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Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Schumacher, Fredrick R., Al Olama, Ali Amin, Berndt, Sonja I., Benlloch, Sara, Ahmed, Mahbubl, Saunders, Edward J., Dadaev, Tokhir, Leongamornlert, Daniel, Anokian, Ezequiel, Cieza-Borrella, Clara , Goh, Chee, Brook, Mark N., Sheng, Xin, Fachal, Laura, Dennis, Joe, Tyrer, Jonathan, Muir, Kenneth, Lophatananon, Artitaya, Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Tangen, Catherine M., Goodman, Phyllis J., Thompson, Ian M., Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Nordström, Tobias, Pharoah, Paul, Pashayan, Nora, Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Håkansson, Niclas, West, Catharine M. L., Dunning, Alison M., Burnet, Neil, Mucci, Lorelei A., Giovannucci, Edward, Andriole, Gerald L., Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Beane Freeman, Laura E., Sorensen, Karina Dalsgaard, Orntoft, Torben Falck, Borre, Michael, Maehle, Lovise, Grindedal, Eli Marie, Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Travis, Ruth C., Key, Tim J., Hamilton, Robert J., Fleshner, Neil E., Finelli, Antonio, Ingles, Sue Ann, Stern, Mariana C., Rosenstein, Barry S., Kerns, Sarah L., Ostrer, Harry, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Guo, Xin, Wang, Guomin, Sun, Zan, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., FitzGerald, Liesel M., Kibel, Adam S., Drake, Bettina F., Vega, Ana, Gómez-Caamaño, Antonio, Szulkin, Robert, Eklund, Martin, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Penney, Kathryn L., Stampfer, Meir, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Stanford, Janet L., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Ostrander, Elaine A., Geybels, Milan S., Nordestgaard, Børge G., Nielsen, Sune F., Weischer, Maren, Bisbjerg, Rasmus, Røder, Martin Andreas, Iversen, Peter, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Maier, Christiane, Luedeke, Manuel, Schnoeller, Thomas, Kim, Jeri, Logothetis, Christopher J., John, Esther M., Teixeira, Manuel R., Paulo, Paula, Cardoso, Marta, Neuhausen, Susan L., Steele, Linda, Ding, Yuan Chun, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Lin, Daniel W., Newcomb, Lisa F., Lessel, Davor, Gamulin, Marija, Kulis, Tomislav, Kaneva, Radka, Usmani, Nawaid, Singhal, Sandeep, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Dominguez, Manuela Gago, Castelao, Jose Esteban, Martinez, Maria Elena, Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, Xu, Jianfeng, Khaw, Kay-Tee, Cannon-Albright, Lisa, Pandha, Hardev, Michael, Agnieszka, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Lindstrom, Sara, Turman, Constance, Ma, Jing, Hunter, David J., Riboli, Elio, Siddiq, Afshan, Canzian, Federico, Kolonel, Laurence N., Le Marchand, Loic, Hoover, Robert N., Machiela, Mitchell J., Cui, Zuxi, Kraft, Peter, Amos, Christopher I., Conti, David V., Easton, Douglas F., Wiklund, Fredrik, Chanock, Stephen J., Henderson, Brian E., Kote-Jarai, Zsofia, Haiman, Christopher A. and Eeles, Rosalind A. (2018) Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci Nature Genetics, 50 (7). pp. 928-936.

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Abstract

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P ˂ 5.0 × 10−8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10−9; G˃C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T˃G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Schumacher, Fredrick R.
Al Olama, Ali Amin
Berndt, Sonja I.
Benlloch, Sara
Ahmed, Mahbubl
Saunders, Edward J.
Dadaev, Tokhir
Leongamornlert, Daniel
Anokian, Ezequiel
Cieza-Borrella, Clara
Goh, Chee
Brook, Mark N.
Sheng, Xin
Fachal, Laura
Dennis, Joe
Tyrer, Jonathan
Muir, Kenneth
Lophatananon, Artitaya
Stevens, Victoria L.
Gapstur, Susan M.
Carter, Brian D.
Tangen, Catherine M.
Goodman, Phyllis J.
Thompson, Ian M.
Batra, Jyotsna
Chambers, Suzanne
Moya, Leire
Clements, Judith
Horvath, Lisa
Tilley, Wayne
Risbridger, Gail P.
Gronberg, Henrik
Aly, Markus
Nordström, Tobias
Pharoah, Paul
Pashayan, Nora
Schleutker, Johanna
Tammela, Teuvo L. J.
Sipeky, Csilla
Auvinen, Anssi
Albanes, Demetrius
Weinstein, Stephanie
Wolk, Alicja
Håkansson, Niclas
West, Catharine M. L.
Dunning, Alison M.
Burnet, Neil
Mucci, Lorelei A.
Giovannucci, Edward
Andriole, Gerald L.
Cussenot, Olivier
Cancel-Tassin, Géraldine
Koutros, Stella
Beane Freeman, Laura E.
Sorensen, Karina Dalsgaard
Orntoft, Torben Falck
Borre, Michael
Maehle, Lovise
Grindedal, Eli Marie
Neal, David E.
Donovan, Jenny L.
Hamdy, Freddie C.
Martin, Richard M.
Travis, Ruth C.
Key, Tim J.
Hamilton, Robert J.
Fleshner, Neil E.
Finelli, Antonio
Ingles, Sue Ann
Stern, Mariana C.
Rosenstein, Barry S.
Kerns, Sarah L.
Ostrer, Harry
Lu, Yong-Jie
Zhang, Hong-Wei
Feng, Ninghan
Mao, Xueying
Guo, Xin
Wang, Guomin
Sun, Zan
Giles, Graham G.
Southey, Melissa C.
MacInnis, Robert J.
FitzGerald, Liesel M.
Kibel, Adam S.
Drake, Bettina F.
Vega, Ana
Gómez-Caamaño, Antonio
Szulkin, Robert
Eklund, Martin
Kogevinas, Manolis
Llorca, Javier
Castaño-Vinyals, Gemma
Penney, Kathryn L.
Stampfer, Meir
Park, Jong Y.
Sellers, Thomas A.
Lin, Hui-Yi
Stanford, Janet L.
Cybulski, Cezary
Wokolorczyk, Dominika
Lubinski, Jan
Ostrander, Elaine A.
Geybels, Milan S.
Nordestgaard, Børge G.
Nielsen, Sune F.
Weischer, Maren
Bisbjerg, Rasmus
Røder, Martin Andreas
Iversen, Peter
Brenner, Hermann
Cuk, Katarina
Holleczek, Bernd
Maier, Christiane
Luedeke, Manuel
Schnoeller, Thomas
Kim, Jeri
Logothetis, Christopher J.
John, Esther M.
Teixeira, Manuel R.
Paulo, Paula
Cardoso, Marta
Neuhausen, Susan L.
Steele, Linda
Ding, Yuan Chun
De Ruyck, Kim
De Meerleer, Gert
Ost, Piet
Razack, Azad
Lim, Jasmine
Teo, Soo-Hwang
Lin, Daniel W.
Newcomb, Lisa F.
Lessel, Davor
Gamulin, Marija
Kulis, Tomislav
Kaneva, Radka
Usmani, Nawaid
Singhal, Sandeep
Slavov, Chavdar
Mitev, Vanio
Parliament, Matthew
Claessens, Frank
Joniau, Steven
Van den Broeck, Thomas
Larkin, Samantha
Townsend, Paul A.
Aukim-Hastie, Claire
Dominguez, Manuela Gago
Castelao, Jose Esteban
Martinez, Maria Elena
Roobol, Monique J.
Jenster, Guido
van Schaik, Ron H. N.
Menegaux, Florence
Truong, Thérèse
Koudou, Yves Akoli
Xu, Jianfeng
Khaw, Kay-Tee
Cannon-Albright, Lisa
Pandha, HardevH.Pandha@surrey.ac.uk
Michael, AgnieszkaA.Michael@surrey.ac.uk
Thibodeau, Stephen N.
McDonnell, Shannon K.
Schaid, Daniel J.
Lindstrom, Sara
Turman, Constance
Ma, Jing
Hunter, David J.
Riboli, Elio
Siddiq, Afshan
Canzian, Federico
Kolonel, Laurence N.
Le Marchand, Loic
Hoover, Robert N.
Machiela, Mitchell J.
Cui, Zuxi
Kraft, Peter
Amos, Christopher I.
Conti, David V.
Easton, Douglas F.
Wiklund, Fredrik
Chanock, Stephen J.
Henderson, Brian E.
Kote-Jarai, Zsofia
Haiman, Christopher A.
Eeles, Rosalind A.
Date : 11 June 2018
DOI : 10.1038/s41588-018-0142-8
Copyright Disclaimer : © 2018 Nature America Inc., part of Springer Nature. All rights reserved.
Uncontrolled Keywords : Epidemiology; Genetic association study; Prostate cancer
Depositing User : Clive Harris
Date Deposited : 09 Jul 2018 08:38
Last Modified : 09 Jul 2018 08:38
URI: http://epubs.surrey.ac.uk/id/eprint/848669

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