| Literature DB >> 29892016 |
Fredrick R Schumacher1,2, Ali Amin Al Olama3,4, Sonja I Berndt5, Sara Benlloch6,7, Mahbubl Ahmed7, Edward J Saunders7, Tokhir Dadaev7, Daniel Leongamornlert7, Ezequiel Anokian7, Clara Cieza-Borrella7, Chee Goh7, Mark N Brook7, Xin Sheng8, Laura Fachal9,10, Joe Dennis6, Jonathan Tyrer6, Kenneth Muir11,12, Artitaya Lophatananon11,12, Victoria L Stevens13, Susan M Gapstur13, Brian D Carter13, Catherine M Tangen14, Phyllis J Goodman14, Ian M Thompson15, Jyotsna Batra16,17, Suzanne Chambers18,19, Leire Moya16,17, Judith Clements16,17, Lisa Horvath20,21, Wayne Tilley22, Gail P Risbridger23,24, Henrik Gronberg25, Markus Aly26,27, Tobias Nordström25,28, Paul Pharoah6,10, Nora Pashayan10,29, Johanna Schleutker30,31, Teuvo L J Tammela32, Csilla Sipeky30, Anssi Auvinen33, Demetrius Albanes5, Stephanie Weinstein5, Alicja Wolk34,35, Niclas Håkansson34, Catharine M L West36, Alison M Dunning10, Neil Burnet37, Lorelei A Mucci38, Edward Giovannucci38, Gerald L Andriole39, Olivier Cussenot40,41, Géraldine Cancel-Tassin40,41, Stella Koutros5, Laura E Beane Freeman5, Karina Dalsgaard Sorensen42,43, Torben Falck Orntoft42,43, Michael Borre43,44, Lovise Maehle45, Eli Marie Grindedal45, David E Neal46,47,48, Jenny L Donovan49, Freddie C Hamdy48, Richard M Martin49, Ruth C Travis50, Tim J Key50, Robert J Hamilton51, Neil E Fleshner51, Antonio Finelli52, Sue Ann Ingles8, Mariana C Stern8, Barry S Rosenstein53,54, Sarah L Kerns55, Harry Ostrer56, Yong-Jie Lu57, Hong-Wei Zhang58, Ninghan Feng59, Xueying Mao57, Xin Guo60, Guomin Wang61, Zan Sun62, Graham G Giles63,64, Melissa C Southey65, Robert J MacInnis63,64, Liesel M FitzGerald63,66, Adam S Kibel67, Bettina F Drake39, Ana Vega9, Antonio Gómez-Caamaño68, Robert Szulkin69,70, Martin Eklund25, Manolis Kogevinas71,72,73,74, Javier Llorca72,75, Gemma Castaño-Vinyals71,72,73,74, Kathryn L Penney76, Meir Stampfer76, Jong Y Park77, Thomas A Sellers77, Hui-Yi Lin78, Janet L Stanford79,80, Cezary Cybulski81, Dominika Wokolorczyk81, Jan Lubinski81, Elaine A Ostrander82, Milan S Geybels79, Børge G Nordestgaard83,84, Sune F Nielsen83,84, Maren Weischer84, Rasmus Bisbjerg85, Martin Andreas Røder86, Peter Iversen86, Hermann Brenner87,88,89, Katarina Cuk87, Bernd Holleczek90, Christiane Maier91, Manuel Luedeke91, Thomas Schnoeller92, Jeri Kim93, Christopher J Logothetis93, Esther M John94,95, Manuel R Teixeira96,97, Paula Paulo96, Marta Cardoso96, Susan L Neuhausen98, Linda Steele98, Yuan Chun Ding98, Kim De Ruyck99, Gert De Meerleer99, Piet Ost100, Azad Razack101, Jasmine Lim101, Soo-Hwang Teo102, Daniel W Lin79,103, Lisa F Newcomb79,103, Davor Lessel104, Marija Gamulin105, Tomislav Kulis106, Radka Kaneva107, Nawaid Usmani108,109, Sandeep Singhal108,109, Chavdar Slavov110, Vanio Mitev107, Matthew Parliament108,109, Frank Claessens111, Steven Joniau112, Thomas Van den Broeck111,112, Samantha Larkin113, Paul A Townsend114, Claire Aukim-Hastie115, Manuela Gago-Dominguez116,117, Jose Esteban Castelao118, Maria Elena Martinez119, Monique J Roobol120, Guido Jenster120, Ron H N van Schaik121, Florence Menegaux122, Thérèse Truong122, Yves Akoli Koudou122, Jianfeng Xu123, Kay-Tee Khaw124, Lisa Cannon-Albright125,126, Hardev Pandha115, Agnieszka Michael115, Stephen N Thibodeau127, Shannon K McDonnell128, Daniel J Schaid128, Sara Lindstrom80, Constance Turman129, Jing Ma76, David J Hunter129, Elio Riboli130, Afshan Siddiq131, Federico Canzian132, Laurence N Kolonel133, Loic Le Marchand133, Robert N Hoover5, Mitchell J Machiela5, Zuxi Cui134, Peter Kraft129, Christopher I Amos135,136,137, David V Conti8, Douglas F Easton6,10, Fredrik Wiklund25, Stephen J Chanock5, Brian E Henderson8, Zsofia Kote-Jarai7, Christopher A Haiman8, Rosalind A Eeles138,139.
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 PrCa1.Entities:
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Year: 2018 PMID： 29892016 PMCID： PMC6568012 DOI： 10.1038/s41588-018-0142-8
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330