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

Autor:	Rosalind A. Eeles, Karina Dalsgaard Sørensen, Torben F. Ørntoft, Jeri Kim, Wayne D. Tilley, Ruth C. Travis, Lorelei A. Mucci, Jenny L Donovan, Kay-Tee Khaw, Edward Giovannucci, Christopher I. Amos, Soo Hwang Teo, Claire Aukim-Hastie, Gerald L. Andriole, Linda Steele, Martin Eklund, Guomin Wang, Michael Borre, Antonio Finelli, Liesel M. FitzGerald, Thérèse Truong, Robert N. Hoover, Sandeep Singhal, Radka Kaneva, Frank Claessens, Robert Szulkin, Javier Llorca, Dominika Wokołorczyk, Esther M. John, Daniel J. Schaid, Jyotsna Batra, Kathryn L. Penney, Børge G. Nordestgaard, Catharine M L West, Hermann Brenner, Sue A. Ingles, Markus Aly, Jonathan Tyrer, Thomas J. Schnoeller, Xin Guo, Peter Iversen, Olivier Cussenot, Laurence N. Kolonel, Henrik Grönberg, Ninghan Feng, Geraldine Cancel-Tassin, Christiane Maier, David E. Neal, Marija Gamulin, Ezequiel Anokian, Christopher J. Logothetis, Shannon K. McDonnell, Lovise Maehle, Anssi Auvinen, Antonio Gómez-Caamaño, Tomislav Kuliš, Manuel Luedeke, Teuvo L.J. Tammela, Brian D. Carter, Zan Sun, Jong Y. Park, Nawaid Usmani, Ian M. Thompson, Zuxi Cui, Johanna Schleutker, Bernd Holleczek, Davor Lessel, Katarina Cuk, Eli Marie Grindedal, Milan S. Geybels, Yuan Chun Ding, Phyllis J. Goodman, Jing Ma, Paul A. Townsend, Edward J. Saunders, Melissa C. Southey, Graham G. Giles, Robert J. Hamilton, Laura Fachal, Mitchell J. Machiela, Demetrius Albanes, Gert De Meerleer, Paula Paulo, Agnieszka Michael, Yves Akoli Koudou, Janet L. Stanford, Kim De Ruyck, Thomas Van den Broeck, Tokhir Dadaev, Clara Cieza-Borrella, Sonja I. Berndt, Artitaya Lophatananon, Brian E. Henderson, Niclas Håkansson, Christopher A. Haiman, Florence Menegaux, Xueying Mao, Jan Lubinski, Elio Riboli, Paul D.P. Pharoah, David J. Hunter, Loic Le Marchand, Stephen N. Thibodeau, Fredrik Wiklund, Tobias Nordström, Thomas A. Sellers, Chee Goh, Elaine A. Ostrander, Sune F. Nielsen, Neil E. Fleshner, Neil G. Burnet, Rasmus Bisbjerg, Manuela Gago Dominguez, Csilla Sipeky, Maria Elena Martinez, Susan L. Neuhausen, Stephen J. Chanock, Hui Yi Lin, Laura E. Beane Freeman, A. Siddiq, Alicja Wolk, Gemma Castaño-Vinyals, Lisa F. Newcomb, Catherine M. Tangen, Ana Vega, Peter Kraft, Chavdar Slavov, Daniel Leongamornlert, Lisa A. Cannon-Albright, Stella Koutros, Manuel R. Teixeira, Susan M. Gapstur, Federico Canzian, Sara Lindström, Maren Weischer, Bettina F. Drake, Lisa G. Horvath, Daniel W. Lin, Jose Esteban Castelao, Yong-Jie Lu, Xin Sheng, Vanio Mitev, Ron H.N. van Schaik, Monique J. Roobol, Zsofia Kote-Jarai, Leire Moya, Alison M. Dunning, Mahbubl Ahmed, Kenneth Muir, Douglas F. Easton, Suzanne K. Chambers, Hongwei Zhang, Jianfeng Xu, Jasmine Lim, Meir J. Stampfer, Guido Jenster, Ali Amin Al Olama, Victoria L. Stevens, Sara Benlloch, Mark N. Brook, Azad Hassan Abdul Razack, Marta Cardoso, Matthew Parliament, Gail P. Risbridger, Samantha E.T. Larkin, Fredrick R. Schumacher, Martin Andreas Røder, Harry Ostrer, Judith A. Clements, Manolis Kogevinas, Barry S. Rosenstein, Steven Joniau, Richard M. Martin, Constance Turman, Mariana C. Stern, Joe Dennis, David V. Conti, Sarah L. Kerns, Adam S. Kibel, Robert J. MacInnis, Stephanie J. Weinstein, Freddie C. Hamdy, Cezary Cybulski, Nora Pashayan, Timothy J. Key, Hardev Pandha, Piet Ost
Přispěvatelé:	Urology, Clinical Chemistry, Imperial College Trust, Schumacher, Fredrick R [0000-0002-3073-7463], Apollo - University of Cambridge Repository
Rok vydání:	2018
Předmět:	0301 basic medicine Oncology Male PREDICTION Cancer of the Prostate in Sweden (CAPS) Genome-wide association study PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium VARIANTS Australian Prostate Cancer BioResource (APCB) urologic and male genital diseases DISEASE FAMILY-HISTORY PATHWAY Prostate cancer Prostate Cancer Genome-wide Association Study of Uncommon Susceptibility Loci (PEGASUS) 11 Medical and Health Sciences Genetics & Heredity RISK education.field_of_study Profile Study IMPACT Study 3. Good health prostate cancer (PrCa)-susceptibility loci Centre for Surgical Research BIOLOGICAL PATHWAYS ICEP Life Sciences & Biomedicine Medical Genetics Risk medicine.medical_specialty Genotype Population Biology Polymorphism Single Nucleotide 03 medical and health sciences MULTIPLE LOCI Breast and Prostate Cancer Cohort Consortium (BPC3) SDG 3 - Good Health and Well-being Internal medicine Genetic model Genetics medicine Humans Genetic Predisposition to Disease GENOME-WIDE ASSOCIATION education Genotyping METAANALYSIS Medicinsk genetik Genetic association Canary PASS Investigators Science & Technology IDENTIFICATION CONSORTIUM Case-control study Prostatic Neoplasms 06 Biological Sciences medicine.disease GENE Genetic Associations and Mechanisms in Oncology (GAME-ON)/Elucidating Loci Involved in Prostate Cancer Susceptibility (ELLIPSE) Consortium 030104 developmental biology Genetic Loci Relative risk Case-Control Studies genotype humans male Developmental Biology Genome-Wide Association Study
Zdroj:	Schumacher, F R, Al Olama, A A, Berndt, S I, Benlloch, S, Ahmed, M, Saunders, E J, Dadaev, T, Leongamornlert, D, Anokian, E, Cieza-Borrella, C, Goh, C, Brook, M N, Sheng, X, Fachal, L, Dennis, J, Tyrer, J, Muir, K, Lophatananon, A, Stevens, V L, Gapstur, S M, Carter, B D, Tangen, C M, Goodman, P J, Thompson, I M, Batra, J, Chambers, S, Moya, L, Clements, J, Horvath, L, Tilley, W, Risbridger, G P, Gronberg, H, Aly, M, Nordström, T, Pharoah, P, Pashayan, N, Schleutker, J, Tammela, T L J, Sipeky, C, Auvinen, A, Albanes, D, Weinstein, S, Wolk, A, Sorensen, K D, Orntoft, T F, Borre, M & Profile Study 2018, ' Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci ', Nature Genetics, vol. 50, no. 7, pp. 928-936 . https://doi.org/10.1038/s41588-018-0142-8 the Profile Study 2018, ' Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci ', Nature Genetics, vol. 50, no. 7, 8, pp. 928-936 . https://doi.org/10.1038/s41588-018-0142-8 Nature Genetics, 50(7), 928-+. Nature Publishing Group
ISSN:	1546-1718 1061-4036
Popis:	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 .
Databáze:	OpenAIRE
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