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

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

Nat Genet 2018 07 11;50(7):928-936. Epub 2018 Jun 11.

Institute of Cancer Research, London, UK.

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) 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; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10; 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.

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http://dx.doi.org/10.1038/s41588-018-0142-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568012PMC
July 2018
86 Reads
6 Citations
29.352 Impact Factor

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