Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
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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; Eeles, Rosalind A; Profile Study; Australian Prostate Cancer BioResource (APCB); IMPACT Study; Canary PASS Investigators; Breast and Prostate Cancer Cohort Consortium (BPC3); PRACTICAL Consortium; Cancer of the Prostate in Sweden (CAPS); Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS); Genetic Associations and Mechanisms in Oncology Consortium (GAME-ON); Elucidating Loci Involved in Prostate Cancer Susceptibility Consortium (ELLIPSE).
in: NAT GENET, Jahrgang 50, Nr. 7, 07.2018, S. 928-936.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › Andere (Vorworte u.ä.) › Forschung
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TY - JOUR
T1 - Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
AU - Schumacher, Fredrick R
AU - Al Olama, Ali Amin
AU - Berndt, Sonja I
AU - Benlloch, Sara
AU - Ahmed, Mahbubl
AU - Saunders, Edward J
AU - Dadaev, Tokhir
AU - Leongamornlert, Daniel
AU - Anokian, Ezequiel
AU - Cieza-Borrella, Clara
AU - Goh, Chee
AU - Brook, Mark N
AU - Sheng, Xin
AU - Fachal, Laura
AU - Dennis, Joe
AU - Tyrer, Jonathan
AU - Muir, Kenneth
AU - Lophatananon, Artitaya
AU - Stevens, Victoria L
AU - Gapstur, Susan M
AU - Carter, Brian D
AU - Tangen, Catherine M
AU - Goodman, Phyllis J
AU - Thompson, Ian M
AU - Batra, Jyotsna
AU - Chambers, Suzanne
AU - Moya, Leire
AU - Clements, Judith
AU - Horvath, Lisa
AU - Tilley, Wayne
AU - Risbridger, Gail P
AU - Gronberg, Henrik
AU - Aly, Markus
AU - Nordström, Tobias
AU - Pharoah, Paul
AU - Pashayan, Nora
AU - Schleutker, Johanna
AU - Tammela, Teuvo L J
AU - Sipeky, Csilla
AU - Auvinen, Anssi
AU - Albanes, Demetrius
AU - Weinstein, Stephanie
AU - Wolk, Alicja
AU - Håkansson, Niclas
AU - West, Catharine M L
AU - Dunning, Alison M
AU - Burnet, Neil
AU - Mucci, Lorelei A
AU - Giovannucci, Edward
AU - Andriole, Gerald L
AU - Cussenot, Olivier
AU - Cancel-Tassin, Géraldine
AU - Koutros, Stella
AU - Beane Freeman, Laura E
AU - Sorensen, Karina Dalsgaard
AU - Orntoft, Torben Falck
AU - Borre, Michael
AU - Maehle, Lovise
AU - Grindedal, Eli Marie
AU - Neal, David E
AU - Donovan, Jenny L
AU - Hamdy, Freddie C
AU - Martin, Richard M
AU - Travis, Ruth C
AU - Key, Tim J
AU - Hamilton, Robert J
AU - Fleshner, Neil E
AU - Finelli, Antonio
AU - Ingles, Sue Ann
AU - Stern, Mariana C
AU - Rosenstein, Barry S
AU - Kerns, Sarah L
AU - Ostrer, Harry
AU - Lu, Yong-Jie
AU - Zhang, Hong-Wei
AU - Feng, Ninghan
AU - Mao, Xueying
AU - Guo, Xin
AU - Wang, Guomin
AU - Sun, Zan
AU - Giles, Graham G
AU - Southey, Melissa C
AU - MacInnis, Robert J
AU - FitzGerald, Liesel M
AU - Kibel, Adam S
AU - Drake, Bettina F
AU - Vega, Ana
AU - Gómez-Caamaño, Antonio
AU - Szulkin, Robert
AU - Eklund, Martin
AU - Kogevinas, Manolis
AU - Llorca, Javier
AU - Castaño-Vinyals, Gemma
AU - Penney, Kathryn L
AU - Stampfer, Meir
AU - Park, Jong Y
AU - Sellers, Thomas A
AU - Lin, Hui-Yi
AU - Stanford, Janet L
AU - Cybulski, Cezary
AU - Wokolorczyk, Dominika
AU - Lubinski, Jan
AU - Ostrander, Elaine A
AU - Geybels, Milan S
AU - Nordestgaard, Børge G
AU - Nielsen, Sune F
AU - Weischer, Maren
AU - Bisbjerg, Rasmus
AU - Røder, Martin Andreas
AU - Iversen, Peter
AU - Brenner, Hermann
AU - Cuk, Katarina
AU - Holleczek, Bernd
AU - Maier, Christiane
AU - Luedeke, Manuel
AU - Schnoeller, Thomas
AU - Kim, Jeri
AU - Logothetis, Christopher J
AU - John, Esther M
AU - Teixeira, Manuel R
AU - Paulo, Paula
AU - Cardoso, Marta
AU - Neuhausen, Susan L
AU - Steele, Linda
AU - Ding, Yuan Chun
AU - De Ruyck, Kim
AU - De Meerleer, Gert
AU - Ost, Piet
AU - Razack, Azad
AU - Lim, Jasmine
AU - Teo, Soo-Hwang
AU - Lin, Daniel W
AU - Newcomb, Lisa F
AU - Lessel, Davor
AU - Gamulin, Marija
AU - Kulis, Tomislav
AU - Kaneva, Radka
AU - Usmani, Nawaid
AU - Singhal, Sandeep
AU - Slavov, Chavdar
AU - Mitev, Vanio
AU - Parliament, Matthew
AU - Claessens, Frank
AU - Joniau, Steven
AU - Van den Broeck, Thomas
AU - Larkin, Samantha
AU - Townsend, Paul A
AU - Aukim-Hastie, Claire
AU - Dominguez, Manuela Gago
AU - Castelao, Jose Esteban
AU - Martinez, Maria Elena
AU - Roobol, Monique J
AU - Jenster, Guido
AU - van Schaik, Ron H N
AU - Menegaux, Florence
AU - Truong, Thérèse
AU - Koudou, Yves Akoli
AU - Xu, Jianfeng
AU - Khaw, Kay-Tee
AU - Cannon-Albright, Lisa
AU - Pandha, Hardev
AU - Michael, Agnieszka
AU - Thibodeau, Stephen N
AU - McDonnell, Shannon K
AU - Schaid, Daniel J
AU - Lindstrom, Sara
AU - Turman, Constance
AU - Ma, Jing
AU - Hunter, David J
AU - Riboli, Elio
AU - Siddiq, Afshan
AU - Canzian, Federico
AU - Kolonel, Laurence N
AU - Le Marchand, Loic
AU - Hoover, Robert N
AU - Machiela, Mitchell J
AU - Cui, Zuxi
AU - Kraft, Peter
AU - Amos, Christopher I
AU - Conti, David V
AU - Easton, Douglas F
AU - Wiklund, Fredrik
AU - Chanock, Stephen J
AU - Henderson, Brian E
AU - Kote-Jarai, Zsofia
AU - Haiman, Christopher A
AU - Eeles, Rosalind A
AU - Profile Study
AU - Australian Prostate Cancer BioResource (APCB)
AU - IMPACT Study
AU - Canary PASS Investigators
AU - Breast and Prostate Cancer Cohort Consortium (BPC3)
AU - PRACTICAL Consortium
AU - Cancer of the Prostate in Sweden (CAPS)
AU - Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS)
AU - Genetic Associations and Mechanisms in Oncology Consortium (GAME-ON)
AU - Elucidating Loci Involved in Prostate Cancer Susceptibility Consortium (ELLIPSE)
PY - 2018/7
Y1 - 2018/7
N2 - 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 1 .
AB - 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 1 .
KW - Journal Article
U2 - 10.1038/s41588-018-0142-8
DO - 10.1038/s41588-018-0142-8
M3 - Other (editorial matter etc.)
C2 - 29892016
VL - 50
SP - 928
EP - 936
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 7
ER -