Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
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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 P; Beesley, Jonathan; Amin Al Olama, Ali; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J; Thompson, Deborah J; Kibel, Adam S; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K; Gentry-Maharaj, Aleksandra; Whittemore, Alice S; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B; Burwinkel, Barbara; Karlan, Beth Y; Nordestgaard, Børge G; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B; Høgdall, Claus K; Teerlink, Craig C; Kang, Daehee; Tessier, Daniel C; Schaid, Daniel J; Stram, Daniel O; Cramer, Daniel W; Neal, David E; Eccles, Diana; Flesch-Janys, Dieter; Edwards, Digna R Velez; Wokozorczyk, Dominika; Levine, Douglas A; Yannoukakos, Drakoulis; Sawyer, Elinor J; Bandera, Elisa V; Poole, Elizabeth M; Goode, Ellen L; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C; Wiklund, Fredrik; Giles, Graham G; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A; Darabi, Hatef; Salvesen, Helga B; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L; Benítez, Javier; Doherty, Jennifer A; Permuth, Jennifer B; Chang-Claude, Jenny; Donovan, Jenny L; Dennis, Joe; Schildkraut, Joellen M; Schleutker, Johanna; Hopper, John L; Kupryjanczyk, Jolanta; Park, Jong Y; Figueroa, Jonine; Clements, Judith A; Knight, Julia A; Peto, Julian; Cunningham, Julie M; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A; Massuger, Leon F A G; Fitzgerald, Liesel M; Cook, Linda S; Cannon-Albright, Lisa; Hooning, Maartje J; Pike, Malcolm C; Bolla, Manjeet K; Luedeke, Manuel; Teixeira, Manuel R; Goodman, Marc T; Schmidt, Marjanka K; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A T; Hou, Ming-Feng; Schoemaker, Minouk J; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; 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; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K; Stephenson, Robert A; MacInnis, Robert J; Hoover, Robert N; Winqvist, Robert; Ness, Roberta; Milne, Roger L; Travis, Ruth C; Benlloch, Sara; Olson, Sara H; McDonnell, Shannon K; Tworoger, Shelley S; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N; Bojesen, Stig E; Gapstur, Susan M; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L J; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J; Edwards, Todd L; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L; Berchuck, Andrew; Dunning, Alison M; Simard, Jacques; Haiman, Christopher A; Spurdle, Amanda; Sellers, Thomas A; Hunter, David J; Henderson, Brian E; Kraft, Peter; Chanock, Stephen J; Couch, Fergus J; Hall, Per; Gayther, Simon A; Easton, Douglas F; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D P; Lambrechts, Diether; ABCTB Investigators.
In: CANCER DISCOV, Vol. 6, No. 9, 09.2016, p. 1052-67.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
AU - Kar, Siddhartha P
AU - Beesley, Jonathan
AU - Amin Al Olama, Ali
AU - Michailidou, Kyriaki
AU - Tyrer, Jonathan
AU - Kote-Jarai, ZSofia
AU - Lawrenson, Kate
AU - Lindstrom, Sara
AU - Ramus, Susan J
AU - Thompson, Deborah J
AU - Kibel, Adam S
AU - Dansonka-Mieszkowska, Agnieszka
AU - Michael, Agnieszka
AU - Dieffenbach, Aida K
AU - Gentry-Maharaj, Aleksandra
AU - Whittemore, Alice S
AU - Wolk, Alicja
AU - Monteiro, Alvaro
AU - Peixoto, Ana
AU - Kierzek, Andrzej
AU - Cox, Angela
AU - Rudolph, Anja
AU - Gonzalez-Neira, Anna
AU - Wu, Anna H
AU - Lindblom, Annika
AU - Swerdlow, Anthony
AU - Ziogas, Argyrios
AU - Ekici, Arif B
AU - Burwinkel, Barbara
AU - Karlan, Beth Y
AU - Nordestgaard, Børge G
AU - Blomqvist, Carl
AU - Phelan, Catherine
AU - McLean, Catriona
AU - Pearce, Celeste Leigh
AU - Vachon, Celine
AU - Cybulski, Cezary
AU - Slavov, Chavdar
AU - Stegmaier, Christa
AU - Maier, Christiane
AU - Ambrosone, Christine B
AU - Høgdall, Claus K
AU - Teerlink, Craig C
AU - Kang, Daehee
AU - Tessier, Daniel C
AU - Schaid, Daniel J
AU - Stram, Daniel O
AU - Cramer, Daniel W
AU - Neal, David E
AU - Eccles, Diana
AU - Flesch-Janys, Dieter
AU - Edwards, Digna R Velez
AU - Wokozorczyk, Dominika
AU - Levine, Douglas A
AU - Yannoukakos, Drakoulis
AU - Sawyer, Elinor J
AU - Bandera, Elisa V
AU - Poole, Elizabeth M
AU - Goode, Ellen L
AU - Khusnutdinova, Elza
AU - Høgdall, Estrid
AU - Song, Fengju
AU - Bruinsma, Fiona
AU - Heitz, Florian
AU - Modugno, Francesmary
AU - Hamdy, Freddie C
AU - Wiklund, Fredrik
AU - Giles, Graham G
AU - Olsson, Håkan
AU - Wildiers, Hans
AU - Ulmer, Hans-Ulrich
AU - Pandha, Hardev
AU - Risch, Harvey A
AU - Darabi, Hatef
AU - Salvesen, Helga B
AU - Nevanlinna, Heli
AU - Gronberg, Henrik
AU - Brenner, Hermann
AU - Brauch, Hiltrud
AU - Anton-Culver, Hoda
AU - Song, Honglin
AU - Lim, Hui-Yi
AU - McNeish, Iain
AU - Campbell, Ian
AU - Vergote, Ignace
AU - Gronwald, Jacek
AU - Lubiński, Jan
AU - Stanford, Janet L
AU - Benítez, Javier
AU - Doherty, Jennifer A
AU - Permuth, Jennifer B
AU - Chang-Claude, Jenny
AU - Donovan, Jenny L
AU - Dennis, Joe
AU - Schildkraut, Joellen M
AU - Schleutker, Johanna
AU - Hopper, John L
AU - Kupryjanczyk, Jolanta
AU - Park, Jong Y
AU - Figueroa, Jonine
AU - Clements, Judith A
AU - Knight, Julia A
AU - Peto, Julian
AU - Cunningham, Julie M
AU - Pow-Sang, Julio
AU - Batra, Jyotsna
AU - Czene, Kamila
AU - Lu, Karen H
AU - Herkommer, Kathleen
AU - Khaw, Kay-Tee
AU - Matsuo, Keitaro
AU - Muir, Kenneth
AU - Offitt, Kenneth
AU - Chen, Kexin
AU - Moysich, Kirsten B
AU - Aittomäki, Kristiina
AU - Odunsi, Kunle
AU - Kiemeney, Lambertus A
AU - Massuger, Leon F A G
AU - Fitzgerald, Liesel M
AU - Cook, Linda S
AU - Cannon-Albright, Lisa
AU - Hooning, Maartje J
AU - Pike, Malcolm C
AU - Bolla, Manjeet K
AU - Luedeke, Manuel
AU - Teixeira, Manuel R
AU - Goodman, Marc T
AU - Schmidt, Marjanka K
AU - Riggan, Marjorie
AU - Aly, Markus
AU - Rossing, Mary Anne
AU - Beckmann, Matthias W
AU - Moisse, Matthieu
AU - Sanderson, Maureen
AU - Southey, Melissa C
AU - Jones, Michael
AU - Lush, Michael
AU - Hildebrandt, Michelle A T
AU - Hou, Ming-Feng
AU - Schoemaker, Minouk J
AU - Garcia-Closas, Montserrat
AU - Bogdanova, Natalia
AU - Rahman, Nazneen
AU - Le, Nhu D
AU - Orr, Nick
AU - Wentzensen, Nicolas
AU - Pashayan, Nora
AU - Peterlongo, Paolo
AU - Guénel, Pascal
AU - Brennan, Paul
AU - Paulo, Paula
AU - Webb, Penelope M
AU - Broberg, Per
AU - Fasching, Peter A
AU - Devilee, Peter
AU - Wang, Qin
AU - Cai, Qiuyin
AU - Li, Qiyuan
AU - Kaneva, Radka
AU - Butzow, Ralf
AU - Kopperud, Reidun Kristin
AU - Schmutzler, Rita K
AU - Stephenson, Robert A
AU - MacInnis, Robert J
AU - Hoover, Robert N
AU - Winqvist, Robert
AU - Ness, Roberta
AU - Milne, Roger L
AU - Travis, Ruth C
AU - Benlloch, Sara
AU - Olson, Sara H
AU - McDonnell, Shannon K
AU - Tworoger, Shelley S
AU - Maia, Sofia
AU - Berndt, Sonja
AU - Lee, Soo Chin
AU - Teo, Soo-Hwang
AU - Thibodeau, Stephen N
AU - Bojesen, Stig E
AU - Gapstur, Susan M
AU - Kjær, Susanne Krüger
AU - Pejovic, Tanja
AU - Tammela, Teuvo L J
AU - Dörk, Thilo
AU - Brüning, Thomas
AU - Wahlfors, Tiina
AU - Key, Tim J
AU - Edwards, Todd L
AU - Menon, Usha
AU - Hamann, Ute
AU - Mitev, Vanio
AU - Kosma, Veli-Matti
AU - Setiawan, Veronica Wendy
AU - Kristensen, Vessela
AU - Arndt, Volker
AU - Vogel, Walther
AU - Zheng, Wei
AU - Sieh, Weiva
AU - Blot, William J
AU - Kluzniak, Wojciech
AU - Shu, Xiao-Ou
AU - Gao, Yu-Tang
AU - Schumacher, Fredrick
AU - Freedman, Matthew L
AU - Berchuck, Andrew
AU - Dunning, Alison M
AU - Simard, Jacques
AU - Haiman, Christopher A
AU - Spurdle, Amanda
AU - Sellers, Thomas A
AU - Hunter, David J
AU - Henderson, Brian E
AU - Kraft, Peter
AU - Chanock, Stephen J
AU - Couch, Fergus J
AU - Hall, Per
AU - Gayther, Simon A
AU - Easton, Douglas F
AU - Chenevix-Trench, Georgia
AU - Eeles, Rosalind
AU - Pharoah, Paul D P
AU - Lambrechts, Diether
AU - ABCTB Investigators
AU - Harth, Volker
N1 - ©2016 American Association for Cancer Research.
PY - 2016/9
Y1 - 2016/9
N2 - UNLABELLED: 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.
AB - UNLABELLED: 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.
KW - Journal Article
U2 - 10.1158/2159-8290.CD-15-1227
DO - 10.1158/2159-8290.CD-15-1227
M3 - SCORING: Journal article
C2 - 27432226
VL - 6
SP - 1052
EP - 1067
JO - CANCER DISCOV
JF - CANCER DISCOV
SN - 2159-8274
IS - 9
ER -
