Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Karoline B. Kuchenbaecker, Susan J. Ramus, Jonathan Tyrer, Andrew Lee, Howard C. Shen, Jonathan Beesley, Kate Lawrenson, Lesley McGuffog, Sue Healey, Janet M. Lee, Tassja J. Spindler, Yvonne G. Lin, Tanja Pejovic, Yukie Bean, Qiyuan Li, Simon Coetzee, Dennis Hazelett, Alexander Miron, Melissa Southey, Mary Beth TerryDavid E. Goldgar, Saundra S. Buys, Ramunas Janavicius, Cecilia M. Dorfling, Elizabeth J. Van Rensburg, Susan L. Neuhausen, Yuan Chun Ding, Thomas V O Hansen, Lars Jønson, Anne Marie Gerdes, Bent Ejlertsen, Daniel Barrowdale, Joe Dennis, Javier Benitez, Ana Osorio, Maria Jose Garcia, Ian Komenaka, Jeffrey N. Weitzel, Pamela Ganschow, Paolo Peterlongo, Loris Bernard, Alessandra Viel, Bernardo Bonanni, Bernard Peissel, Siranoush Manoukian, Paolo Radice, Laura Papi, Laura Ottini, Florentia Fostira, Irene Konstantopoulou, Judy Garber, Debra Frost, Jo Perkins, Radka Platte, Steve Ellis, Andrew K. Godwin, Rita Katharina Schmutzler, Alfons Meindl, Christoph Engel, Christian Sutter, Olga M. Sinilnikova, Francesca Damiola, Sylvie Mazoyer, Dominique Stoppa-Lyonnet, Kathleen Claes, Kim De Leeneer, Judy Kirk, Gustavo C. Rodriguez, Marion Piedmonte, David M. O'Malley, Miguel De La Hoya, Trinidad Caldes, Kristiina Aittomäki, Heli Nevanlinna, J. Collée Margriet, Matti A. Rookus, Jan C. Oosterwijk, Laima Tihomirova, Nadine Tung, Ute Hamann, Claudine Isaccs, Marc Tischkowitz, Evgeny N. Imyanitov, Maria A. Caligo, Ian G. Campbell, Frans B L Hogervorst, Edith Olah, Orland Diez, Ignacio Blanco, Joan Brunet, Conxi Lazaro, Miquel Angel Pujana, Anna Jakubowska, Jacek Gronwald, Jan Lubinski, Grzegorz Sukiennicki, Rosa B. Barkardottir, Marie Plante, Jacques Simard, Penny Soucy, Marco Montagna, Silvia Tognazzo, Manuel R. Teixeira, Vernon S. Pankratz, Xianshu Wang, Noralane Lindor, Csilla I. Szabo, Noah Kauff, Joseph Vijai, Carol A. Aghajanian, Georg Pfeiler, Andreas Berger, Christian F. Singer, Muy Kheng Tea, Catherine M. Phelan, Mark H. Greene, Phuong L. Mai, Gad Rennert, Anna Marie Mulligan, Sandrine Tchatchou, Irene L. Andrulis, Gord Glendon, Amanda Ewart Toland, Uffe Birk Jensen, Torben A. Kruse, Mads Thomassen, Anders Bojesen, Jamal Zidan, Eitan Friedman, Yael Laitman, Maria Soller, Annelie Liljegren, Brita Arver, Zakaria Einbeigi, Marie Stenmark-Askmalm, Olufunmilayo I. Olopade, Robert L. Nussbaum, Timothy R. Rebbeck, Katherine L. Nathanson, Susan M. Domchek, Karen H. Lu, Beth Y. Karlan, Christine Walsh, Jenny Lester, Alexander Hein, Arif B. Ekici, Matthias W. Beckmann, Peter A. Fasching, Diether Lambrechts, Els Van Nieuwenhuysen, Ignace Vergote, Sandrina Lambrechts, Ed Dicks, Jennifer A. Doherty, Kristine G. Wicklund, Mary Anne Rossing, Anja Rudolph, Jenny Chang-Claude, Shan Wang-Gohrke, Ursula Eilber, Kirsten B. Moysich, Kunle Odunsi, Lara Sucheston, Shashi Lele, Lynne R. Wilkens, Marc T. Goodman, Pamela J. Thompson, Yurii B. Shvetsov, Ingo B. Runnebaum, Matthias Dürst, Peter Hillemanns, Thilo Dörk, Natalia Antonenkova, Natalia Bogdanova, Arto Leminen, Liisa M. Pelttari, Ralf Butzow, Francesmary Modugno, Joseph L. Kelley, Robert P. Edwards, Roberta B. Ness, Andreas Du Bois, Florian Heitz, Ira Schwaab, Philipp Harter, Keitaro Matsuo, Satoyo Hosono, Sandra Orsulic, Allan Jensen, Susanne Kruger Kjaer, Estrid Hogdall, Hanis Nazihah Hasmad, Mat Adenan Noor Azmi, Soo Hwang Teo, Yin Ling Woo, Brooke L. Fridley, Ellen L. Goode, Julie M. Cunningham, Robert A. Vierkant, Fiona Bruinsma, Graham G. Giles, Dong Liang, Michelle A T Hildebrandt, Xifeng Wu, Douglas A. Levine, Maria Bisogna, Andrew Berchuck, Edwin S. Iversen, Joellen M. Schildkraut, Patrick Concannon, Rachel Palmieri Weber, Daniel W. Cramer, Kathryn L. Terry, Elizabeth M. Poole, Shelley S. Tworoger, Elisa V. Bandera, Irene Orlow, Sara H. Olson, Camilla Krakstad, Helga B. Salvesen, Ingvild L. Tangen, Line Bjorge, Anne M. Van Altena, Katja K H Aben, Lambertus A. Kiemeney, Leon F A G Massuger, Melissa Kellar, Angela Brooks-Wilson, Linda E. Kelemen, Linda S. Cook, Nhu D. Le, Cezary Cybulski, Hannah Yang, Jolanta Lissowska, Louise A. Brinton, Nicolas Wentzensen, Claus Hogdall, Lene Lundvall, Lotte Nedergaard, Helen Baker, Honglin Song, Diana Eccles, Ian McNeish, James Paul, Karen Carty, Nadeem Siddiqui, Rosalind Glasspool, Alice S. Whittemore, Joseph H. Rothstein, Valerie McGuire, Weiva Sieh, Bu Tian Ji, Wei Zheng, Xiao Ou Shu, Yu Tang Gao, Barry Rosen, Harvey A. Risch, John R. McLaughlin, Steven A. Narod, Alvaro N. Monteiro, Ann Chen, Hui Yi Lin, Jenny Permuth-Wey, Thomas A. Sellers, Ya Yu Tsai, Zhihua Chen, Argyrios Ziogas, Hoda Anton-Culver, Aleksandra Gentry-Maharaj, Usha Menon, Patricia Harrington, Alice W. Lee, Anna H. Wu, Celeste L. Pearce, Gerry Coetzee, Malcolm C. Pike, Agnieszka Dansonka-Mieszkowska, Agnieszka Timorek, Iwona K. Rzepecka, Jolanta Kupryjanczyk, Matt Freedman, Houtan Noushmehr, Douglas F. Easton, Kenneth Offit, Fergus J. Couch, Simon Gayther, Paul P. Pharoah, Antonis C. Antoniou, Georgia Chenevix-Trench

Research output: Contribution to journalArticle

Abstract

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P <5 × 10 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

Original languageEnglish
Pages (from-to)164-171
Number of pages8
JournalNature Genetics
Volume47
Issue number2
DOIs
Publication statusPublished - Jan 1 2015

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Mutation
Genome-Wide Association Study
Ovarian Neoplasms
Meta-Analysis
Ovarian epithelial cancer
Alleles
Genome
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

Kuchenbaecker, K. B., Ramus, S. J., Tyrer, J., Lee, A., Shen, H. C., Beesley, J., ... Chenevix-Trench, G. (2015). Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nature Genetics, 47(2), 164-171. https://doi.org/10.1038/ng.3185

Identification of six new susceptibility loci for invasive epithelial ovarian cancer. / Kuchenbaecker, Karoline B.; Ramus, Susan J.; Tyrer, Jonathan; Lee, Andrew; Shen, Howard C.; Beesley, Jonathan; Lawrenson, Kate; McGuffog, Lesley; Healey, Sue; Lee, Janet M.; Spindler, Tassja J.; Lin, Yvonne G.; Pejovic, Tanja; Bean, Yukie; Li, Qiyuan; Coetzee, Simon; Hazelett, Dennis; Miron, Alexander; Southey, Melissa; Terry, Mary Beth; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Dorfling, Cecilia M.; Van Rensburg, Elizabeth J.; Neuhausen, Susan L.; Ding, Yuan Chun; Hansen, Thomas V O; Jønson, Lars; Gerdes, Anne Marie; Ejlertsen, Bent; Barrowdale, Daniel; Dennis, Joe; Benitez, Javier; Osorio, Ana; Garcia, Maria Jose; Komenaka, Ian; Weitzel, Jeffrey N.; Ganschow, Pamela; Peterlongo, Paolo; Bernard, Loris; Viel, Alessandra; Bonanni, Bernardo; Peissel, Bernard; Manoukian, Siranoush; Radice, Paolo; Papi, Laura; Ottini, Laura; Fostira, Florentia; Konstantopoulou, Irene; Garber, Judy; Frost, Debra; Perkins, Jo; Platte, Radka; Ellis, Steve; Godwin, Andrew K.; Schmutzler, Rita Katharina; Meindl, Alfons; Engel, Christoph; Sutter, Christian; Sinilnikova, Olga M.; Damiola, Francesca; Mazoyer, Sylvie; Stoppa-Lyonnet, Dominique; Claes, Kathleen; De Leeneer, Kim; Kirk, Judy; Rodriguez, Gustavo C.; Piedmonte, Marion; O'Malley, David M.; De La Hoya, Miguel; Caldes, Trinidad; Aittomäki, Kristiina; Nevanlinna, Heli; Margriet, J. Collée; Rookus, Matti A.; Oosterwijk, Jan C.; Tihomirova, Laima; Tung, Nadine; Hamann, Ute; Isaccs, Claudine; Tischkowitz, Marc; Imyanitov, Evgeny N.; Caligo, Maria A.; Campbell, Ian G.; Hogervorst, Frans B L; Olah, Edith; Diez, Orland; Blanco, Ignacio; Brunet, Joan; Lazaro, Conxi; Pujana, Miquel Angel; Jakubowska, Anna; Gronwald, Jacek; Lubinski, Jan; Sukiennicki, Grzegorz; Barkardottir, Rosa B.; Plante, Marie; Simard, Jacques; Soucy, Penny; Montagna, Marco; Tognazzo, Silvia; Teixeira, Manuel R.; Pankratz, Vernon S.; Wang, Xianshu; Lindor, Noralane; Szabo, Csilla I.; Kauff, Noah; Vijai, Joseph; Aghajanian, Carol A.; Pfeiler, Georg; Berger, Andreas; Singer, Christian F.; Tea, Muy Kheng; Phelan, Catherine M.; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Mulligan, Anna Marie; Tchatchou, Sandrine; Andrulis, Irene L.; Glendon, Gord; Toland, Amanda Ewart; Jensen, Uffe Birk; Kruse, Torben A.; Thomassen, Mads; Bojesen, Anders; Zidan, Jamal; Friedman, Eitan; Laitman, Yael; Soller, Maria; Liljegren, Annelie; Arver, Brita; Einbeigi, Zakaria; Stenmark-Askmalm, Marie; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Rebbeck, Timothy R.; Nathanson, Katherine L.; Domchek, Susan M.; Lu, Karen H.; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fasching, Peter A.; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Lambrechts, Sandrina; Dicks, Ed; Doherty, Jennifer A.; Wicklund, Kristine G.; Rossing, Mary Anne; Rudolph, Anja; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Moysich, Kirsten B.; Odunsi, Kunle; Sucheston, Lara; Lele, Shashi; Wilkens, Lynne R.; Goodman, Marc T.; Thompson, Pamela J.; Shvetsov, Yurii B.; Runnebaum, Ingo B.; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Pelttari, Liisa M.; Butzow, Ralf; Modugno, Francesmary; Kelley, Joseph L.; Edwards, Robert P.; Ness, Roberta B.; Du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Matsuo, Keitaro; Hosono, Satoyo; Orsulic, Sandra; Jensen, Allan; Kjaer, Susanne Kruger; Hogdall, Estrid; Hasmad, Hanis Nazihah; Noor Azmi, Mat Adenan; Teo, Soo Hwang; Woo, Yin Ling; Fridley, Brooke L.; Goode, Ellen L.; Cunningham, Julie M.; Vierkant, Robert A.; Bruinsma, Fiona; Giles, Graham G.; Liang, Dong; Hildebrandt, Michelle A T; Wu, Xifeng; Levine, Douglas A.; Bisogna, Maria; Berchuck, Andrew; Iversen, Edwin S.; Schildkraut, Joellen M.; Concannon, Patrick; Weber, Rachel Palmieri; Cramer, Daniel W.; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.; Bandera, Elisa V.; Orlow, Irene; Olson, Sara H.; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.; Bjorge, Line; Van Altena, Anne M.; Aben, Katja K H; Kiemeney, Lambertus A.; Massuger, Leon F A G; Kellar, Melissa; Brooks-Wilson, Angela; Kelemen, Linda E.; Cook, Linda S.; Le, Nhu D.; Cybulski, Cezary; Yang, Hannah; Lissowska, Jolanta; Brinton, Louise A.; Wentzensen, Nicolas; Hogdall, Claus; Lundvall, Lene; Nedergaard, Lotte; Baker, Helen; Song, Honglin; Eccles, Diana; McNeish, Ian; Paul, James; Carty, Karen; Siddiqui, Nadeem; Glasspool, Rosalind; Whittemore, Alice S.; Rothstein, Joseph H.; McGuire, Valerie; Sieh, Weiva; Ji, Bu Tian; Zheng, Wei; Shu, Xiao Ou; Gao, Yu Tang; Rosen, Barry; Risch, Harvey A.; McLaughlin, John R.; Narod, Steven A.; Monteiro, Alvaro N.; Chen, Ann; Lin, Hui Yi; Permuth-Wey, Jenny; Sellers, Thomas A.; Tsai, Ya Yu; Chen, Zhihua; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Harrington, Patricia; Lee, Alice W.; Wu, Anna H.; Pearce, Celeste L.; Coetzee, Gerry; Pike, Malcolm C.; Dansonka-Mieszkowska, Agnieszka; Timorek, Agnieszka; Rzepecka, Iwona K.; Kupryjanczyk, Jolanta; Freedman, Matt; Noushmehr, Houtan; Easton, Douglas F.; Offit, Kenneth; Couch, Fergus J.; Gayther, Simon; Pharoah, Paul P.; Antoniou, Antonis C.; Chenevix-Trench, Georgia.

In: Nature Genetics, Vol. 47, No. 2, 01.01.2015, p. 164-171.

Research output: Contribution to journalArticle

Kuchenbaecker, KB, Ramus, SJ, Tyrer, J, Lee, A, Shen, HC, Beesley, J, Lawrenson, K, McGuffog, L, Healey, S, Lee, JM, Spindler, TJ, Lin, YG, Pejovic, T, Bean, Y, Li, Q, Coetzee, S, Hazelett, D, Miron, A, Southey, M, Terry, MB, Goldgar, DE, Buys, SS, Janavicius, R, Dorfling, CM, Van Rensburg, EJ, Neuhausen, SL, Ding, YC, Hansen, TVO, Jønson, L, Gerdes, AM, Ejlertsen, B, Barrowdale, D, Dennis, J, Benitez, J, Osorio, A, Garcia, MJ, Komenaka, I, Weitzel, JN, Ganschow, P, Peterlongo, P, Bernard, L, Viel, A, Bonanni, B, Peissel, B, Manoukian, S, Radice, P, Papi, L, Ottini, L, Fostira, F, Konstantopoulou, I, Garber, J, Frost, D, Perkins, J, Platte, R, Ellis, S, Godwin, AK, Schmutzler, RK, Meindl, A, Engel, C, Sutter, C, Sinilnikova, OM, Damiola, F, Mazoyer, S, Stoppa-Lyonnet, D, Claes, K, De Leeneer, K, Kirk, J, Rodriguez, GC, Piedmonte, M, O'Malley, DM, De La Hoya, M, Caldes, T, Aittomäki, K, Nevanlinna, H, Margriet, JC, Rookus, MA, Oosterwijk, JC, Tihomirova, L, Tung, N, Hamann, U, Isaccs, C, Tischkowitz, M, Imyanitov, EN, Caligo, MA, Campbell, IG, Hogervorst, FBL, Olah, E, Diez, O, Blanco, I, Brunet, J, Lazaro, C, Pujana, MA, Jakubowska, A, Gronwald, J, Lubinski, J, Sukiennicki, G, Barkardottir, RB, Plante, M, Simard, J, Soucy, P, Montagna, M, Tognazzo, S, Teixeira, MR, Pankratz, VS, Wang, X, Lindor, N, Szabo, CI, Kauff, N, Vijai, J, Aghajanian, CA, Pfeiler, G, Berger, A, Singer, CF, Tea, MK, Phelan, CM, Greene, MH, Mai, PL, Rennert, G, Mulligan, AM, Tchatchou, S, Andrulis, IL, Glendon, G, Toland, AE, Jensen, UB, Kruse, TA, Thomassen, M, Bojesen, A, Zidan, J, Friedman, E, Laitman, Y, Soller, M, Liljegren, A, Arver, B, Einbeigi, Z, Stenmark-Askmalm, M, Olopade, OI, Nussbaum, RL, Rebbeck, TR, Nathanson, KL, Domchek, SM, Lu, KH, Karlan, BY, Walsh, C, Lester, J, Hein, A, Ekici, AB, Beckmann, MW, Fasching, PA, Lambrechts, D, Van Nieuwenhuysen, E, Vergote, I, Lambrechts, S, Dicks, E, Doherty, JA, Wicklund, KG, Rossing, MA, Rudolph, A, Chang-Claude, J, Wang-Gohrke, S, Eilber, U, Moysich, KB, Odunsi, K, Sucheston, L, Lele, S, Wilkens, LR, Goodman, MT, Thompson, PJ, Shvetsov, YB, Runnebaum, IB, Dürst, M, Hillemanns, P, Dörk, T, Antonenkova, N, Bogdanova, N, Leminen, A, Pelttari, LM, Butzow, R, Modugno, F, Kelley, JL, Edwards, RP, Ness, RB, Du Bois, A, Heitz, F, Schwaab, I, Harter, P, Matsuo, K, Hosono, S, Orsulic, S, Jensen, A, Kjaer, SK, Hogdall, E, Hasmad, HN, Noor Azmi, MA, Teo, SH, Woo, YL, Fridley, BL, Goode, EL, Cunningham, JM, Vierkant, RA, Bruinsma, F, Giles, GG, Liang, D, Hildebrandt, MAT, Wu, X, Levine, DA, Bisogna, M, Berchuck, A, Iversen, ES, Schildkraut, JM, Concannon, P, Weber, RP, Cramer, DW, Terry, KL, Poole, EM, Tworoger, SS, Bandera, EV, Orlow, I, Olson, SH, Krakstad, C, Salvesen, HB, Tangen, IL, Bjorge, L, Van Altena, AM, Aben, KKH, Kiemeney, LA, Massuger, LFAG, Kellar, M, Brooks-Wilson, A, Kelemen, LE, Cook, LS, Le, ND, Cybulski, C, Yang, H, Lissowska, J, Brinton, LA, Wentzensen, N, Hogdall, C, Lundvall, L, Nedergaard, L, Baker, H, Song, H, Eccles, D, McNeish, I, Paul, J, Carty, K, Siddiqui, N, Glasspool, R, Whittemore, AS, Rothstein, JH, McGuire, V, Sieh, W, Ji, BT, Zheng, W, Shu, XO, Gao, YT, Rosen, B, Risch, HA, McLaughlin, JR, Narod, SA, Monteiro, AN, Chen, A, Lin, HY, Permuth-Wey, J, Sellers, TA, Tsai, YY, Chen, Z, Ziogas, A, Anton-Culver, H, Gentry-Maharaj, A, Menon, U, Harrington, P, Lee, AW, Wu, AH, Pearce, CL, Coetzee, G, Pike, MC, Dansonka-Mieszkowska, A, Timorek, A, Rzepecka, IK, Kupryjanczyk, J, Freedman, M, Noushmehr, H, Easton, DF, Offit, K, Couch, FJ, Gayther, S, Pharoah, PP, Antoniou, AC & Chenevix-Trench, G 2015, 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer', Nature Genetics, vol. 47, no. 2, pp. 164-171. https://doi.org/10.1038/ng.3185
Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J et al. Identification of six new susceptibility loci for invasive epithelial ovarian cancer. Nature Genetics. 2015 Jan 1;47(2):164-171. https://doi.org/10.1038/ng.3185
Kuchenbaecker, Karoline B. ; Ramus, Susan J. ; Tyrer, Jonathan ; Lee, Andrew ; Shen, Howard C. ; Beesley, Jonathan ; Lawrenson, Kate ; McGuffog, Lesley ; Healey, Sue ; Lee, Janet M. ; Spindler, Tassja J. ; Lin, Yvonne G. ; Pejovic, Tanja ; Bean, Yukie ; Li, Qiyuan ; Coetzee, Simon ; Hazelett, Dennis ; Miron, Alexander ; Southey, Melissa ; Terry, Mary Beth ; Goldgar, David E. ; Buys, Saundra S. ; Janavicius, Ramunas ; Dorfling, Cecilia M. ; Van Rensburg, Elizabeth J. ; Neuhausen, Susan L. ; Ding, Yuan Chun ; Hansen, Thomas V O ; Jønson, Lars ; Gerdes, Anne Marie ; Ejlertsen, Bent ; Barrowdale, Daniel ; Dennis, Joe ; Benitez, Javier ; Osorio, Ana ; Garcia, Maria Jose ; Komenaka, Ian ; Weitzel, Jeffrey N. ; Ganschow, Pamela ; Peterlongo, Paolo ; Bernard, Loris ; Viel, Alessandra ; Bonanni, Bernardo ; Peissel, Bernard ; Manoukian, Siranoush ; Radice, Paolo ; Papi, Laura ; Ottini, Laura ; Fostira, Florentia ; Konstantopoulou, Irene ; Garber, Judy ; Frost, Debra ; Perkins, Jo ; Platte, Radka ; Ellis, Steve ; Godwin, Andrew K. ; Schmutzler, Rita Katharina ; Meindl, Alfons ; Engel, Christoph ; Sutter, Christian ; Sinilnikova, Olga M. ; Damiola, Francesca ; Mazoyer, Sylvie ; Stoppa-Lyonnet, Dominique ; Claes, Kathleen ; De Leeneer, Kim ; Kirk, Judy ; Rodriguez, Gustavo C. ; Piedmonte, Marion ; O'Malley, David M. ; De La Hoya, Miguel ; Caldes, Trinidad ; Aittomäki, Kristiina ; Nevanlinna, Heli ; Margriet, J. Collée ; Rookus, Matti A. ; Oosterwijk, Jan C. ; Tihomirova, Laima ; Tung, Nadine ; Hamann, Ute ; Isaccs, Claudine ; Tischkowitz, Marc ; Imyanitov, Evgeny N. ; Caligo, Maria A. ; Campbell, Ian G. ; Hogervorst, Frans B L ; Olah, Edith ; Diez, Orland ; Blanco, Ignacio ; Brunet, Joan ; Lazaro, Conxi ; Pujana, Miquel Angel ; Jakubowska, Anna ; Gronwald, Jacek ; Lubinski, Jan ; Sukiennicki, Grzegorz ; Barkardottir, Rosa B. ; Plante, Marie ; Simard, Jacques ; Soucy, Penny ; Montagna, Marco ; Tognazzo, Silvia ; Teixeira, Manuel R. ; Pankratz, Vernon S. ; Wang, Xianshu ; Lindor, Noralane ; Szabo, Csilla I. ; Kauff, Noah ; Vijai, Joseph ; Aghajanian, Carol A. ; Pfeiler, Georg ; Berger, Andreas ; Singer, Christian F. ; Tea, Muy Kheng ; Phelan, Catherine M. ; Greene, Mark H. ; Mai, Phuong L. ; Rennert, Gad ; Mulligan, Anna Marie ; Tchatchou, Sandrine ; Andrulis, Irene L. ; Glendon, Gord ; Toland, Amanda Ewart ; Jensen, Uffe Birk ; Kruse, Torben A. ; Thomassen, Mads ; Bojesen, Anders ; Zidan, Jamal ; Friedman, Eitan ; Laitman, Yael ; Soller, Maria ; Liljegren, Annelie ; Arver, Brita ; Einbeigi, Zakaria ; Stenmark-Askmalm, Marie ; Olopade, Olufunmilayo I. ; Nussbaum, Robert L. ; Rebbeck, Timothy R. ; Nathanson, Katherine L. ; Domchek, Susan M. ; Lu, Karen H. ; Karlan, Beth Y. ; Walsh, Christine ; Lester, Jenny ; Hein, Alexander ; Ekici, Arif B. ; Beckmann, Matthias W. ; Fasching, Peter A. ; Lambrechts, Diether ; Van Nieuwenhuysen, Els ; Vergote, Ignace ; Lambrechts, Sandrina ; Dicks, Ed ; Doherty, Jennifer A. ; Wicklund, Kristine G. ; Rossing, Mary Anne ; Rudolph, Anja ; Chang-Claude, Jenny ; Wang-Gohrke, Shan ; Eilber, Ursula ; Moysich, Kirsten B. ; Odunsi, Kunle ; Sucheston, Lara ; Lele, Shashi ; Wilkens, Lynne R. ; Goodman, Marc T. ; Thompson, Pamela J. ; Shvetsov, Yurii B. ; Runnebaum, Ingo B. ; Dürst, Matthias ; Hillemanns, Peter ; Dörk, Thilo ; Antonenkova, Natalia ; Bogdanova, Natalia ; Leminen, Arto ; Pelttari, Liisa M. ; Butzow, Ralf ; Modugno, Francesmary ; Kelley, Joseph L. ; Edwards, Robert P. ; Ness, Roberta B. ; Du Bois, Andreas ; Heitz, Florian ; Schwaab, Ira ; Harter, Philipp ; Matsuo, Keitaro ; Hosono, Satoyo ; Orsulic, Sandra ; Jensen, Allan ; Kjaer, Susanne Kruger ; Hogdall, Estrid ; Hasmad, Hanis Nazihah ; Noor Azmi, Mat Adenan ; Teo, Soo Hwang ; Woo, Yin Ling ; Fridley, Brooke L. ; Goode, Ellen L. ; Cunningham, Julie M. ; Vierkant, Robert A. ; Bruinsma, Fiona ; Giles, Graham G. ; Liang, Dong ; Hildebrandt, Michelle A T ; Wu, Xifeng ; Levine, Douglas A. ; Bisogna, Maria ; Berchuck, Andrew ; Iversen, Edwin S. ; Schildkraut, Joellen M. ; Concannon, Patrick ; Weber, Rachel Palmieri ; Cramer, Daniel W. ; Terry, Kathryn L. ; Poole, Elizabeth M. ; Tworoger, Shelley S. ; Bandera, Elisa V. ; Orlow, Irene ; Olson, Sara H. ; Krakstad, Camilla ; Salvesen, Helga B. ; Tangen, Ingvild L. ; Bjorge, Line ; Van Altena, Anne M. ; Aben, Katja K H ; Kiemeney, Lambertus A. ; Massuger, Leon F A G ; Kellar, Melissa ; Brooks-Wilson, Angela ; Kelemen, Linda E. ; Cook, Linda S. ; Le, Nhu D. ; Cybulski, Cezary ; Yang, Hannah ; Lissowska, Jolanta ; Brinton, Louise A. ; Wentzensen, Nicolas ; Hogdall, Claus ; Lundvall, Lene ; Nedergaard, Lotte ; Baker, Helen ; Song, Honglin ; Eccles, Diana ; McNeish, Ian ; Paul, James ; Carty, Karen ; Siddiqui, Nadeem ; Glasspool, Rosalind ; Whittemore, Alice S. ; Rothstein, Joseph H. ; McGuire, Valerie ; Sieh, Weiva ; Ji, Bu Tian ; Zheng, Wei ; Shu, Xiao Ou ; Gao, Yu Tang ; Rosen, Barry ; Risch, Harvey A. ; McLaughlin, John R. ; Narod, Steven A. ; Monteiro, Alvaro N. ; Chen, Ann ; Lin, Hui Yi ; Permuth-Wey, Jenny ; Sellers, Thomas A. ; Tsai, Ya Yu ; Chen, Zhihua ; Ziogas, Argyrios ; Anton-Culver, Hoda ; Gentry-Maharaj, Aleksandra ; Menon, Usha ; Harrington, Patricia ; Lee, Alice W. ; Wu, Anna H. ; Pearce, Celeste L. ; Coetzee, Gerry ; Pike, Malcolm C. ; Dansonka-Mieszkowska, Agnieszka ; Timorek, Agnieszka ; Rzepecka, Iwona K. ; Kupryjanczyk, Jolanta ; Freedman, Matt ; Noushmehr, Houtan ; Easton, Douglas F. ; Offit, Kenneth ; Couch, Fergus J. ; Gayther, Simon ; Pharoah, Paul P. ; Antoniou, Antonis C. ; Chenevix-Trench, Georgia. / Identification of six new susceptibility loci for invasive epithelial ovarian cancer. In: Nature Genetics. 2015 ; Vol. 47, No. 2. pp. 164-171.
@article{94d45c87b8214da4807ed48ff4e8b3cb,
title = "Identification of six new susceptibility loci for invasive epithelial ovarian cancer",
abstract = "Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P <5 × 10 {\^a}+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.",
author = "Kuchenbaecker, {Karoline B.} and Ramus, {Susan J.} and Jonathan Tyrer and Andrew Lee and Shen, {Howard C.} and Jonathan Beesley and Kate Lawrenson and Lesley McGuffog and Sue Healey and Lee, {Janet M.} and Spindler, {Tassja J.} and Lin, {Yvonne G.} and Tanja Pejovic and Yukie Bean and Qiyuan Li and Simon Coetzee and Dennis Hazelett and Alexander Miron and Melissa Southey and Terry, {Mary Beth} and Goldgar, {David E.} and Buys, {Saundra S.} and Ramunas Janavicius and Dorfling, {Cecilia M.} and {Van Rensburg}, {Elizabeth J.} and Neuhausen, {Susan L.} and Ding, {Yuan Chun} and Hansen, {Thomas V O} and Lars J{\o}nson and Gerdes, {Anne Marie} and Bent Ejlertsen and Daniel Barrowdale and Joe Dennis and Javier Benitez and Ana Osorio and Garcia, {Maria Jose} and Ian Komenaka and Weitzel, {Jeffrey N.} and Pamela Ganschow and Paolo Peterlongo and Loris Bernard and Alessandra Viel and Bernardo Bonanni and Bernard Peissel and Siranoush Manoukian and Paolo Radice and Laura Papi and Laura Ottini and Florentia Fostira and Irene Konstantopoulou and Judy Garber and Debra Frost and Jo Perkins and Radka Platte and Steve Ellis and Godwin, {Andrew K.} and Schmutzler, {Rita Katharina} and Alfons Meindl and Christoph Engel and Christian Sutter and Sinilnikova, {Olga M.} and Francesca Damiola and Sylvie Mazoyer and Dominique Stoppa-Lyonnet and Kathleen Claes and {De Leeneer}, Kim and Judy Kirk and Rodriguez, {Gustavo C.} and Marion Piedmonte and O'Malley, {David M.} and {De La Hoya}, Miguel and Trinidad Caldes and Kristiina Aittom{\"a}ki and Heli Nevanlinna and Margriet, {J. Coll{\'e}e} and Rookus, {Matti A.} and Oosterwijk, {Jan C.} and Laima Tihomirova and Nadine Tung and Ute Hamann and Claudine Isaccs and Marc Tischkowitz and Imyanitov, {Evgeny N.} and Caligo, {Maria A.} and Campbell, {Ian G.} and Hogervorst, {Frans B L} and Edith Olah and Orland Diez and Ignacio Blanco and Joan Brunet and Conxi Lazaro and Pujana, {Miquel Angel} and Anna Jakubowska and Jacek Gronwald and Jan Lubinski and Grzegorz Sukiennicki and Barkardottir, {Rosa B.} and Marie Plante and Jacques Simard and Penny Soucy and Marco Montagna and Silvia Tognazzo and Teixeira, {Manuel R.} and Pankratz, {Vernon S.} and Xianshu Wang and Noralane Lindor and Szabo, {Csilla I.} and Noah Kauff and Joseph Vijai and Aghajanian, {Carol A.} and Georg Pfeiler and Andreas Berger and Singer, {Christian F.} and Tea, {Muy Kheng} and Phelan, {Catherine M.} and Greene, {Mark H.} and Mai, {Phuong L.} and Gad Rennert and Mulligan, {Anna Marie} and Sandrine Tchatchou and Andrulis, {Irene L.} and Gord Glendon and Toland, {Amanda Ewart} and Jensen, {Uffe Birk} and Kruse, {Torben A.} and Mads Thomassen and Anders Bojesen and Jamal Zidan and Eitan Friedman and Yael Laitman and Maria Soller and Annelie Liljegren and Brita Arver and Zakaria Einbeigi and Marie Stenmark-Askmalm and Olopade, {Olufunmilayo I.} and Nussbaum, {Robert L.} and Rebbeck, {Timothy R.} and Nathanson, {Katherine L.} and Domchek, {Susan M.} and Lu, {Karen H.} and Karlan, {Beth Y.} and Christine Walsh and Jenny Lester and Alexander Hein and Ekici, {Arif B.} and Beckmann, {Matthias W.} and Fasching, {Peter A.} and Diether Lambrechts and {Van Nieuwenhuysen}, Els and Ignace Vergote and Sandrina Lambrechts and Ed Dicks and Doherty, {Jennifer A.} and Wicklund, {Kristine G.} and Rossing, {Mary Anne} and Anja Rudolph and Jenny Chang-Claude and Shan Wang-Gohrke and Ursula Eilber and Moysich, {Kirsten B.} and Kunle Odunsi and Lara Sucheston and Shashi Lele and Wilkens, {Lynne R.} and Goodman, {Marc T.} and Thompson, {Pamela J.} and Shvetsov, {Yurii B.} and Runnebaum, {Ingo B.} and Matthias D{\"u}rst and Peter Hillemanns and Thilo D{\"o}rk and Natalia Antonenkova and Natalia Bogdanova and Arto Leminen and Pelttari, {Liisa M.} and Ralf Butzow and Francesmary Modugno and Kelley, {Joseph L.} and Edwards, {Robert P.} and Ness, {Roberta B.} and {Du Bois}, Andreas and Florian Heitz and Ira Schwaab and Philipp Harter and Keitaro Matsuo and Satoyo Hosono and Sandra Orsulic and Allan Jensen and Kjaer, {Susanne Kruger} and Estrid Hogdall and Hasmad, {Hanis Nazihah} and {Noor Azmi}, {Mat Adenan} and Teo, {Soo Hwang} and Woo, {Yin Ling} and Fridley, {Brooke L.} and Goode, {Ellen L.} and Cunningham, {Julie M.} and Vierkant, {Robert A.} and Fiona Bruinsma and Giles, {Graham G.} and Dong Liang and Hildebrandt, {Michelle A T} and Xifeng Wu and Levine, {Douglas A.} and Maria Bisogna and Andrew Berchuck and Iversen, {Edwin S.} and Schildkraut, {Joellen M.} and Patrick Concannon and Weber, {Rachel Palmieri} and Cramer, {Daniel W.} and Terry, {Kathryn L.} and Poole, {Elizabeth M.} and Tworoger, {Shelley S.} and Bandera, {Elisa V.} and Irene Orlow and Olson, {Sara H.} and Camilla Krakstad and Salvesen, {Helga B.} and Tangen, {Ingvild L.} and Line Bjorge and {Van Altena}, {Anne M.} and Aben, {Katja K H} and Kiemeney, {Lambertus A.} and Massuger, {Leon F A G} and Melissa Kellar and Angela Brooks-Wilson and Kelemen, {Linda E.} and Cook, {Linda S.} and Le, {Nhu D.} and Cezary Cybulski and Hannah Yang and Jolanta Lissowska and Brinton, {Louise A.} and Nicolas Wentzensen and Claus Hogdall and Lene Lundvall and Lotte Nedergaard and Helen Baker and Honglin Song and Diana Eccles and Ian McNeish and James Paul and Karen Carty and Nadeem Siddiqui and Rosalind Glasspool and Whittemore, {Alice S.} and Rothstein, {Joseph H.} and Valerie McGuire and Weiva Sieh and Ji, {Bu Tian} and Wei Zheng and Shu, {Xiao Ou} and Gao, {Yu Tang} and Barry Rosen and Risch, {Harvey A.} and McLaughlin, {John R.} and Narod, {Steven A.} and Monteiro, {Alvaro N.} and Ann Chen and Lin, {Hui Yi} and Jenny Permuth-Wey and Sellers, {Thomas A.} and Tsai, {Ya Yu} and Zhihua Chen and Argyrios Ziogas and Hoda Anton-Culver and Aleksandra Gentry-Maharaj and Usha Menon and Patricia Harrington and Lee, {Alice W.} and Wu, {Anna H.} and Pearce, {Celeste L.} and Gerry Coetzee and Pike, {Malcolm C.} and Agnieszka Dansonka-Mieszkowska and Agnieszka Timorek and Rzepecka, {Iwona K.} and Jolanta Kupryjanczyk and Matt Freedman and Houtan Noushmehr and Easton, {Douglas F.} and Kenneth Offit and Couch, {Fergus J.} and Simon Gayther and Pharoah, {Paul P.} and Antoniou, {Antonis C.} and Georgia Chenevix-Trench",
year = "2015",
month = "1",
day = "1",
doi = "10.1038/ng.3185",
language = "English",
volume = "47",
pages = "164--171",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Identification of six new susceptibility loci for invasive epithelial ovarian cancer

AU - Kuchenbaecker, Karoline B.

AU - Ramus, Susan J.

AU - Tyrer, Jonathan

AU - Lee, Andrew

AU - Shen, Howard C.

AU - Beesley, Jonathan

AU - Lawrenson, Kate

AU - McGuffog, Lesley

AU - Healey, Sue

AU - Lee, Janet M.

AU - Spindler, Tassja J.

AU - Lin, Yvonne G.

AU - Pejovic, Tanja

AU - Bean, Yukie

AU - Li, Qiyuan

AU - Coetzee, Simon

AU - Hazelett, Dennis

AU - Miron, Alexander

AU - Southey, Melissa

AU - Terry, Mary Beth

AU - Goldgar, David E.

AU - Buys, Saundra S.

AU - Janavicius, Ramunas

AU - Dorfling, Cecilia M.

AU - Van Rensburg, Elizabeth J.

AU - Neuhausen, Susan L.

AU - Ding, Yuan Chun

AU - Hansen, Thomas V O

AU - Jønson, Lars

AU - Gerdes, Anne Marie

AU - Ejlertsen, Bent

AU - Barrowdale, Daniel

AU - Dennis, Joe

AU - Benitez, Javier

AU - Osorio, Ana

AU - Garcia, Maria Jose

AU - Komenaka, Ian

AU - Weitzel, Jeffrey N.

AU - Ganschow, Pamela

AU - Peterlongo, Paolo

AU - Bernard, Loris

AU - Viel, Alessandra

AU - Bonanni, Bernardo

AU - Peissel, Bernard

AU - Manoukian, Siranoush

AU - Radice, Paolo

AU - Papi, Laura

AU - Ottini, Laura

AU - Fostira, Florentia

AU - Konstantopoulou, Irene

AU - Garber, Judy

AU - Frost, Debra

AU - Perkins, Jo

AU - Platte, Radka

AU - Ellis, Steve

AU - Godwin, Andrew K.

AU - Schmutzler, Rita Katharina

AU - Meindl, Alfons

AU - Engel, Christoph

AU - Sutter, Christian

AU - Sinilnikova, Olga M.

AU - Damiola, Francesca

AU - Mazoyer, Sylvie

AU - Stoppa-Lyonnet, Dominique

AU - Claes, Kathleen

AU - De Leeneer, Kim

AU - Kirk, Judy

AU - Rodriguez, Gustavo C.

AU - Piedmonte, Marion

AU - O'Malley, David M.

AU - De La Hoya, Miguel

AU - Caldes, Trinidad

AU - Aittomäki, Kristiina

AU - Nevanlinna, Heli

AU - Margriet, J. Collée

AU - Rookus, Matti A.

AU - Oosterwijk, Jan C.

AU - Tihomirova, Laima

AU - Tung, Nadine

AU - Hamann, Ute

AU - Isaccs, Claudine

AU - Tischkowitz, Marc

AU - Imyanitov, Evgeny N.

AU - Caligo, Maria A.

AU - Campbell, Ian G.

AU - Hogervorst, Frans B L

AU - Olah, Edith

AU - Diez, Orland

AU - Blanco, Ignacio

AU - Brunet, Joan

AU - Lazaro, Conxi

AU - Pujana, Miquel Angel

AU - Jakubowska, Anna

AU - Gronwald, Jacek

AU - Lubinski, Jan

AU - Sukiennicki, Grzegorz

AU - Barkardottir, Rosa B.

AU - Plante, Marie

AU - Simard, Jacques

AU - Soucy, Penny

AU - Montagna, Marco

AU - Tognazzo, Silvia

AU - Teixeira, Manuel R.

AU - Pankratz, Vernon S.

AU - Wang, Xianshu

AU - Lindor, Noralane

AU - Szabo, Csilla I.

AU - Kauff, Noah

AU - Vijai, Joseph

AU - Aghajanian, Carol A.

AU - Pfeiler, Georg

AU - Berger, Andreas

AU - Singer, Christian F.

AU - Tea, Muy Kheng

AU - Phelan, Catherine M.

AU - Greene, Mark H.

AU - Mai, Phuong L.

AU - Rennert, Gad

AU - Mulligan, Anna Marie

AU - Tchatchou, Sandrine

AU - Andrulis, Irene L.

AU - Glendon, Gord

AU - Toland, Amanda Ewart

AU - Jensen, Uffe Birk

AU - Kruse, Torben A.

AU - Thomassen, Mads

AU - Bojesen, Anders

AU - Zidan, Jamal

AU - Friedman, Eitan

AU - Laitman, Yael

AU - Soller, Maria

AU - Liljegren, Annelie

AU - Arver, Brita

AU - Einbeigi, Zakaria

AU - Stenmark-Askmalm, Marie

AU - Olopade, Olufunmilayo I.

AU - Nussbaum, Robert L.

AU - Rebbeck, Timothy R.

AU - Nathanson, Katherine L.

AU - Domchek, Susan M.

AU - Lu, Karen H.

AU - Karlan, Beth Y.

AU - Walsh, Christine

AU - Lester, Jenny

AU - Hein, Alexander

AU - Ekici, Arif B.

AU - Beckmann, Matthias W.

AU - Fasching, Peter A.

AU - Lambrechts, Diether

AU - Van Nieuwenhuysen, Els

AU - Vergote, Ignace

AU - Lambrechts, Sandrina

AU - Dicks, Ed

AU - Doherty, Jennifer A.

AU - Wicklund, Kristine G.

AU - Rossing, Mary Anne

AU - Rudolph, Anja

AU - Chang-Claude, Jenny

AU - Wang-Gohrke, Shan

AU - Eilber, Ursula

AU - Moysich, Kirsten B.

AU - Odunsi, Kunle

AU - Sucheston, Lara

AU - Lele, Shashi

AU - Wilkens, Lynne R.

AU - Goodman, Marc T.

AU - Thompson, Pamela J.

AU - Shvetsov, Yurii B.

AU - Runnebaum, Ingo B.

AU - Dürst, Matthias

AU - Hillemanns, Peter

AU - Dörk, Thilo

AU - Antonenkova, Natalia

AU - Bogdanova, Natalia

AU - Leminen, Arto

AU - Pelttari, Liisa M.

AU - Butzow, Ralf

AU - Modugno, Francesmary

AU - Kelley, Joseph L.

AU - Edwards, Robert P.

AU - Ness, Roberta B.

AU - Du Bois, Andreas

AU - Heitz, Florian

AU - Schwaab, Ira

AU - Harter, Philipp

AU - Matsuo, Keitaro

AU - Hosono, Satoyo

AU - Orsulic, Sandra

AU - Jensen, Allan

AU - Kjaer, Susanne Kruger

AU - Hogdall, Estrid

AU - Hasmad, Hanis Nazihah

AU - Noor Azmi, Mat Adenan

AU - Teo, Soo Hwang

AU - Woo, Yin Ling

AU - Fridley, Brooke L.

AU - Goode, Ellen L.

AU - Cunningham, Julie M.

AU - Vierkant, Robert A.

AU - Bruinsma, Fiona

AU - Giles, Graham G.

AU - Liang, Dong

AU - Hildebrandt, Michelle A T

AU - Wu, Xifeng

AU - Levine, Douglas A.

AU - Bisogna, Maria

AU - Berchuck, Andrew

AU - Iversen, Edwin S.

AU - Schildkraut, Joellen M.

AU - Concannon, Patrick

AU - Weber, Rachel Palmieri

AU - Cramer, Daniel W.

AU - Terry, Kathryn L.

AU - Poole, Elizabeth M.

AU - Tworoger, Shelley S.

AU - Bandera, Elisa V.

AU - Orlow, Irene

AU - Olson, Sara H.

AU - Krakstad, Camilla

AU - Salvesen, Helga B.

AU - Tangen, Ingvild L.

AU - Bjorge, Line

AU - Van Altena, Anne M.

AU - Aben, Katja K H

AU - Kiemeney, Lambertus A.

AU - Massuger, Leon F A G

AU - Kellar, Melissa

AU - Brooks-Wilson, Angela

AU - Kelemen, Linda E.

AU - Cook, Linda S.

AU - Le, Nhu D.

AU - Cybulski, Cezary

AU - Yang, Hannah

AU - Lissowska, Jolanta

AU - Brinton, Louise A.

AU - Wentzensen, Nicolas

AU - Hogdall, Claus

AU - Lundvall, Lene

AU - Nedergaard, Lotte

AU - Baker, Helen

AU - Song, Honglin

AU - Eccles, Diana

AU - McNeish, Ian

AU - Paul, James

AU - Carty, Karen

AU - Siddiqui, Nadeem

AU - Glasspool, Rosalind

AU - Whittemore, Alice S.

AU - Rothstein, Joseph H.

AU - McGuire, Valerie

AU - Sieh, Weiva

AU - Ji, Bu Tian

AU - Zheng, Wei

AU - Shu, Xiao Ou

AU - Gao, Yu Tang

AU - Rosen, Barry

AU - Risch, Harvey A.

AU - McLaughlin, John R.

AU - Narod, Steven A.

AU - Monteiro, Alvaro N.

AU - Chen, Ann

AU - Lin, Hui Yi

AU - Permuth-Wey, Jenny

AU - Sellers, Thomas A.

AU - Tsai, Ya Yu

AU - Chen, Zhihua

AU - Ziogas, Argyrios

AU - Anton-Culver, Hoda

AU - Gentry-Maharaj, Aleksandra

AU - Menon, Usha

AU - Harrington, Patricia

AU - Lee, Alice W.

AU - Wu, Anna H.

AU - Pearce, Celeste L.

AU - Coetzee, Gerry

AU - Pike, Malcolm C.

AU - Dansonka-Mieszkowska, Agnieszka

AU - Timorek, Agnieszka

AU - Rzepecka, Iwona K.

AU - Kupryjanczyk, Jolanta

AU - Freedman, Matt

AU - Noushmehr, Houtan

AU - Easton, Douglas F.

AU - Offit, Kenneth

AU - Couch, Fergus J.

AU - Gayther, Simon

AU - Pharoah, Paul P.

AU - Antoniou, Antonis C.

AU - Chenevix-Trench, Georgia

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P <5 × 10 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

AB - Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P <5 × 10 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

UR - http://www.scopus.com/inward/record.url?scp=84929171835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929171835&partnerID=8YFLogxK

U2 - 10.1038/ng.3185

DO - 10.1038/ng.3185

M3 - Article

AN - SCOPUS:84929171835

VL - 47

SP - 164

EP - 171

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 2

ER -