Citations 5
PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS
Southey, Melissa C. , Goldgar, David E, Winqvist, Robert , Pylkäs, Katri , Michailidou, Kyriaki , Rensburg, Elizabeth J. van , Heikkinen, Tuomas , Hopper, John L. , Dörk, Thilo , Claes, Kathleen , Teo, Zhi L. , Radice, Paolo , Catucci, Irene, Peterlongo, Paolo , Odefrey, Fabrice, Dowty, James G., Schmidt, Marjanka K. , Hogervorst, Frans B.L., Verhoef, Senno, Carpenter, Jane, Clarke, Christine L. , Scott, Rodney J. , Fasching, Peter A. , Haeberle, Lothar, Ekici, Arif B. , Beckmann, Matthias W. , Peto, Julian , Fletcher, Olivia , Johnson, Nichola , Bolla, Manjeet K. , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Miller, Nicola, Marmé, F., Burwinkel, Barbara , Guénel, Pascal , Truong, Thérèse , Sanchez, Marie, Bojesen, Stig E. , Nielsen, Sune F. , Flyger, Henrik, Benı́tez, Javier , Zamora, M. Pilar , Menéndez, Primitiva, Brenner, Hermann , Stegmaier, Christa, Brauch, Hiltrud , Brüning, Thomas , Ko, Yon‐Dschun, Muranen, Taru , Aittomäki, Kristiina, Blomqvist, Carl , Bogdanova, Natalia , Antonenkova, Natalia, Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kataja, Vesa , Kosma, Veli‐Matti , Hartikainen, Jaana M. , Investigators, kConFab, Group, Australian Ovarian Cancer Study, Wauters, Els , Smeets, Dominiek, Beuselinck, Benoit , Floris, Giuseppe , Chang‐Claude, Jenny , Flesch‐Janys, Dieter, Vachon, Celine M. , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Schumacher, Fredrick R. , Kristensen, Vessela, Alnæs, Grethe Grenaker, Zheng, Wei , Hunter, David J. , Lindström, Sara, Hankinson, Susan E. , Kraft, Peter , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Jukkola‐Vuorinen, Arja , Grip, Mervi, Kauppila, Saila , Devilee, Peter , Tollenaar, Robert A.E.M., Seynaeve, Caroline, García‐Closas, Montserrat , Figueroa, Jonine D. , Lissowska, Jolanta , Darabi, Hatef, Eriksson, Mikael , Eccles, Diana M, Tapper, William , Gerty, Sue, Hooning, Maartje J. , Collée, J. 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Ann , Chen, Zhihua , Gayther, Simon A. , Ramus, Susan J. , Menon, Usha , Wu, Anna H. , Pearce, Celeste Leigh, Pike, Malcolm C., Dansonka‐Mieszkowska, Agnieszka , Plisiecka-Hałasa, Joanna, Moes-Sosnowska, Joanna , Kupryjańczyk, Jolanta , Song, Honglin , Winship, Ingrid , Chenevix‐Trench, Georgia , Tavtigian, Sean V. , Easton, Doug , Lu, Karen H. , Durocher, Francine , Eccles, Diana , Lambrechts, Diether , Vachon, Celine, Pankratz, Vernon S, Thibodeau, Stephen, Goldgar, David E, Couch, Fergus J. , Tischkowitz, Marc D. , Foulkes, William D. , Dennis, Joe , Nevanlinna, Heli , Reis‐Filho, Jorge S. , Tsimiklis, Helen , Broeks, Annegien , dos‐Santos‐Silva, Isabel , Yang, Rongxi , Ménégaux, F. , Sanchez, Marie, Pérez, José Ignacio Arias , Anton‐Culver, Hoda , Neuhausen, Susan L. , Ziogas, Argyrios , Clarke, Christina A. , Arndt, Volker , Mannermaa, Arto, Spurdle, Amanda B. , Group, Australian Ovarian Cancer Study, Rudolph, Anja , Seibold, Petra , Olson, Janet E. , Vachon, Celine M. , Pankratz, V. Shane , Marchand, Loı̈c Le , Kristensen, Vessela N. , Hankinson, Susan E. , Hollestelle, Antoinette , Chanock, Stephen Jacob , Czene, Kamila , Eriksson, Mikael , Eccles, Diana M, Rafiq, Sajjad , Hooning, Maartje J. , Martens, John W.M. , Hall, Per N , Cox, Angela , Toland, Amanda Ewart , Ambrosone, Christine B. , Wiklund, Fredrik E. , Khaw, Kay‐Tee , Cybulski, Cezary , Cannon‐Albright, Lisa , Park, Jong, Kote‐Jarai, Zsofia , Renner, Stefan P. , Doherty, Jennifer A. , Wilkens, Lynne R. , Bützow, Ralf C. , Modugno, Francesmary , Moysich, Kirsten B., Bois, Andreas du , Karlan, Beth Y. , Kjær, Susanne K. , Bonanni, Bernardo , Fridley, Brooke L. , Larson, Melissa C. , Hildebrandt, Michelle A.T. , Dao, Fanny , Berchuck, Andrew , Cramer, Daniel W. , Poole, Elizabeth M. , Bandera, Elisa V. , Orlow, Irene , Bjørge, Line , Pejovic, Tanja B. , Brooks‐Wilson, Angela , Cook, Linda S. , Gronwald, Jacek , Tyrer, Jonathan P. , Paul, James , Siddiqui, Nadeem , Glasspool, Rosalind , Shu, Xiao‐Ou , McLaughlin, John R, Permuth, Jennifer B. , Gentry‐Maharaj, Aleksandra , Berg, David Van Den , Pharoah, Paul D.P. , Giles, Graham G. , Milne, Roger L. , Pelttari, L M , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Tworoger, Shelley S , van Rensburg, Elizabeth J , Hein, Alexander , Hillemanns, Peter , Jensen, Allan , Vierkant, Robert A , Eccles, Diana , Menon, Usha , Monteiro, Alvaro N , Swerdlow, Anthony J , Moysich, Kirsten , Radice, Paolo , Lissowska, Jolanta , Claes, Kathleen B M , Campbell, Ian G , Eeles, Rosalind A , Southey, Melissa C , Menkiszak, Janusz , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Lin, Hui-Yi , Fogarty, Zachary C , Dunning, Alison M , Heitz, Florian , Jakubowska, Anna , Jones, Michael E , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Brenner, Hermann , Guénel, Pascal , Li, Jingmei , Muranen, Taru A , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Winship, Ingrid M , Ekici, Arif B , Michailidou, Kyriaki , Hartikainen, Jaana M , Bogdanova, Natalia V , Kraft, Peter , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Høgdall, Estrid , Høgdall, Claus K , Batra, Jyotsna , Pylkäs, Katri , Yannoukakos, Drakoulis , Devilee, Peter , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Goodman, Marc T , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick
Journal of Medical Genetics | September 5, 2016 | Volume: 53 | Issue: 12 | Pages: 800-811
Background The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study. Methods We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant. Results For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants. Conclusions This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
Kar, Siddhartha , Beesley, Jonathan, Olama, Ali Amin Al , Michailidou, Kyriaki , Lawrenson, Kate , Lindström, Sara, Ramus, Susan J. , Thompson, Deborah J. , Investigators, ABCTB, Kibel, Adam S. , Dansonka‐Mieszkowska, Agnieszka , Michael, Agnieszka , Dieffenbach, Aida Karina, Whittemore, Alice S. , Monteiro, Álvaro N.A. , Peixoto, Ana , González‐Neira, Anna , Wu, Anna H. , Lindblom, Annika , Swerdlow, Anthony J. , Cancer), AOCS Study Group & Australian Cancer Study (Ovarian, BioResource, APCB, Ekici, Arif B. , Burwinkel, Barbara , Nordestgaard, Børge G. , Blomqvist, Carl , Phelan, Catherine, McLean, Catriona , Pearce, Celeste Leigh, Vachon, Celine M. , Stegmaier, Christa, Maier, Christiane, Høgdall, Claus , Kang, Daehee , Tessier, Daniel C., Schaid, Daniel J. , Neal, David E. , Eccles, Diana , Flesch‐Janys, Dieter, Wokozorczyk, Dominika, Levine, Douglas A. , Yannoukakos, Drakoulis , Sawyer, Elinor J. , Goode, Ellen L. , Хуснутдинова, Э. К. , Høgdall, Estrid , Song, Fengju, Bruinsma, Fiona, Heitz, Florian , Hamdy, Freddie C. , Olsson, Håkan , Wildiers, Hans , Ulmer, Hans-Ulrich, Pandha, Hardev , Darabi, Hatef, Salvesen, Helga B., Grönberg, Henrik , Brenner, Hermann , Brauch, Hiltrud , Song, Honglin , Lim, Hui-Yi, McNeish, Iain A. , Campbell, Ian , Vergote, Ignace , Lubiński, Jan , Stanford, Janet L. , Benı́tez, Javier , Chang‐Claude, Jenny , Donovan, Jenny , Schildkraut, Joellen M. , Schleutker, Johanna , Hopper, John L. , Kupryjańczyk, Jolanta , Figueroa, Jonine D. , Clements, Judith A. , Knight, Julia A. , Peto, Julian , Cunningham, Julie M. , Pow‐Sang, Julio M. , Batra, Jyotsna , Lu, Karen H., Herkommer, Kathleen , Investigators, kConFab, Matsuo, Keitaro , Muir, Kenneth , Offitt, Kenneth, Chen, Kexin , Moysich, Kirsten B., Aittomäki, Kristiina, Odunsi, Kunle , Kiemeney, Lambertus A. , Massuger, Leon F.A.G. , Hooning, Maartje J. , Pike, Malcolm C., Bolla, Manjeet K. , Luedeke, Manuel, Teixeira, Manuel R. , Goodman, Marc T. , Schmidt, Marjanka K. , Riggan, Marjorie J. , Rossing, Mary Anne, Beckmann, Matthias W. , Moisse, Matthieu , Southey, Melissa C. , Jones, Michael E. , Hildebrandt, Michelle A.T., Hou, Ming‐Feng , Schoemaker, Minouk J. , García‐Closas, Montserrat , Bogdanova, Natalia , Investigators, NBCS, Le, Nhu D. , Orr, Nick , Wentzensen, Nicolas , Pashayan, Nora , Peterlongo, Paolo , Guénel, Pascal , Brennan, Paul , Paulo, Paula , Webb, Penelope M. , Broberg, Per, Fasching, Peter A. , Devilee, Peter , Wang, Qin, Kaneva, Radka , Kopperud, Reidun Kristin, Schmutzler, Rita K., Stephenson, Robert A., MacInnis, Robert J. , Hoover, Robert N. , Winqvist, Robert , Ness, Roberta B., Travis, Ruth C. , Benlloch, Sara, Olson, Sara H. , McDonnell, Shannon K. , Tworoger, Shelley S. , Maia, Sofia , Berndt, Sonja I., Lee, Soo Chin , Teo, Soo‐Hwang , Thibodeau, Stephen N. , Bojesen, Stig E. , Gapstur, Susan M. , Tammela, Teuvo L.J. , Network, the GENICA, Dörk, Thilo , Brüning, Thomas , Wahlfors, Tiina , Edwards, Todd L., Menon, Usha , Hamann, Ute , Mitev, Vanio , Kosma, Veli‐Matti , Setiawan, Veronica Wendy , Kristensen, Vessela, Vogel, Walther , Zheng, Wei , Sieh, Weiva , Blot, William J. , Kluźniak, Wojciech , Gao, Yu‐Tang , Schumacher, Fredrick R. , Freedman, Matthew L., Dunning, Alison M. , Simard, Jacques , Haiman, Christopher A. , Sellers, Thomas A. , Hunter, David J. , Henderson, Brian E., Kraft, Peter , Gayther, Simon A. , Easton, Douglas F. , Chenevix‐Trench, Georgia , Eeles, Rosalind A. , Lambrechts, Diether , Lu, Karen H. , Durocher, Francine , Zheng, Wei , Thorne, Heather , Lambrechts, Diether , Chen, Kexin , Vachon, Celine, Tyrer, Jonathan P. , Kote‐Jarai, Zsofia , Investigators, ABCTB, Gentry‐Maharaj, Aleksandra , Wolk, Alicja , Kierzek, Andrzej , Cox, Angela , Rudolph, Anja , Cancer), AOCS Study Group & Australian Cancer Study (Ovarian, BioResource, APCB, Ziogas, Argyrios , Karlan, Beth Y. , Vachon, Celine M. , Cybulski, Cezary , Slavov, Chavdar , Ambrosone, Christine B. , Teerlink, Craig C. , Stram, Daniel O. , Cramer, Daniel W. , Edwards, Digna R. Velez , Bandera, Elisa V. , Poole, Elizabeth M. , Song, Fengju , Modugno, Francesmary , Wiklund, Fredrik E. , Giles, Graham G. , Risch, Harvey A. , Nevanlinna, Heli , Anton‐Culver, Hoda , Gronwald, Jacek , Doherty, Jennifer A. , Permuth, Jennifer B. , Dennis, Joe , Park, Jong Y. , Czene, Kamila , Khaw, Kay‐Tee , Investigators, kConFab, Moysich, Kirsten B., FitzGerald, Liesel M. , Cook, Linda S. , Cannon‐Albright, Lisa , Hooning, Maartje J. , Aly, Markus , Sanderson, Maureen , Lush, Michael J. , Hildebrandt, Michelle A.T. , Rahman, Nazneen , Investigators, NBCS, Wang, Qin, Cai, Qiuyin , Li, Qiyuan , Bützow, Ralf C. , Milne, Roger L. , Berndt, Sonja I. , Kjær, Susanne K. , Pejovic, Tanja B. , Network, the GENICA, Key, Tim , Kristensen, Vessela N. , Arndt, Volker , Shu, Xiao‐Ou , Berchuck, Andrew , Spurdle, Amanda B. , Chanock, Stephen Jacob , Couch, Fergus J. , Hall, Per N , Pharoah, Paul D.P. , Dörk, Thilo , Lambrechts, Diether , Kiemeney, Lambertus A , McNeish, Iain A , Peterlongo, Paolo , Ramus, Susan J , Teixeira, Manuel R , Teo, Soo H , Tworoger, Shelley S , Webb, Penelope M , Eccles, Diana , Menon, Usha , Lawrenson, Kate , Monteiro, Alvaro N , Swerdlow, Anthony J , Moysich, Kirsten , Campbell, Ian G , Eeles, Rosalind A , Southey, Melissa C , Donovan, Jenny L , Muir, Kenneth , Schleutker, Johanna , Travis, Ruth C , Pashayan, Nora , Michael, Agnieszka , Maclnnis, Robert , Matsuo, Keitaro , Dunning, Alison M , Heitz, Florian , Jones, Michael E , Kupryjanczyk, Jolanta , Lambrechts, Diether , Sieh, Weiva , Brenner, Hermann , Guénel, Pascal , García-Closas, Montserrat , Schmidt, Marjanka K , Ekici, Arif B , Moisse, Matthieu , Michailidou, Kyriaki , Bogdanova, Natalia V , Kraft, Peter , Benitez, Javier , Simard, Jacques , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Høgdall, Estrid , Høgdall, Claus K , Kar, Siddhartha , Batra, Jyotsna , Clements, Judith , Setiawan, Veronica W , Yannoukakos, Drakoulis , Devilee, Peter , Lubinski, Jan , Bojesen, Stig E , Schoemaker, Minouk J , Goodman, Marc T , Wildiers, Hans , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick , McDonnell, Shannon K , Kang, Daehee
Cancer Discovery | July 18, 2016 | Volume: 6 | Issue: 9 | Pages: 1052-1067
Abstract Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type–specific expression quantitative trait locus and enhancer–gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis. Significance: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052–67. ©2016 AACR. This article is highlighted in the In This Issue feature, p. 932
No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing
Easton, Douglas F. , Lesueur, Fabienne , Decker, Brennan , Michailidou, Kyriaki , Li, Jun , Allen, Jamie , Luccarini, Craig , Pooley, Karen A. , Shah, Mitul , Bolla, Manjeet K. , Wang, Qin, Ahmad, Jamil , Thompson, Ella R. , Pertesi, Maroulio , Voegele, Catherine , Mebirouk, Noura, Robinot, Nivonirina , Forey, Nathalie, Luben, Robert , Aittomäki, Kristiina, Group, Australian Ovarian Cancer Study, Baynes, Caroline, Beckman, Matthias W., Benı́tez, Javier , Blot, William J. , Bogdanova, Natalia , Bojesen, Stig E. , Brenner, Hermann , Chang‐Claude, Jenny , Chia, Kee Seng , Choi, Ji‐Yeob , Conroy, Don, Darabi, Hatef, Devilee, Peter , Eriksson, Mikael , Fasching, Peter A. , Figueroa, Jonine D. , Flyger, Henrik, García‐Closas, Montserrat , Giles, Graham G. , Glendon, Gord, Guénel, Pascal , Haiman, Christopher A., Hart, Steven N. , Hartman, Mikael , Hooning, Maartje J. , Hsiung, Chia‐Ni , Jakubowska, Anna , James, Paul A. , John, Esther M. , Johnson, Nichola , Jones, Michael E. , Kabisch, Maria, Kang, Daehee , Investigators, kConFab, Kosma, Veli‐Matti , Kristensen, Vessela, Lambrechts, Diether , Li, Na , Investigators, Lifepool, Lindblom, Annika , Long, Jirong , Lophatananon, Artitaya, Lubiński, Jan , Mannermaa, Arto, Manoukian, Siranoush , Margolin, Sara , Matsuo, Keitaro , Meindl, Alfons , Mitchell, Gillian, Investigators, NBCS, Nevelsteen, Ines, Ouweland, Ans van den, Peterlongo, Paolo , Phuah, Sze Yee, Pylkäs, Katri , Rowley, Simone M. , Sangrajrang, Suleeporn , Schmutzler, Rita K., Shen, Chen‐Yang , Southey, Melissa C. , Surowy, Harald , Swerdlow, Anthony J. , Teo, Soo‐Hwang , Tollenaar, Rob A.�E.�M. , Tomlinson, Ian , Torres, Diana , Truong, Thérèse , Vachon, Celine M. , Verhoef, Senno, Wong‐Brown, Michelle W. , Zheng, Wei , Zheng, Ying , Scott, Rodney J. , Andrulis, Irene L. , Wu, Anna H. , Hopper, John L. , Winqvist, Robert , Burwinkel, Barbara , Sawyer, Elinor J. , Schmidt, Marjanka K. , Dörk, Thilo , Brauch, Hiltrud , Hamann, Ute, Fletcher, Olivia , Campbell, Ian , Dunning, Alison M. , Calvez‐Kelm, Florence Le , Goldgar, David E, Tavtigian, Sean V. , Chenevix‐Trench, Georgia , Thorne, Heather , Lambrechts, Diether , Luben, Robert N , Vachon, Celine, Decker, Brennan , Wang, Qin, Dennis, Joe , Damiola, Francesca , Durand, Geoffroy , Ahmed, Shahana , Anton‐Culver, Hoda , Arndt, Volker , Group, Australian Ovarian Cancer Study, Berg, David Van Den , Cox, Angela , Cross, Simon S. , Czene, Kamila , Eriksson, Mikael , Fostira, Florentia , González‐Neira, Anna , Hall, Per N , Hooning, Maartje J. , Ito, Hidemi , Investigators, kConFab, Kristensen, Vessela N. , Investigators, Lifepool, Mannermaa, Arto, Meindl, Alfons , Muir, Kenneth , Investigators, NBCS, Shu, Xiao‐Ou , Vachon, Celine M. , Nevanlinna, Heli , Couch, Fergus J. , Rudolph, Anja , Neuhausen, Susan L. , Milne, Roger L. , Pharoah, Paul D.P. , Goldgar, David E, Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , James, Paul , Lesueur, Fabienne , Peterlongo, Paolo , Teo, Soo H , Swerdlow, Anthony J , Campbell, Ian G , John, Esther M , Southey, Melissa C , Matsuo, Keitaro , Hart, Steven N , Dunning, Alison M , Jakubowska, Anna , Jones, Michael E , Lambrechts, Diether , Brenner, Hermann , Guénel, Pascal , Hartman, Mikael , Torres, Diana , García-Closas, Montserrat , Schmidt, Marjanka K , Michailidou, Kyriaki , Bogdanova, Natalia V , Benitez, Javier , Chenevix-Trench, Georgia , Zheng, Wei , Figueroa, Jonine D , Pylkäs, Katri , Devilee, Peter , Manoukian, Siranoush , Lubinski, Jan , Fletcher, Olivia , Bojesen, Stig E , Truong, Therese , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Kang, Daehee
Journal of Medical Genetics | April 22, 2016 | Volume: 53 | Issue: 5 | Pages: 298-309
Background BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. Methods We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. Results The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). Conclusions These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.
19p13.1 Is a Triple-Negative–Specific Breast Cancer Susceptibility Locus
Stevens, Kristen N., Fredericksen, Zachary, Vachon, Celine M. , Margolin, Sara , Lindblom, Annika , Nevanlinna, Heli , Greco, Dario , Aittomäki, Kristiina, Blomqvist, Carl , Chang‐Claude, Jenny , Vrieling, Alina , Flesch‐Janys, Dieter, Sinn, Hans‐Peter , Wang‐Gohrke, Shan , Nickels, Stefan , Brauch, Hiltrud , Ko, Yon‐Dschun, Fischer, Hans‐Peter , Schmutzler, Rita K., Meindl, Alfons, Bartram, Claus R., Schott, Sarah , Engel, Christoph , Weaver, JoEllen , Sharma, Priyanka , Brenner, Hermann , Stegmaier, Christa, Miron, Penelope , Yannoukakos, Drakoulis , Stavropoulou, Alexandra , Fountzilas, George , Swann, Ruth , Dwek, Miriam , Perkins, Annie, Zamora, María Pilar, Bojesen, Stig E. , Nielsen, Sune F. , Nordestgaard, Børge G. , Flyger, Henrik, Guénel, Pascal , Truong, Thérèse , Ménégaux, F. , Cordina‐Duverger, Emilie, Burwinkel, Barbara , Marmé, Frederick, Schneeweiß, Andreas , Sohn, Christof , Sawyer, Elinor J. , Tomlinson, Ian , Kerin, Michael J. , Peto, Julian , Johnson, Nichola , dos‐Santos‐Silva, Isabel , Fasching, Peter A. , Beckmann, Matthias W. , Hartmann, Arndt , Ekici, Arif B. , Lophatananon, Artitaya, Muir, Kenneth , Puttawibul, Puttisak, Wiangnon, Surapon , Schmidt, Marjanka K. , Braaf, Linde M., Rosenberg, Efraim H. , Hopper, John L. , Apicella, Carmel, Park, Daniel J. , Southey, Melissa C. , Swerdlow, Anthony J. , Ashworth, Alan , Orr, Nicholas, Schoemaker, Minouk J. , Dur, Christina Clarke, Shen, Chen‐Yang , Yu, Jyh-Cherng, Hsu, Huan-Ming, Hsiung, Chia‐Ni , Hamann, Ute , Dünnebier, Thomas, Rüdiger, Thomas , Ulmer, Hans Ulrich, Dunning, Alison M. , Humphreys, Manjeet K., Wang, Qin , Cox, Angela , Cross, Simon S. , Reed, Malcolm , Czene, Kamila , Ademuyiwa, Foluso O. , Hwang, Helena, Eccles, Diana M., García‐Closas, Montserrat , Figueroa, Jonine D. , Sherman, Mark E., Lissowska, Jolanta , Seynaeve, Caroline, Tollenaar, Rob A.�E.�M. , Hooning, Maartje J. , Andrulis, Irene L. , Knight, Julia A. , Glendon, Gord, Mulligan, Anna Marie , Winqvist, Robert , Pylkäs, Katri , Jukkola‐Vuorinen, Arja , Grip, Mervi, John, Esther M. , Miron, Alexander, Alnæs, Grethe Grenaker, Kristensen, Vessela, Børresen‐Dale, Anne‐Lise , Giles, Graham G. , Baglietto, Laura , McLean, Catriona , Severi, Gianluca , Kosel, Matthew L., Pankratz, V.S., Slager, Susan, Radice, Paolo , Peterlongo, Paolo , Manoukian, Siranoush , Barile, Monica, Lambrechts, Diether , Hatse, Sigrid , Dieudonné, Anne-Sophie, Christiaens, Marie-Rose, Chenevix‐Trench, Georgia , Chen, Xiaoqing, Mannermaa, Arto, Kosma, Veli‐Matti , Hartikainen, Jaana M. , Soini, Ylermi, Easton, Douglas F., Eccles, Diana , Orr, Nick , Thorne, Heather , Purrington, Kristen S. , Lambrechts, Diether , Vachon, Celine M. , Wang, Xianshu , Meindl, Alfons, Godwin, Andrew K. , Pathak, Harsh B. , Müller, Heiko , Arndt, Volker , Gogas, Helen J , Milne, Roger L. , Benı́tez, Javier , Pérez, José Ignacio Arias , Fletcher, Olivia , Broeks, Annegien , Orr, Nicholas, Anton‐Culver, Hoda , Ziogas, Argyrios , Bernstein, Leslie , Pharoah, Paul D.P. , Hall, Per N , Ambrosone, Christine B. , Eccles, Diana M., Devilee, Peter , Kristensen, Vessela N. , Kosel, Matthew , Olson, Janet E. , Beesley, Jonathan , Chen, Xiaoqing, Mannermaa, Arto, Couch, Fergus J. , Nevanlinna, H , Lambrechts, Diether , Giles, Graham G , Peterlongo, Paolo , Eccles, Diana , Swerdlow, Anthony J , Radice, Paolo , Lissowska, Jolanta , John, Esther M , Southey, Melissa C , Sinn, Peter , Muir, Kenneth , Dunning, Alison M , Lambrechts, Diether , Brenner, Hermann , Cox, Angela , Guénel, Pascal , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Hartikainen, Jaana M , Engel, Christoph , Chenevix-Trench, Georgia , Figueroa, Jonine D , Czene, Kamila , Ademuyiwa, Foluso O , Pylkäs, Katri , Yannoukakos, Drakoulis , Manoukian, Siranoush , Baglietto, Laura , Bojesen, Stig E , Purrington, Kristen S , Sharma, Priyanka , Schoemaker, Minouk J , Truong, Therese , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Sawyer, Elinor J , Orr, Nick
Cancer Research | February 13, 2012 | Volume: 72 | Issue: 7 | Pages: 1795-1803
Abstract The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05–1.15; P = 3.49 × 10−5] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13–1.31; P = 2.22 × 10−7). However, rs8170 was no longer associated with ER-negative breast cancer risk when triple-negative cases were excluded (OR, 0.98; 95% CI, 0.89–1.07; P = 0.62). In addition, a combined analysis of triple-negative cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC; N = 3,566) identified a genome-wide significant association between rs8170 and triple-negative breast cancer risk (OR, 1.25; 95% CI, 1.18–1.33; P = 3.31 × 10−13]. Thus, 19p13.1 is the first triple-negative–specific breast cancer risk locus and the first locus specific to a histologic subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple-negative tumors and other subtypes likely arise through distinct etiologic pathways. Cancer Res; 72(7); 1795–803. ©2012 AACR.
Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium
Schmidt, Marjanka K. , Sherman, Mark E., Hopper, John L. , Dite, Gillian S. , Apicella, Carmel, Smith, Letitia, Hammet, Fleur, Southey, Melissa C. , Veer, Laura van ‘t , Smit, Vincent T.H.B.M. , Fasching, Peter A. , Beckmann, Matthias W. , Jud, Sebastian M. , Ekici, Arif B. , Hartmann, Arndt , Hein, Alexander , Schulz-Wendtland, R., Burwinkel, Barbara , Schneeweiß, Andreas , Sinn, Hans‐Peter , Sohn, Christof , Tchatchou, Sandrine, Bojesen, Stig E. , Nordestgaard, Børge G. , Flyger, Henrik, Ørsted, David D., Kaur‐Knudsen, Diljit, Rodríguez, Primitiva Menéndez, Brauch, Hiltrud , Justenhoven, Christina , Ko, Yon‐Dschun, Network, The Genica, Hamann, Ute, Fischer, Hans‐Peter , Brüning, Thomas , Pesch, Beate, Chang‐Claude, Jenny , Wang‐Gohrke, Shan , Bremer, Michael , Karstens, Johann H., Hillemanns, Peter , Dörk, Thilo , Nevanlinna, Heli , Heikkinen, Tuomas , Blomqvist, Carl , Aittomäki, Kristiina, Aaltonen, Kirsimari, Lindblom, Annika , Margolin, Sara , Mannermaa, Arto, Kosma, Veli‐Matti , Kauppinen, Jaana M., Kataja, Vesa , Auvinen, Päivi , Eskelinen, Matti , Soini, Ylermi, Chenevix‐Trench, Georgia , Spurdle, Amanda B. , Beesley, Jonathan, Chen, Xiaoqing, Holland, Helene, kConFab, AOCS, Lambrechts, Diether , Claes, Bart, Vandorpe, T., Neven, Patrick , Wildiers, Hans , Flesch‐Janys, Dieter, Hein, Rebecca, Löning, Thomas , Kosel, Matthew , Fredericksen, Zachary S., Giles, Graham G. , Baglietto, Laura , Severi, Gianluca , McLean, Catriona , Haiman, Christopher A., Henderson, Brian E., Kolonel, Laurence N. , Alnæs, Grethe Grenaker, Kristensen, Vessela, Børresen‐Dale, Anne‐Lise , Hunter, David J. , Hankinson, Susan E. , Andrulis, Irene L. , Mulligan, Anna Marie , O’Malley, Frances P., Huijts, Petra E.A., Tollenaar, Rob A.�E.�M. , Seynaeve, Caroline, Lissowska, Jolanta , Brinton, Louise A. , Pepłońska, Beata , Yang, Xiaohong R. , Hooning, Maartje J. , Hollestelle, Antoinette , Oldenburg, Rogier A., Jager, Agnes , Kriege, Mieke, Ozturk, Bahar, Czene, Kamila , Humphreys, Keith , Liu, Jianjun , Cox, Angela , Connley, Daniel, Cramp, Helen, Balasubramanian, Sabapathy P. , Reed, Malcolm , Dunning, Alison M. , Easton, Douglas F., Humphreys, Manjeet K., Caldas, Carlos , Blows, Fiona M., Driver, Kristy, Provenzano, Elena , Lubiński, Jan , Jakubowska, Anna , Huzarski, Tomasz , Byrski, Tomasz , Górski, Bohdan , Brennan, Paul , Sangrajrang, Suleeporn , Gaborieau, Valérie , Shen, Chen‐Yang , Hsiung, Chia‐Ni , Yu, Jyh‐Cherng , Chen, Shou‐Tung , Hsu, Giu‐Cheng, Hou, Ming‐Feng , Huang, Chiun‐Sheng , García‐Closas, Montserrat , Thorne, Heather , Hartikainen, Jaana M. , Bowtell, David D.L. , Lambrechts, Diether , Broeks, Annegien , Couch, Fergus J. , Veer, Laura J. van’t , Groot, Renate H. M. de , Marmé, Frederik , Milne, Roger L. , Pérez, José Ignacio Arias , Zamora, Pilar M. , Benı́tez, Javier , Network, The Genica, Heikkilä, Päivi , Mannermaa, Arto, Chen, Xiaoqing, kConFab, AOCS, Wang, Xianshu , Marchand, Loı̈c Le , Kristensen, Vessela N. , Devilee, Peter , Asperen, Christi J. van , Chanock, Stephen Jacob , Figueroa, Jonine D. , Leenders, Geert J.L.H. van , Hall, Per N , Cross, Simon S. , Cybulski, Cezary , Gronwald, Jacek , Anton‐Culver, Hoda , Ziogas, Argyrios , Pharoah, Paul D.P. , Nevanlinna, H , Dörk, Thilo , Lambrechts, Diether , Giles, Graham G , Spurdle, Amanda B , Hein, Alexander , Hillemanns, Peter , Lissowska, Jolanta , Caldas, Carlos , Southey, Melissa C , Sinn, Peter , Dunning, Alison M , Jakubowska, Anna , Lambrechts, Diether , Cox, Angela , García-Closas, Montserrat , Schmidt, Marjanka K , Severi, Gianluca , Ekici, Arif B , Hartikainen, Jaana M , Chenevix-Trench, Georgia , Huzarski, Tomasz , Czene, Kamila , Bowtell, David D , Lubinski, Jan , Baglietto, Laura , Bojesen, Stig E , Huang, Chiun-Sheng , Wildiers, Hans , Mclean, Catriona , Brauch, Hiltrud , Lindblom, Annika , Liu, Jing
Human Molecular Genetics | May 19, 2011 | Volume: 20 | Issue: 16 | Pages: 3289-3303