Kar, S. P., Beesley, J., Al Olama, A. A., Michailidou, K., Tyrer, J., Kote-Jarai, Z. A., Lawrenson, K., Lindstrom, S., Ramus, S. J., Thompson, D. J., Kibel, A. S., Dansonka-Mieszkowska, A., Michael, A., Dieffenbach, A. K., Gentry-Maharaj, A., Whittemore, A. S., Wolk, A., Monteiro, A., Peixoto, A., Kierzek, A., Cox, A., Rudolph, A., Gonzalez-Neira, A., Wu, A. H., Lindblom, A., Swerdlow, A., Ziogas, A., Ekici, A. B., Burwinkel, B., Karlan, B. Y., Nordestgaard, B. G., Blomqvist, C., Phelan, C., McLean, C., Pearce, C. L., Vachon, C., Cybulski, C., Slavov, C., Stegmaier, C., Maier, C., Ambrosone, C. B., Hogdall, C. K., Teerlink, C. C., Kang, D., Tessier, D. C., Schaid, D. J., Stram, D. O., Cramer, D. W., Neal, D. E., Eccles, D., Flesch-Janys, D., Edwards, D. R. V., Wokozorczyk, D., Levine, D. A., Yannoukakos, D., Sawyer, E. J., Bandera, E. V., Poole, E. M., Goode, E. L., Khusnutdinova, E., Hogdall, E., Song, F. J., Bruinsma, F., Heitz, F., Modugno, F., Hamdy, F. C., Wiklund, F., Giles, G. G., Olsson, H., Wildiers, H., Ulmer, H. U., Pandha, H., Risch, H. A., Darabi, H., Salvesen, H. B., Nevanlinna, H., Gronberg, H., Brenner, H., Brauch, H., Anton-Culver, H., Song, H. L., Lim, H. Y., McNeish, I., Campbell, I., Vergote, I., Gronwald, J., Lubinski, J., Stanford, J. L., Bentez, J., Doherty, J. A., Permuth, J. B., Chang-Claude, J., Donovan, J. L., Dennis, J., Schildkraut, J. M., Schleutker, J., Hopper, J. L., Kupryjanczyk, J., Park, J. Y., Figueroa, J., Clements, J. A., Knight, J. A., Peto, J., Cunningham, J. M., Pow-Sang, J., Batra, J., Czene, K., Lu, K. H., Herkommer, K., Khaw, K. T., Matsuo, K., Muir, K., Offitt, K., Chen, K. X., Moysich, K. B., Aittomaki, K., Odunsi, K., Kiemeney, L. A., Massuger, Lfag, Fitzgerald, L. M., Cook, L. S., Cannon-Albright, L., Hooning, M. J., Pike, M. C., Bolla, M. K., Luedeke, M., Teixeira, M. R., Goodman, M. T., Schmidt, M. K., Riggan, M., Aly, M., Rossing, M. A., Beckmann, M. W., Moisse, M., Sanderson, M., Southey, M. C., Jones, M., Lush, M., Hildebrandt, M. A. T., Hou, M. F., Schoemaker, M. J., Garcia-Closas, M., Bogdanova, N., Rahman, N., Le, N. D., Orr, N., Wentzensen, N., Pashayan, N., Peterlongo, P., Guenel, P., Brennan, P., Paulo, P., Webb, P. M., Broberg, P., Fasching, P. A., Devilee, P., Wang, Q., Cai, Q. Y., Li, Q. Y., Kaneva, R., Butzow, R., Kopperud, R. K., Schmutzler, R. K., Stephenson, R. A., MacInnis, R. J., Hoover, R. N., Winqvist, R., Ness, R., Milne, R. L., Travis, R. C., Benlloch, S., Olson, S. H., McDonnell, S. K., Tworoger, S. S., Maia, S. A., Berndt, S., Lee, S. C., Teo, S. H., Thibodeau, S. N., Bojesen, S. E., Gapstur, S. M., Kjaer, S. K., Pejovic, T., Tammela, T. L. J., Dork, T., Bruning, T., Wahlfors, T., Key, T. J., Edwards, T. L., Menon, U., Hamann, U., Mitev, V., Kosma, V. M., Setiawan, V. W., Kristensen, V., Arndt, V., Vogel, W., Zheng, W., Sieh, W., Blot, W. J., Kluzniak, W., Shu, X. O., Gao, Y. T., Schumacher, F., Freedman, M. L., Berchuck, A., Dunning, A. M., Simard, J., Haiman, C. A., Spurdle, A., Sellers, T. A., Hunter, D. J., Henderson, B. E., Kraft, P., Chanock, S. J., Couch, F. J., Hall, P., Gayther, S. A., Easton, D. F., Chenevix-Trench, G., Eeles, R., Pharoah, P. D. P., Lambrechts, D., Investigators, Abctb, Canc, Aocs Study Grp Australian, BioResource, Apcb, Investigators, K. ConFab, Investigators, Nbcs, Network, Genica, Consortium, Practical (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, 6 (9). pp. 1052-1067. ISSN 2159-8274

Full text not available from this repository.

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. (C) 2016 AACR.

Item Type:	Article
Authors (ICR Faculty only):	Orr, Nicholas and Swerdlow, Anthony
All Authors:	Kar, S. P., Beesley, J., Al Olama, A. A., Michailidou, K., Tyrer, J., Kote-Jarai, Z. A., Lawrenson, K., Lindstrom, S., Ramus, S. J., Thompson, D. J., Kibel, A. S., Dansonka-Mieszkowska, A., Michael, A., Dieffenbach, A. K., Gentry-Maharaj, A., Whittemore, A. S., Wolk, A., Monteiro, A., Peixoto, A., Kierzek, A., Cox, A., Rudolph, A., Gonzalez-Neira, A., Wu, A. H., Lindblom, A., Swerdlow, A., Ziogas, A., Ekici, A. B., Burwinkel, B., Karlan, B. Y., Nordestgaard, B. G., Blomqvist, C., Phelan, C., McLean, C., Pearce, C. L., Vachon, C., Cybulski, C., Slavov, C., Stegmaier, C., Maier, C., Ambrosone, C. B., Hogdall, C. K., Teerlink, C. C., Kang, D., Tessier, D. C., Schaid, D. J., Stram, D. O., Cramer, D. W., Neal, D. E., Eccles, D., Flesch-Janys, D., Edwards, D. R. V., Wokozorczyk, D., Levine, D. A., Yannoukakos, D., Sawyer, E. J., Bandera, E. V., Poole, E. M., Goode, E. L., Khusnutdinova, E., Hogdall, E., Song, F. J., Bruinsma, F., Heitz, F., Modugno, F., Hamdy, F. C., Wiklund, F., Giles, G. G., Olsson, H., Wildiers, H., Ulmer, H. U., Pandha, H., Risch, H. A., Darabi, H., Salvesen, H. B., Nevanlinna, H., Gronberg, H., Brenner, H., Brauch, H., Anton-Culver, H., Song, H. L., Lim, H. Y., McNeish, I., Campbell, I., Vergote, I., Gronwald, J., Lubinski, J., Stanford, J. L., Bentez, J., Doherty, J. A., Permuth, J. B., Chang-Claude, J., Donovan, J. L., Dennis, J., Schildkraut, J. M., Schleutker, J., Hopper, J. L., Kupryjanczyk, J., Park, J. Y., Figueroa, J., Clements, J. A., Knight, J. A., Peto, J., Cunningham, J. M., Pow-Sang, J., Batra, J., Czene, K., Lu, K. H., Herkommer, K., Khaw, K. T., Matsuo, K., Muir, K., Offitt, K., Chen, K. X., Moysich, K. B., Aittomaki, K., Odunsi, K., Kiemeney, L. A., Massuger, Lfag, Fitzgerald, L. M., Cook, L. S., Cannon-Albright, L., Hooning, M. J., Pike, M. C., Bolla, M. K., Luedeke, M., Teixeira, M. R., Goodman, M. T., Schmidt, M. K., Riggan, M., Aly, M., Rossing, M. A., Beckmann, M. W., Moisse, M., Sanderson, M., Southey, M. C., Jones, M., Lush, M., Hildebrandt, M. A. T., Hou, M. F., Schoemaker, M. J., Garcia-Closas, M., Bogdanova, N., Rahman, N., Le, N. D., Orr, N., Wentzensen, N., Pashayan, N., Peterlongo, P., Guenel, P., Brennan, P., Paulo, P., Webb, P. M., Broberg, P., Fasching, P. A., Devilee, P., Wang, Q., Cai, Q. Y., Li, Q. Y., Kaneva, R., Butzow, R., Kopperud, R. K., Schmutzler, R. K., Stephenson, R. A., MacInnis, R. J., Hoover, R. N., Winqvist, R., Ness, R., Milne, R. L., Travis, R. C., Benlloch, S., Olson, S. H., McDonnell, S. K., Tworoger, S. S., Maia, S. A., Berndt, S., Lee, S. C., Teo, S. H., Thibodeau, S. N., Bojesen, S. E., Gapstur, S. M., Kjaer, S. K., Pejovic, T., Tammela, T. L. J., Dork, T., Bruning, T., Wahlfors, T., Key, T. J., Edwards, T. L., Menon, U., Hamann, U., Mitev, V., Kosma, V. M., Setiawan, V. W., Kristensen, V., Arndt, V., Vogel, W., Zheng, W., Sieh, W., Blot, W. J., Kluzniak, W., Shu, X. O., Gao, Y. T., Schumacher, F., Freedman, M. L., Berchuck, A., Dunning, A. M., Simard, J., Haiman, C. A., Spurdle, A., Sellers, T. A., Hunter, D. J., Henderson, B. E., Kraft, P., Chanock, S. J., Couch, F. J., Hall, P., Gayther, S. A., Easton, D. F., Chenevix-Trench, G., Eeles, R., Pharoah, P. D. P., Lambrechts, D., Investigators, Abctb, Canc, Aocs Study Grp Australian, BioResource, Apcb, Investigators, K. ConFab, Investigators, Nbcs, Network, Genica, Consortium, Practical
Additional Information:	ISI Document Delivery No.: DW0TT Times Cited: 0 Cited Reference Count: 84 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 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 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 Lubinski, Jan Stanford, Janet L. Bentez, 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, Sofi A. Berndt, Sonja Lee, Soo Chin Teo, Soo-Hwang Thibodeau, Stephen N. Bojesen, Stig E. Gapstur, Susan M. Kjaer, Susanne Krueger Pejovic, Tanja Tammela, Teuvo L. J. Doerk, Thilo Bruening, 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 Dork, Thilo/J-8620-2012 Cancer Research UK [C1287/A12014, C5047/A7357, C5047/A3354, C5047/A10692, C16913/A6135, C490/A6187, C490/A10119, C490/A10124, C536/A13086, C536/A6689, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C8197/A16565]; European Community [223175 (HEALTH-F2-2009-223175)]; NIH [CA128978]; Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; U.S. Department of Defense [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund The Breast Cancer Association Consortium (BCAC), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), and the Ovarian Cancer Association Consortium (OCAC) that contributed breast, prostate, and ovarian cancer data analyzed in this study were in part funded by Cancer Research UK (C1287/A10118 and C1287/A12014 for BCAC; C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, and C16913/A6135 for PRACTICAL; and C490/A6187, C490/A10119, C490/A10124, C536/A13086, and C536/A6689 for OCAC). Funding for the Collaborative Oncological Gene-Environment Study (COGS) infrastructure came from the European Community's Seventh Framework Programme under grant agreement number 223175 (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the NIH (CA128978) and the Post-Cancer GWAS Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112), the U.S. Department of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund [with donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07)]. Additional financial support for contributing studies is documented in the Supplementary Financial Support. 0 AMER ASSOC CANCER RESEARCH PHILADELPHIA CANCER DISCOV
Uncontrolled Keywords:	TRAIL-INDUCED APOPTOSIS PASSENGER COMPLEX CPC BIOLOGICAL PATHWAYS ENRICHMENT ANALYSIS DEATH RECEPTORS RISK LOCI VARIANTS CELLS GENE POPULATION
Research teams:	ICR divisions > Breast Cancer Research > Aetiological Epidemiology ICR divisions > Genetics and Epidemiology > Aetiological Epidemiology ICR divisions > Breast Cancer Research > Complex Trait Genetics
Depositing User:	Barry Jenkins
Date Deposited:	24 Oct 2016 12:40
Last Modified:	24 Oct 2016 12:40
URI:	http://publications.icr.ac.uk/id/eprint/15391

Actions (login required)

View Item