Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
Author(s)
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
Nordstrom, Tobias
Pharoah, Paul
Pashayan, Nora
Schleutker, Johanna
Tammela, Teuvo LJ
Sipeky, Csilla
Auvinen, Anssi
Albanes, Demetrius
Weinstein, Stephanie
Wolk, Alicja
Hakansson, Niclas
West, Catharine ML
Dunning, Alison M
Burnet, Neil
Mucci, Lorelei A
Giovannucci, Edward
Andriole, Gerald L
Cussenot, Olivier
Cancel-Tassin, Geraldine
Koutros, Stella
Freeman, Laura E Beane
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
Gomez-Caamano, Antonio
Szulkin, Robert
Eklund, Martin
Kogevinas, Manolis
Llorca, Javier
Castano-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, Borge G
Nielsen, Sune F
Weischer, Maren
Bisbjerg, Rasmus
Roder, 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 HN
Menegaux, Florence
Truong, Therese
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
Conti, David V
Easton, Douglas F
Wiklund, Fredrik
Chanock, Stephen J
Henderson, Brian E
Kote-Jarai, Zsofia
Haiman, Christopher A
Eeles, Rosalind A
Griffith University Author(s)
Year published
2018
Metadata
Show full item recordAbstract
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 ...
View more >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 PrCa1.
View less >
View more >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 PrCa1.
View less >
Journal Title
Nature Genetics
Volume
50
Subject
Biological sciences
Other biological sciences not elsewhere classified
Biomedical and clinical sciences
Prostate cancer
Genotyped data
European ancestry