irene; Kosma, Veli-Matti; Kristensen, Vessela; Kwong, Ava; Laitman, Yael; Lambrechts, Diether; Lazaro, Conxi; Lee, Eunjung; Le Marchand, Loic; Lester, Jenny; Lindblom, Annika; Lindor, Noralane; Lindstrom, Sara; Liu, Jianjun; Long, Jirong; Lubinski, Jan; Mai, Phuong L.; Makalic, Enes; Malone, Kathleen E.; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Frederik; Martens, John W. M.; McGuffog, Lesley; Meindl, Alfons; Miller, Austin; Milne, Roger L.; Miron, Penelope; Montagna, Marco; Mazoyer, Sylvie; Mulligan, Anna M.; Muranen, Taru A.; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Nordestgaard, Borge G.; Nussbaum, Robert L.; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I.; Olson, Janet E.; Osorio, Ana; Park, Sue K.; Peeters, Petra H.; Peissel, Bernard; Peterlongo, Paolo; Julian, Peto; Phelan, Catherine M.; Pilarski, Robert; Poppe, Bruce; Pylkas, Katri; Radice, Paolo; Rahman, Nazneen; Johanna, Rantala; Rappaport, Christine; Rennert, Gad; Richardson, Andrea; Robson, Mark; Romieu, Isabelle; Rudolph, Anja; Rutgers, Emiel J.; Sanchez, Maria-Jose; Santella, Regina M.; Sawyer, Elinor J.; Schmidt, Daniel F.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Schumacher, Fredrick; Scott, Rodney; Senter, Leigha; Sharma, Priyanka; Simard, Jacques; Singer, Christian F.; Sinilnikova, Olga M.; Soucy, Penny; Southey, Melissa; Steinemann-Askmalm, Doris; Stoppa-Lyonnet, Dominique; Swerdlow, Anthony; Szabo, Csilla I.; Tamimi, Rulla; Tapper, William; Teixeira, Manuel R.; Teo, Soo-Hwang; Terry, Mary B.; Thomassen, Mads; Thompson, Deborah; Tihomirova, Laima; Toland, Amanda Ewart; Tollenaar, Robert A.E.M.; Tomlinson, Ian; Truong, Therese; Tsimiklis, Helen; Teule, Alex; Tumino, Rosario; Tung, Nadine; Turnbull, Clare; Ursin, Giski; Van Deurzen, Carolien H.M.; Jansen van Rensburg, Elizabeth; Varon-Mateeva, Raymonda; Wang, Zhaoming; Wang-Gohrke, Shan; Weiderpass, Elisabete; Weitzel, Jeffrey N.; Whittemore, Alice; Wildiers, Hans; Winqvist, Robert; Yang, Xiaohong R.; Yannoukakos, Drakoulis; Yao, Song; Zamora, M. Pilar; Zheng, Wei; Hall, Per; Kraft, Peter; Vachon, Celine; Slager, Susan; Chenevix-Trench, Georgia; Pharoah, Paul D.P.; Monteiro, Alvaro A.N.; Garcıa-Closas, Montserrat; Easton, Douglas F.; Antoniou, Antonis C. (Nature Publishing Group, 2016-04-27)

    Common variants in 94 loci have been associated with breast cancer including 15 loci withgenome-wide significant associations (Po5 10 8) with oestrogen receptor (ER)-negativebreast cancer and BRCA1-associated breast ...

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

    Barnes, Daniel R.; Rookus, Matti A.; McGuffog, Lesley; Leslie, Goska; Mooij, Thea M.; Dennis, Joe; Mavaddat, Nasim; Adlard, Julian; Ahmed, Munaza; Aittomäki, Kristiina; Andrieu, Nadine; Andrulis, Irene L.; Arnold, Norbert; Arun, Banu K.; Azzollini, Jacopo; Balmana, Judith; Barkardottir, Rosa B.; Barrowdale, Daniel; Benitez, Javier; Berthet, Pascaline; Białkowska, Katarzyna; Blanco, Amie M.; Blok, Marinus J.; Bonanni, Bernardo; Boonen, Susanne E.; Borg, Ake; Bozsik, Aniko; Bradbury, Angela R.; Brennan, Paul; Brewer, Carole; Brunet, Joan; Buys, Saundra S.; Caldes, Trinidad; Caligo, Maria A.; Campbell, Ian; Christensen, Lise Lotte; Chung, Wendy K.; Claes, Kathleen B.M.; Colas, Chrystelle; Collonge-Rame, Marie-Agnes; Cook, Jackie; Daly, Mary B.; Davidson, Rosemarie; De la Hoya, Miguel; De Putter, Robin; Delnatte, Capucine; Devilee, Peter; Diez, Orland; Ding, Yuan Chun; Domchek, Susan M.; Dorfling, Cecilia Maria; Ejlertsen, Bent; Engel, Christoph; Evans, D. Gareth; Faivre, Laurence; Foretova, Lenka; Fostira, Florentia; Friedlander, Michael; Friedman, Eitan; Frost, Debra; Ganz, Patricia A.; Garber, Judy; Gehrig, Andrea; Gerdes, Anne-Marie; Gesta, Paul; Giraud, Sophie; Glendon, Gord; Godwin, Andrew K.; Goldgar, David E.; González-Neira, Anna; Greene, Mark H.; Gschwantler-Kaulich, Daphne; Hahnen, Eric; Hamann, Ute; Hanson, Helen; Hentschel, Julia; Hogervorst, Frans B.L.; Hooning, Maartje J.; Horvath, Judit; Hu, Chunling; Hulick, Peter J.; Imyanitov, Evgeny N.; Isaacs, Claudine; Izatt, Louise; Izquierdo, Angel; Jakubowska, Anna; James, Paul A.; Janavicius, Ramunas; John, Esther M.; Joseph, Vijai; Karlan, Beth Y.; Kast, Karin; Koudijs, Marco; Kruse, Torben A.; Kwong, Ava; Laitman, Yael; Lasset, Christine; Lazaro, Conxi; Lester, Jenny; Lesueur, Fabienne; Liljegren, Annelie; Loud, Jennifer T.; Lubinski, Jan; Mai, Phuong L.; Manoukian, Siranoush; Mari, Veronique; Mebirouk, Noura; Meijers-Heijboer, Hanne E.J.; Meindl, Alfons; Mensenkamp, Arjen R.; Miller, Austin; Montagna, Marco; Mouret-Fourme, Emmanuelle; Mukherjee, Semanti; Mulligan, Anna Marie; Nathanson, Katherine L.; Neuhausen, Susan L.; Nevanlinna, Heli; Niederacher, Dieter; Nielsen, Finn Cilius; Nikitina-Zake, Liene; Nogues, Catherine; Olah, Edith; Olopade, Olufunmilayo I.; Ong, Kai-ren; O’Shaughnessy-Kirwan, Aoife; Osorio, Ana; Ott, Claus-Eric; Papi, Laura; Park, Sue K.; Parsons, Michael T.; Pedersen, Inge Sokilde; Peissel, Bernard; Peixoto, Ana; Peterlongo, Paolo; Pfeiler, Georg; Phillips, Kelly-Anne; Prajzendanc, Karolina; Pujana, Miquel Angel; Radice, Paolo; Ramser, Juliane; Ramus, Susan J.; Rantala, Johanna; Rennert, Gad; Risch, Harvey A.; Robson, Mark; Ronlund, Karina; Salani, Ritu; Schuster, Helene; Senter, Leigha; Shah, Payal D.; Sharma, Priyanka; Side, Lucy E.; Singer, Christian F.; Slavin, Thomas P.; Soucy, Penny; Southey, Melissa C.; Spurdle, Amanda B.; Steinemann, Doris; Steinsnyder, Zoe; Stoppa-Lyonnet, Dominique; Sutter, Christian; Tan, Yen Yen; Teixeira, Manuel R.; Teo, Soo Hwang; Thull, Darcy L.; Tischkowitz, Marc; Tognazzo, Silvia; Toland, Amanda E.; Trainer, Alison H.; Tung, Nadine; Van Engelen, Klaartje; Jansen van Rensburg, Elizabeth; Vega, Ana; Vierstraete, Jeroen; Wagner, Gabriel; Walker, Lisa; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weitzel, Jeffrey N.; Yadav, Siddhartha; Yang, Xin; Yannoukakos, Drakoulis; Zimbalatti, Dario; Offit, Kenneth; Thomassen, Mads; Couch, Fergus J.; Schmutzler, Rita K.; Simard, Jacques; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C. (Nature Publishing Group, 2020-10)

    PURPOSE : We assessed the associations between population-basedpolygenic risk scores (PRS) for breast (BC) or epithelial ovariancancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenicvariant carriers.METHODS ...

Genome-wide association study in BRCA1 mutation carriers identifies Novel Loci associated with breast and ovarian cancer risk (2024)

FAQs

Are the BRCA1 and BRCA2 genes associated with an increased risk of ovarian cancer? ›

The estimated risk of ovarian cancer in women with a BRCA1 mutation is 39 to 46 percent by age 70. For women with a BRCA2 mutation, the risk of ovarian cancer by age 70 is 10 to 27 percent. Do BRCA mutations increase the risk of other types of cancer? Yes.

What is the gene locus for BRCA1? ›

The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair 41,196,312 to base pair 41,277,500 (Build GRCh37/hg19) (map). BRCA1 orthologs have been identified in most vertebrates for which complete genome data are available.

What is the BRCA1 mutation in ovarian cancer cell lines? ›

Deleterious BRCA1 mutations were identified in 4 ovarian cell lines IGROV-1, UPN-251, HI0180 and SNU-251 (Tables 2 and 3). The deletion of an adenine at position 2080 in the IGROV-1 cell line, leads to a premature stop of protein trans- lation at amino acid 700.

What are the chances of getting breast cancer with the BRCA1 mutation? ›

It is high. Having a BRCA mutation means you have a likelihood of 45% to 85% for developing breast cancer in your lifetime, along with a 10% to 46% chance of ovarian cancer. The probability of breast cancer among the general population is about 12%.

What is the life expectancy of someone with BRCA1? ›

About 12 percent of the women had a mutation in either BRCA1 or BRCA2 that raised cancer risk. A person's cancer risk can vary a lot depending on which mutation they have. Most of the women lived 10 years; 73 percent of the women with BRCA mutations lived 10 years and 70 percent of women without the mutations did.

What percentage of ovarian cancer patients have a BRCA mutation? ›

Approximately 15% of patients with ovarian cancer have a germline BRCA (gBRCA) variation,1 which has important implications, including increased sensitivity to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors and improved survival.

What happens if you test positive for BRCA1? ›

A positive test result indicates that a person has inherited a known harmful variant in BRCA1 or BRCA2 (these are typically called “pathogenic” or “likely pathogenic” variants on laboratory test reports) and has an increased risk of developing certain cancers.

What does it mean if you have the BRCA1 gene? ›

Mutations in the BRCA1 gene are associated with an increased risk of breast cancer in both men and women, as well as several other types of cancer. These mutations are present in every cell in the body and can be passed from one generation to the next.

Should you get a mastectomy if you have the BRCA gene? ›

Most women with a BRCA1 or BRCA2 gene mutation will develop breast cancer at some point. Having a prophylactic mastectomy before the cancer develops might add many years to their lives. But not all women with BRCA1 or BRCA2 mutations develop breast cancer. For some women the surgery might not have been helpful.

Is BRCA1 a tumor marker? ›

The BRCA gene test looks for DNA changes that increase the risk of breast cancer and ovarian cancer. BRCA1 and BRCA2 are the most well-known genes. Testing often looks for those genes and many other genes that increase the risk of breast and ovarian cancers.

What cancers are associated with the BRCA1 mutation? ›

BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for male and female breast cancer, ovarian cancer (including fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate, pancreatic, and melanoma, primarily in ...

What gene is faulty in ovarian cancer? ›

Between 5 and 15 out of 100 ovarian cancers (5 to 15%) are caused by an inherited faulty gene. Inherited genes that increase the risk of ovarian cancer include faulty versions of BRCA1 and BRCA2. Faults in these genes also increase the risk of breast cancer.

Is breast cancer inherited from mother or father? ›

Hereditary breast and ovarian cancer

About 5% to 10% of breast and 10% to 15% of ovarian cancers are hereditary. Hereditary cancer means cancer runs in your family. It could be caused by a change in certain genes that you inherited from your mother or father.

Can you still get breast cancer without the BRCA gene? ›

Genetic testing gives people the chance to learn if their breast cancer or family history of breast cancer is due to an inherited gene mutation. Most women who get breast cancer don't have a BRCA1 or BRCA2 (BRCA1/2) or other high-risk inherited gene mutation related to breast cancer.

What is the major cause of breast cancer almost everyone ignores? ›

These include hormones, lifestyle choices and things in the environment. But it's not clear why some people who don't have any factors get cancer, yet others with risk factors never do. It's likely that breast cancer happens through a complex interaction of your genetic makeup and the world around you.

Which genes are associated with an increased risk of ovarian cancer? ›

Variants in the RAD51C, RAD51D and BRIP1 genes can increase the risk of developing ovarian cancer.

What do the genes BRCA1 and BRCA2 increase the risk of? ›

BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for male and female breast cancer, ovarian cancer (including fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate, pancreatic, and melanoma, primarily in ...

Who is at high risk for ovarian cancer? ›

Reproductive history – Women who began menstruating before age 12, have never been pregnant, have unexplained infertility, have never taken oral contraceptives, had their first child after age 30 or experienced menopause after age 55 have an increased risk of ovarian cancer.

Which is worse, BRCA1 or BRCA2? ›

Which Gene Mutation is Worse, BRCA1 or BRCA2? By age 70, women BRCA1 carriers have a slightly higher risk of developing breast cancer than BRCA2 carriers. Also, BRCA1 mutations are more often linked to triple negative breast cancer, which is more aggressive and harder to treat than other types of breast cancer.

References

Top Articles
Latest Posts
Article information

Author: Eusebia Nader

Last Updated:

Views: 6097

Rating: 5 / 5 (60 voted)

Reviews: 83% of readers found this page helpful

Author information

Name: Eusebia Nader

Birthday: 1994-11-11

Address: Apt. 721 977 Ebert Meadows, Jereville, GA 73618-6603

Phone: +2316203969400

Job: International Farming Consultant

Hobby: Reading, Photography, Shooting, Singing, Magic, Kayaking, Mushroom hunting

Introduction: My name is Eusebia Nader, I am a encouraging, brainy, lively, nice, famous, healthy, clever person who loves writing and wants to share my knowledge and understanding with you.