Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

David Conti (1, 2) , Burcu Darst (1, 2) , Lilit Moss (1, 2) , Edward Saunders , Xin Sheng (1, 2) , Alisha Chou (1, 2) , Fredrick Schumacher , Ali Amin Al Olama , Sara Benlloch , Tokhir Dadaev , Mark Brook , Ali Sahimi (1, 2) , Thomas Hoffmann , Atushi Takahashi , Koichi Matsuda , Yukihide Momozawa , Masashi Fujita , Kenneth Muir , Artitaya Lophatananon , Peggy Wan (1, 2) , Loic Le Marchand , Lynne Wilkens , Victoria Stevens , Susan Gapstur , Brian Carter , Johanna Schleutker , Teuvo Tammela , Csilla Sipeky , Anssi Auvinen , Graham Giles , Melissa Southey , Robert Macinnis , Cezary Cybulski , Dominika Wokołorczyk , Jan Lubiński , David Neal , Jenny Donovan , Freddie Hamdy , Richard Martin , Børge Nordestgaard , Sune Nielsen , Maren Weischer , Stig Bojesen , Martin Andreas Røder , Peter Iversen , Jyotsna Batra , Suzanne Chambers , Leire Moya , Lisa Horvath , Judith Clements , Wayne Tilley , Gail Risbridger , Henrik Gronberg , Markus Aly , Robert Szulkin , Martin Eklund , Tobias Nordström , Nora Pashayan , Alison Dunning , Maya Ghoussaini , Ruth Travis , Tim Key , Elio Riboli , Jong Park , Thomas Sellers , Hui-Yi Lin , Demetrius Albanes , Stephanie Weinstein , Lorelei Mucci , Edward Giovannucci , Sara Lindstrom , Peter Kraft , David Hunter , Kathryn Penney , Constance Turman , Catherine Tangen , Phyllis Goodman , Ian Thompson , Robert Hamilton , Neil Fleshner , Antonio Finelli , Marie-Élise Parent , Janet Stanford , Elaine Ostrander , Milan Geybels , Stella Koutros , Laura Freeman , Meir Stampfer , Alicja Wolk , Niclas Håkansson , Gerald Andriole , Robert Hoover , Mitchell Machiela , Karina Dalsgaard Sørensen , Michael Borre , William Blot , Wei Zheng , Edward Yeboah , James Mensah , Yong-Jie Lu , Hong-Wei Zhang , Ninghan Feng , Xueying Mao , Yudong Wu , Shan-Chao Zhao , Zan Sun , Stephen Thibodeau , Shannon Mcdonnell , Daniel Schaid , Catharine West , Neil Burnet , Gill Barnett , Christiane Maier , Thomas Schnoeller , Manuel Luedeke , Adam Kibel , Bettina Drake , Olivier Cussenot (3) , Géraldine Cancel-Tassin (3) , Florence Menegaux (4) , Thérèse Truong (4) , Yves Akoli Koudou (4) , Esther John , Eli Marie Grindedal , Lovise Maehle , Kay-Tee Khaw , Sue Ingles , Mariana Stern , Ana Vega , Antonio Gómez-Caamaño , Laura Fachal , Barry Rosenstein , Sarah Kerns , Harry Ostrer , Manuel Teixeira , Paula Paulo , Andreia Brandão , Stephen Watya , Alexander Lubwama , Jeannette Bensen , Elizabeth Fontham , James Mohler , Jack Taylor , Manolis Kogevinas , Javier Llorca , Gemma Castaño-Vinyals , Lisa Cannon-Albright , Craig Teerlink , Chad Huff , Sara Strom , Luc Multigner (5) , Pascal Blanchet (6, 5) , Laurent Brureau (6, 5) , Radka Kaneva , Chavdar Slavov , Vanio Mitev , Robin Leach , Brandi Weaver , Hermann Brenner , Katarina Cuk , Bernd Holleczek , Kai-Uwe Saum , Eric Klein , Ann Hsing , Rick Kittles , Adam Murphy , Christopher Logothetis , Jeri Kim , Susan Neuhausen , Linda Steele , Yuan Chun Ding , William Isaacs , Barbara Nemesure , Anselm Hennis , John Carpten , Hardev Pandha , Agnieszka Michael , Kim de Ruyck , Gert de Meerleer , Piet Ost , Jianfeng Xu , Azad Razack , Jasmine Lim , Soo-Hwang Teo , Lisa Newcomb , Daniel Lin , Jay Fowke , Christine Neslund-Dudas , Benjamin Rybicki , Marija Gamulin , Davor Lessel , Tomislav Kulis , Nawaid Usmani , Sandeep Singhal , Matthew Parliament , Frank Claessens , Steven Joniau , Thomas van den Broeck , Manuela Gago-Dominguez , Jose Esteban Castelao , Maria Elena Martinez , Samantha Larkin , Paul Townsend , Claire Aukim-Hastie , William Bush , Melinda Aldrich , Dana Crawford , Shiv Srivastava , Jennifer Cullen , Gyorgy Petrovics , Graham Casey , Monique Roobol , Guido Jenster , Ron van Schaik , Jennifer Hu , Maureen Sanderson , Rohit Varma , Roberta Mckean-Cowdin , Mina Torres , Nicholas Mancuso , Sonja Berndt , Stephen van den Eeden , Douglas Easton , Stephen Chanock , Michael Cook , Fredrik Wiklund , Hidewaki Nakagawa , John Witte , Rosalind Eeles (7) , Zsofia Kote-Jarai (7) , Christopher Haiman (1, 2)

1 USC - University of Southern California
2 Keck School of Medicine [Los Angeles]
3 CHU Tenon [AP-HP]
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 Irset - Institut de recherche en santé, environnement et travail
6 CHU Pointe-à-Pitre/Abymes [Guadeloupe]
7 The institute of cancer research [London]

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Domaines: Génétique

David Conti, Burcu Darst, Lilit Moss, Edward Saunders, Xin Sheng, et al.. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nature Genetics, 2021, 53 (1), pp.65-75. ⟨10.1038/s41588-020-00748-0⟩. ⟨hal-03118482⟩