Genome-wide meta-analyses of breast, ovarian, and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types

Siddhartha P. Kar, Jonathan Beesley, Ali Amin Al Olama, Kyriaki Michailidou, Jonathan Tyrer, Zsofi A. Kote-Jarai, Kate Lawrenson, Sara Lindstrom, Susan J. Ramus, Deborah J. Thompson, Adam S. Kibel, Agnieszka Dansonka-Mieszkowska, Agnieszka Michael, Aida K. Dieffenbach, Aleksandra Gentry-Maharaj, Alice S. Whittemore, Alicja Wolk, Alvaro Monteiro, Ana Peixoto, Andrzej KierzekAngela Cox, Anja Rudolph, Anna Gonzalez-Neira, Anna H. Wu, Annika Lindblom, Anthony Swerdlow, Argyrios Ziogas, Arif B. Ekici, Barbara Burwinkel, Beth Y. Karlan, Borge G. Nordestgaard, Carl Blomqvist, Catherine Phelan, Catriona McLean, Celeste Leigh Pearce, Celine Vachon, Cezary Cybulski, Chavdar Slavov, Christa Stegmaier, Christiane Maier, Christine B. Ambrosone, Claus K. Hogdall, Craig C. Teerlink, Daehee Kang, Daniel C. Tessier, Daniel J. Schaid, Daniel O. Stram, Daniel W. Cramer, David E. Neal, Diana Eccles, Dieter Flesch-Janys, Digna R. Velez Edwards, Dominika Wokozorczyk, Douglas A. Levine, Drakoulis Yannoukakos, Elinor J. Sawyer, Elisa V. Bandera, Elizabeth M. Poole, Ellen L. Goode, Elza Khusnutdinova, Estrid Hogdall, Fengju Song, Fiona Bruinsma, Florian Heitz, Francesmary Modugno, Freddie C. Hamdy, Fredrik Wiklund, Graham G. Giles, Hakan Olsson, Hans Wildiers, Hans Ulrich Ulmer, Hardev Pandha, Harvey A. Risch, Hatef Darabi, Helga B. Salvesen, Heli Nevanlinna, Henrik Gronberg, Hermann Brenner, Hiltrud Brauch, Hoda Anton-Culver, Honglin Song, Hui Yi Lim, Iain McNeish, Ian Campbell, Ignace Vergote, Jacek Gronwald, Jan Lubiński, Janet L. Stanford, Javier Benitez, Jennifer A. Doherty, Jennifer B. Permuth, Jenny Chang-Claude, Jenny L. Donovan, Joe Dennis, Joellen M. Schildkraut, Johanna Schleutker, John L. Hopper, Jolanta Kupryjanczyk, Jong Y. Park, Jonine Figueroa, Judith A. Clements, Julia A. Knight, Julian Peto, Julie M. Cunningham, Julio Pow-Sang, Jyotsna Batra, Kamila Czene, Karen H. Lu, Kathleen Herkommer, Kay Tee Khaw, Keitaro Matsuo, Kenneth Muir, Kenneth Offitt, Kexin Chen, Kirsten B. Moysich, Kristiina Aittomaki, Kunle Odunsi, Lambertus A. Kiemeney, Leon F A G Massuger, Liesel M. Fitzgerald, Linda S. Cook, Lisa Cannon-Albright, Maartje J. Hooning, Malcolm C. Pike, Manjeet K. Bolla, Manuel Luedeke, Manuel R. Teixeira, Marc T. Goodman, Marjanka K. Schmidt, Marjorie Riggan, Markus Aly, Mary Anne Rossing, Matthias W. Beckmann, Matthieu Moisse, Maureen Sanderson, Melissa C. Southey, Michael Jones, Michael Lush, Michelle A T Hildebrandt, Ming Feng Hou, Minouk J. Schoemaker, Montserrat Garcia-Closas, Natalia Bogdanova, Nazneen Rahman, Nhu D. Le, Nick Orr, Nicolas Wentzensen, Nora Pashayan, Paolo Peterlongo, Pascal Guenel, Paul Brennan, Paula Paulo, Penelope M. Webb, Per Broberg, Peter A. Fasching, Peter Devilee, Qin Wang, Qiuyin Cai, Qiyuan Li, Radka Kaneva, Ralf Butzow, Reidun Kristin Kopperud, Rita K. Schmutzler, Robert A. Stephenson, Robert J. Macinnis, Robert N. Hoover, Robert Winqvist, Roberta Ness, Roger L. Milne, Ruth C. Travis, Sara Benlloch, Sara H. Olson, Shannon K. McDonnell, Shelley S. Tworoger, Sofia Maia, Sonja Berndt, Soo Chin Lee, Soo Hwang Teo, Stephen N. Thibodeau, Stig E. Bojesen, Susan M. Gapstur, Susanne Kruger Kjar, Tanja Pejovic, Teuvo L J Tammela, A. Eeles, Douglas Easton, Z. Sofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth Muir, Graham G. Giles, Melissa C. Southey, Liesel M. Fitzgerald, Henrik Gronberg, Fredrik Wiklund, Markus Aly, Brian E. Henderson, Fredrick Schumacher, Christopher A. Haiman, Johanna Schleutker, Tiina Wahlfors, Teuvo L J Tammela, Børge G. Nordestgaard, Tim J. Key, Ruth C. Travis, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Paul Pharoah, Nora Pashayan, Kay Tee Khaw, Janet L. Stanford, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Christiane Maier, Walther Vogel, Manuel Luedeke, Kathleen Herkommer, Adam S. Kibel, Cezary Cybulski, Dominika Wokozorczyk, Wojciech Kluzniak, Lisa Cannon-Albright, Hermann Brenner, Aida K. Dieffenbach, Volker Arndt, Jong Y. Park, Thomas Sellers, Hui Yi Lim, Chavdar Slavov, Radka Kaneva, Vanio Mitev, Jyotsna Batra, Amanda Spurdle, Manuel R. Teixeira, Paula Paulo, Sofia Maia, Hardev Pandha, Agnieszka Michael, Andrzej Kierzek, Thilo Dork, Thomas Bruning, Tiina Wahlfors, Tim J. Key, Todd L. Edwards, Usha Menon, Ute Hamann, Vanio Mitev, Veli Matti Kosma, Veronica Wendy Setiawan, Vessela Kristensen, Volker Arndt, Walther Vogel, Wei Zheng, Weiva Sieh, William J. Blot, Wojciech Kluzniak, Xiao Ou Shu, Yu Tang Gao, Fredrick Schumacher, Matthew L. Freedman, Andrew Berchuck, Alison M. Dunning, Jacques Simard, Christopher A. Haiman, Amanda Spurdle, Thomas A. Sellers, David J. Hunter, Brian E. Henderson, Peter Kraft, Stephen J. Chanock, Fergus J. Couch, Per Hall, Simon A. Gayther, Douglas F. Easton, Georgia Chenevix-Trench, Rosalind Eeles, Paul D P Pharoah, Diether Lambrechts

Research output: Contribution to journalArticle

62 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1052-1067
Number of pages16
JournalCancer Discovery
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2016

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Ovarian Neoplasms
Meta-Analysis
Prostatic Neoplasms
Genome
Breast Neoplasms
Neoplasms
Genome-Wide Association Study
Hormones
Molecular Sequence Annotation
Death Domain Receptors
Second Primary Neoplasms
Quantitative Trait Loci
Genes

ASJC Scopus subject areas

  • Oncology

Cite this

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; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, Zsofi A.; 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, Borge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Hogdall, 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; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Hogdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Hakan; 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.; Benitez, 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.; Aittomaki, 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; Guenel, 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.; Kjar, Susanne Kruger; Pejovic, Tanja; Tammela, Teuvo L J; Eeles, A.; Easton, Douglas; Kote-Jarai, Z. Sofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G.; Southey, Melissa C.; Fitzgerald, Liesel M.; Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Henderson, Brian E.; Schumacher, Fredrick; Haiman, Christopher A.; Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo L J; Nordestgaard, Børge G.; Key, Tim J.; Travis, Ruth C.; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Pharoah, Paul; Pashayan, Nora; Khaw, Kay Tee; Stanford, Janet L.; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Maier, Christiane; Vogel, Walther; Luedeke, Manuel; Herkommer, Kathleen; Kibel, Adam S.; Cybulski, Cezary; Wokozorczyk, Dominika; Kluzniak, Wojciech; Cannon-Albright, Lisa; Brenner, Hermann; Dieffenbach, Aida K.; Arndt, Volker; Park, Jong Y.; Sellers, Thomas; Lim, Hui Yi; Slavov, Chavdar; Kaneva, Radka; Mitev, Vanio; Batra, Jyotsna; Spurdle, Amanda; Teixeira, Manuel R.; Paulo, Paula; Maia, Sofia; Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Dork, Thilo; Bruning, 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.

In: Cancer Discovery, Vol. 6, No. 9, 01.09.2016, p. 1052-1067.

Research output: Contribution to journalArticle

Kar, SP, Beesley, J, Al Olama, AA, Michailidou, K, Tyrer, J, Kote-Jarai, ZA, Lawrenson, K, Lindstrom, S, Ramus, SJ, Thompson, DJ, Kibel, AS, Dansonka-Mieszkowska, A, Michael, A, Dieffenbach, AK, Gentry-Maharaj, A, Whittemore, AS, Wolk, A, Monteiro, A, Peixoto, A, Kierzek, A, Cox, A, Rudolph, A, Gonzalez-Neira, A, Wu, AH, Lindblom, A, Swerdlow, A, Ziogas, A, Ekici, AB, Burwinkel, B, Karlan, BY, Nordestgaard, BG, Blomqvist, C, Phelan, C, McLean, C, Pearce, CL, Vachon, C, Cybulski, C, Slavov, C, Stegmaier, C, Maier, C, Ambrosone, CB, Hogdall, CK, Teerlink, CC, Kang, D, Tessier, DC, Schaid, DJ, Stram, DO, Cramer, DW, Neal, DE, Eccles, D, Flesch-Janys, D, Velez Edwards, DR, Wokozorczyk, D, Levine, DA, Yannoukakos, D, Sawyer, EJ, Bandera, EV, Poole, EM, Goode, EL, Khusnutdinova, E, Hogdall, E, Song, F, Bruinsma, F, Heitz, F, Modugno, F, Hamdy, FC, Wiklund, F, Giles, GG, Olsson, H, Wildiers, H, Ulmer, HU, Pandha, H, Risch, HA, Darabi, H, Salvesen, HB, Nevanlinna, H, Gronberg, H, Brenner, H, Brauch, H, Anton-Culver, H, Song, H, Lim, HY, McNeish, I, Campbell, I, Vergote, I, Gronwald, J, Lubiński, J, Stanford, JL, Benitez, J, Doherty, JA, Permuth, JB, Chang-Claude, J, Donovan, JL, Dennis, J, Schildkraut, JM, Schleutker, J, Hopper, JL, Kupryjanczyk, J, Park, JY, Figueroa, J, Clements, JA, Knight, JA, Peto, J, Cunningham, JM, Pow-Sang, J, Batra, J, Czene, K, Lu, KH, Herkommer, K, Khaw, KT, Matsuo, K, Muir, K, Offitt, K, Chen, K, Moysich, KB, Aittomaki, K, Odunsi, K, Kiemeney, LA, Massuger, LFAG, Fitzgerald, LM, Cook, LS, Cannon-Albright, L, Hooning, MJ, Pike, MC, Bolla, MK, Luedeke, M, Teixeira, MR, Goodman, MT, Schmidt, MK, Riggan, M, Aly, M, Rossing, MA, Beckmann, MW, Moisse, M, Sanderson, M, Southey, MC, Jones, M, Lush, M, Hildebrandt, MAT, Hou, MF, Schoemaker, MJ, Garcia-Closas, M, Bogdanova, N, Rahman, N, Le, ND, Orr, N, Wentzensen, N, Pashayan, N, Peterlongo, P, Guenel, P, Brennan, P, Paulo, P, Webb, PM, Broberg, P, Fasching, PA, Devilee, P, Wang, Q, Cai, Q, Li, Q, Kaneva, R, Butzow, R, Kopperud, RK, Schmutzler, RK, Stephenson, RA, Macinnis, RJ, Hoover, RN, Winqvist, R, Ness, R, Milne, RL, Travis, RC, Benlloch, S, Olson, SH, McDonnell, SK, Tworoger, SS, Maia, S, Berndt, S, Lee, SC, Teo, SH, Thibodeau, SN, Bojesen, SE, Gapstur, SM, Kjar, SK, Pejovic, T, Tammela, TLJ, Eeles, A, Easton, D, Kote-Jarai, ZS, Al Olama, AA, Benlloch, S, Muir, K, Giles, GG, Southey, MC, Fitzgerald, LM, Gronberg, H, Wiklund, F, Aly, M, Henderson, BE, Schumacher, F, Haiman, CA, Schleutker, J, Wahlfors, T, Tammela, TLJ, Nordestgaard, BG, Key, TJ, Travis, RC, Neal, DE, Donovan, JL, Hamdy, FC, Pharoah, P, Pashayan, N, Khaw, KT, Stanford, JL, Thibodeau, SN, McDonnell, SK, Schaid, DJ, Maier, C, Vogel, W, Luedeke, M, Herkommer, K, Kibel, AS, Cybulski, C, Wokozorczyk, D, Kluzniak, W, Cannon-Albright, L, Brenner, H, Dieffenbach, AK, Arndt, V, Park, JY, Sellers, T, Lim, HY, Slavov, C, Kaneva, R, Mitev, V, Batra, J, Spurdle, A, Teixeira, MR, Paulo, P, Maia, S, Pandha, H, Michael, A, Kierzek, A, Dork, T, Bruning, T, Wahlfors, T, Key, TJ, Edwards, TL, Menon, U, Hamann, U, Mitev, V, Kosma, VM, Setiawan, VW, Kristensen, V, Arndt, V, Vogel, W, Zheng, W, Sieh, W, Blot, WJ, Kluzniak, W, Shu, XO, Gao, YT, Schumacher, F, Freedman, ML, Berchuck, A, Dunning, AM, Simard, J, Haiman, CA, Spurdle, A, Sellers, TA, Hunter, DJ, Henderson, BE, Kraft, P, Chanock, SJ, Couch, FJ, Hall, P, Gayther, SA, Easton, DF, Chenevix-Trench, G, Eeles, R, Pharoah, PDP & Lambrechts, D 2016, 'Genome-wide meta-analyses of breast, ovarian, and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types', Cancer Discovery, vol. 6, no. 9, pp. 1052-1067. https://doi.org/10.1158/2159-8290.CD-15-1227
Kar, Siddhartha P. ; Beesley, Jonathan ; Al Olama, Ali Amin ; Michailidou, Kyriaki ; Tyrer, Jonathan ; Kote-Jarai, Zsofi A. ; 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, Borge G. ; Blomqvist, Carl ; Phelan, Catherine ; McLean, Catriona ; Pearce, Celeste Leigh ; Vachon, Celine ; Cybulski, Cezary ; Slavov, Chavdar ; Stegmaier, Christa ; Maier, Christiane ; Ambrosone, Christine B. ; Hogdall, 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 ; Velez Edwards, Digna R. ; Wokozorczyk, Dominika ; Levine, Douglas A. ; Yannoukakos, Drakoulis ; Sawyer, Elinor J. ; Bandera, Elisa V. ; Poole, Elizabeth M. ; Goode, Ellen L. ; Khusnutdinova, Elza ; Hogdall, Estrid ; Song, Fengju ; Bruinsma, Fiona ; Heitz, Florian ; Modugno, Francesmary ; Hamdy, Freddie C. ; Wiklund, Fredrik ; Giles, Graham G. ; Olsson, Hakan ; 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. ; Benitez, 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. ; Aittomaki, 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 ; Guenel, 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. ; Kjar, Susanne Kruger ; Pejovic, Tanja ; Tammela, Teuvo L J ; Eeles, A. ; Easton, Douglas ; Kote-Jarai, Z. Sofia ; Al Olama, Ali Amin ; Benlloch, Sara ; Muir, Kenneth ; Giles, Graham G. ; Southey, Melissa C. ; Fitzgerald, Liesel M. ; Gronberg, Henrik ; Wiklund, Fredrik ; Aly, Markus ; Henderson, Brian E. ; Schumacher, Fredrick ; Haiman, Christopher A. ; Schleutker, Johanna ; Wahlfors, Tiina ; Tammela, Teuvo L J ; Nordestgaard, Børge G. ; Key, Tim J. ; Travis, Ruth C. ; Neal, David E. ; Donovan, Jenny L. ; Hamdy, Freddie C. ; Pharoah, Paul ; Pashayan, Nora ; Khaw, Kay Tee ; Stanford, Janet L. ; Thibodeau, Stephen N. ; McDonnell, Shannon K. ; Schaid, Daniel J. ; Maier, Christiane ; Vogel, Walther ; Luedeke, Manuel ; Herkommer, Kathleen ; Kibel, Adam S. ; Cybulski, Cezary ; Wokozorczyk, Dominika ; Kluzniak, Wojciech ; Cannon-Albright, Lisa ; Brenner, Hermann ; Dieffenbach, Aida K. ; Arndt, Volker ; Park, Jong Y. ; Sellers, Thomas ; Lim, Hui Yi ; Slavov, Chavdar ; Kaneva, Radka ; Mitev, Vanio ; Batra, Jyotsna ; Spurdle, Amanda ; Teixeira, Manuel R. ; Paulo, Paula ; Maia, Sofia ; Pandha, Hardev ; Michael, Agnieszka ; Kierzek, Andrzej ; Dork, Thilo ; Bruning, 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. / Genome-wide meta-analyses of breast, ovarian, and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types. In: Cancer Discovery. 2016 ; Vol. 6, No. 9. pp. 1052-1067.
@article{356730f3f5e7454783944aaaceb97cea,
title = "Genome-wide meta-analyses of breast, ovarian, and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types",
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.",
author = "Kar, {Siddhartha P.} and Jonathan Beesley and {Al Olama}, {Ali Amin} and Kyriaki Michailidou and Jonathan Tyrer and Kote-Jarai, {Zsofi A.} and Kate Lawrenson and Sara Lindstrom and Ramus, {Susan J.} and Thompson, {Deborah J.} and Kibel, {Adam S.} and Agnieszka Dansonka-Mieszkowska and Agnieszka Michael and Dieffenbach, {Aida K.} and Aleksandra Gentry-Maharaj and Whittemore, {Alice S.} and Alicja Wolk and Alvaro Monteiro and Ana Peixoto and Andrzej Kierzek and Angela Cox and Anja Rudolph and Anna Gonzalez-Neira and Wu, {Anna H.} and Annika Lindblom and Anthony Swerdlow and Argyrios Ziogas and Ekici, {Arif B.} and Barbara Burwinkel and Karlan, {Beth Y.} and Nordestgaard, {Borge G.} and Carl Blomqvist and Catherine Phelan and Catriona McLean and Pearce, {Celeste Leigh} and Celine Vachon and Cezary Cybulski and Chavdar Slavov and Christa Stegmaier and Christiane Maier and Ambrosone, {Christine B.} and Hogdall, {Claus K.} and Teerlink, {Craig C.} and Daehee Kang and Tessier, {Daniel C.} and Schaid, {Daniel J.} and Stram, {Daniel O.} and Cramer, {Daniel W.} and Neal, {David E.} and Diana Eccles and Dieter Flesch-Janys and {Velez Edwards}, {Digna R.} and Dominika Wokozorczyk and Levine, {Douglas A.} and Drakoulis Yannoukakos and Sawyer, {Elinor J.} and Bandera, {Elisa V.} and Poole, {Elizabeth M.} and Goode, {Ellen L.} and Elza Khusnutdinova and Estrid Hogdall and Fengju Song and Fiona Bruinsma and Florian Heitz and Francesmary Modugno and Hamdy, {Freddie C.} and Fredrik Wiklund and Giles, {Graham G.} and Hakan Olsson and Hans Wildiers and Ulmer, {Hans Ulrich} and Hardev Pandha and Risch, {Harvey A.} and Hatef Darabi and Salvesen, {Helga B.} and Heli Nevanlinna and Henrik Gronberg and Hermann Brenner and Hiltrud Brauch and Hoda Anton-Culver and Honglin Song and Lim, {Hui Yi} and Iain McNeish and Ian Campbell and Ignace Vergote and Jacek Gronwald and Jan Lubiński and Stanford, {Janet L.} and Javier Benitez and Doherty, {Jennifer A.} and Permuth, {Jennifer B.} and Jenny Chang-Claude and Donovan, {Jenny L.} and Joe Dennis and Schildkraut, {Joellen M.} and Johanna Schleutker and Hopper, {John L.} and Jolanta Kupryjanczyk and Park, {Jong Y.} and Jonine Figueroa and Clements, {Judith A.} and Knight, {Julia A.} and Julian Peto and Cunningham, {Julie M.} and Julio Pow-Sang and Jyotsna Batra and Kamila Czene and Lu, {Karen H.} and Kathleen Herkommer and Khaw, {Kay Tee} and Keitaro Matsuo and Kenneth Muir and Kenneth Offitt and Kexin Chen and Moysich, {Kirsten B.} and Kristiina Aittomaki and Kunle Odunsi and Kiemeney, {Lambertus A.} and Massuger, {Leon F A G} and Fitzgerald, {Liesel M.} and Cook, {Linda S.} and Lisa Cannon-Albright and Hooning, {Maartje J.} and Pike, {Malcolm C.} and Bolla, {Manjeet K.} and Manuel Luedeke and Teixeira, {Manuel R.} and Goodman, {Marc T.} and Schmidt, {Marjanka K.} and Marjorie Riggan and Markus Aly and Rossing, {Mary Anne} and Beckmann, {Matthias W.} and Matthieu Moisse and Maureen Sanderson and Southey, {Melissa C.} and Michael Jones and Michael Lush and Hildebrandt, {Michelle A T} and Hou, {Ming Feng} and Schoemaker, {Minouk J.} and Montserrat Garcia-Closas and Natalia Bogdanova and Nazneen Rahman and Le, {Nhu D.} and Nick Orr and Nicolas Wentzensen and Nora Pashayan and Paolo Peterlongo and Pascal Guenel and Paul Brennan and Paula Paulo and Webb, {Penelope M.} and Per Broberg and Fasching, {Peter A.} and Peter Devilee and Qin Wang and Qiuyin Cai and Qiyuan Li and Radka Kaneva and Ralf Butzow and Kopperud, {Reidun Kristin} and Schmutzler, {Rita K.} and Stephenson, {Robert A.} and Macinnis, {Robert J.} and Hoover, {Robert N.} and Robert Winqvist and Roberta Ness and Milne, {Roger L.} and Travis, {Ruth C.} and Sara Benlloch and Olson, {Sara H.} and McDonnell, {Shannon K.} and Tworoger, {Shelley S.} and Sofia Maia and Sonja Berndt and Lee, {Soo Chin} and Teo, {Soo Hwang} and Thibodeau, {Stephen N.} and Bojesen, {Stig E.} and Gapstur, {Susan M.} and Kjar, {Susanne Kruger} and Tanja Pejovic and Tammela, {Teuvo L J} and A. Eeles and Douglas Easton and Kote-Jarai, {Z. Sofia} and {Al Olama}, {Ali Amin} and Sara Benlloch and Kenneth Muir and Giles, {Graham G.} and Southey, {Melissa C.} and Fitzgerald, {Liesel M.} and Henrik Gronberg and Fredrik Wiklund and Markus Aly and Henderson, {Brian E.} and Fredrick Schumacher and Haiman, {Christopher A.} and Johanna Schleutker and Tiina Wahlfors and Tammela, {Teuvo L J} and Nordestgaard, {B{\o}rge G.} and Key, {Tim J.} and Travis, {Ruth C.} and Neal, {David E.} and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Paul Pharoah and Nora Pashayan and Khaw, {Kay Tee} and Stanford, {Janet L.} and Thibodeau, {Stephen N.} and McDonnell, {Shannon K.} and Schaid, {Daniel J.} and Christiane Maier and Walther Vogel and Manuel Luedeke and Kathleen Herkommer and Kibel, {Adam S.} and Cezary Cybulski and Dominika Wokozorczyk and Wojciech Kluzniak and Lisa Cannon-Albright and Hermann Brenner and Dieffenbach, {Aida K.} and Volker Arndt and Park, {Jong Y.} and Thomas Sellers and Lim, {Hui Yi} and Chavdar Slavov and Radka Kaneva and Vanio Mitev and Jyotsna Batra and Amanda Spurdle and Teixeira, {Manuel R.} and Paula Paulo and Sofia Maia and Hardev Pandha and Agnieszka Michael and Andrzej Kierzek and Thilo Dork and Thomas Bruning and Tiina Wahlfors and Key, {Tim J.} and Edwards, {Todd L.} and Usha Menon and Ute Hamann and Vanio Mitev and Kosma, {Veli Matti} and Setiawan, {Veronica Wendy} and Vessela Kristensen and Volker Arndt and Walther Vogel and Wei Zheng and Weiva Sieh and Blot, {William J.} and Wojciech Kluzniak and Shu, {Xiao Ou} and Gao, {Yu Tang} and Fredrick Schumacher and Freedman, {Matthew L.} and Andrew Berchuck and Dunning, {Alison M.} and Jacques Simard and Haiman, {Christopher A.} and Amanda Spurdle and Sellers, {Thomas A.} and Hunter, {David J.} and Henderson, {Brian E.} and Peter Kraft and Chanock, {Stephen J.} and Couch, {Fergus J.} and Per Hall and Gayther, {Simon A.} and Easton, {Douglas F.} and Georgia Chenevix-Trench and Rosalind Eeles and Pharoah, {Paul D P} and Diether Lambrechts",
year = "2016",
month = "9",
day = "1",
doi = "10.1158/2159-8290.CD-15-1227",
language = "English (US)",
volume = "6",
pages = "1052--1067",
journal = "Cancer Discovery",
issn = "2159-8274",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

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 - Al Olama, Ali Amin

AU - Michailidou, Kyriaki

AU - Tyrer, Jonathan

AU - Kote-Jarai, Zsofi A.

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, Borge 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 - Hogdall, 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 - Velez Edwards, Digna R.

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 - Hogdall, 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, Hakan

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 - Benitez, 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 - Aittomaki, 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 - Guenel, 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 - Kjar, Susanne Kruger

AU - Pejovic, Tanja

AU - Tammela, Teuvo L J

AU - Eeles, A.

AU - Easton, Douglas

AU - Kote-Jarai, Z. Sofia

AU - Al Olama, Ali Amin

AU - Benlloch, Sara

AU - Muir, Kenneth

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - Fitzgerald, Liesel M.

AU - Gronberg, Henrik

AU - Wiklund, Fredrik

AU - Aly, Markus

AU - Henderson, Brian E.

AU - Schumacher, Fredrick

AU - Haiman, Christopher A.

AU - Schleutker, Johanna

AU - Wahlfors, Tiina

AU - Tammela, Teuvo L J

AU - Nordestgaard, Børge G.

AU - Key, Tim J.

AU - Travis, Ruth C.

AU - Neal, David E.

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Pharoah, Paul

AU - Pashayan, Nora

AU - Khaw, Kay Tee

AU - Stanford, Janet L.

AU - Thibodeau, Stephen N.

AU - McDonnell, Shannon K.

AU - Schaid, Daniel J.

AU - Maier, Christiane

AU - Vogel, Walther

AU - Luedeke, Manuel

AU - Herkommer, Kathleen

AU - Kibel, Adam S.

AU - Cybulski, Cezary

AU - Wokozorczyk, Dominika

AU - Kluzniak, Wojciech

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Dieffenbach, Aida K.

AU - Arndt, Volker

AU - Park, Jong Y.

AU - Sellers, Thomas

AU - Lim, Hui Yi

AU - Slavov, Chavdar

AU - Kaneva, Radka

AU - Mitev, Vanio

AU - Batra, Jyotsna

AU - Spurdle, Amanda

AU - Teixeira, Manuel R.

AU - Paulo, Paula

AU - Maia, Sofia

AU - Pandha, Hardev

AU - Michael, Agnieszka

AU - Kierzek, Andrzej

AU - Dork, Thilo

AU - Bruning, 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

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85012028638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85012028638&partnerID=8YFLogxK

U2 - 10.1158/2159-8290.CD-15-1227

DO - 10.1158/2159-8290.CD-15-1227

M3 - Article

C2 - 27432226

AN - SCOPUS:85012028638

VL - 6

SP - 1052

EP - 1067

JO - Cancer Discovery

JF - Cancer Discovery

SN - 2159-8274

IS - 9

ER -