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 Kierzek; Angela 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; 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

doi:10.1158/2159-8290.CD-15-1227

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, 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

Producción científica: Article › revisión exhaustiva

140 Citas (Scopus)

Resumen

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.

Idioma original	English (US)
Páginas (desde-hasta)	1052-1067
Número de páginas	16
Publicación	Cancer Discovery
Volumen	6
N.º	9
DOI	https://doi.org/10.1158/2159-8290.CD-15-1227
Estado	Published - sept 1 2016
Publicado de forma externa	Sí

ASJC Scopus subject areas

Oncology

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10.1158/2159-8290.CD-15-1227

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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., ... 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, 6(9), 1052-1067. https://doi.org/10.1158/2159-8290.CD-15-1227

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, 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, n.º 9, pp. 1052-1067. https://doi.org/10.1158/2159-8290.CD-15-1227

@article{3937203827e14c5ca439d562b3ea5409,

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 Lubi{\'n}ski 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 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",

note = "Publisher Copyright: {\textcopyright} 2016 American Association for Cancer Research.",

year = "2016",

month = sep,

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.

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AU - Chenevix-Trench, Georgia

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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

SN - 2159-8274

VL - 6

SP - 1052

EP - 1067

JO - Cancer Discovery

JF - Cancer Discovery

IS - 9

ER -

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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