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Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

Minh-Phuong Huynh-Le 1 Chun Chieh Fan 1 Roshan Karunamuni 1 Wesley Thompson 1 Maria Elena Martinez 1 Rosalind Eeles 2 Zsofia Kote-Jarai 2 Kenneth Muir 3 Johanna Schleutker 4 Nora Pashayan 5, 6 Jyotsna Batra Henrik Grönberg David Neal Jenny Donovan Freddie Hamdy Richard Martin Sune Nielsen Børge Nordestgaard Fredrik Wiklund Catherine Tangen Graham Giles Alicja Wolk Demetrius Albanes Ruth Travis William Blot Wei Zheng Maureen Sanderson Janet Stanford Lorelei Mucci Catharine West Adam Kibel Olivier Cussenot 7 Sonja Berndt Stella Koutros Karina Dalsgaard Sørensen Cezary Cybulski Eli Marie Grindedal Florence Menegaux 8 Kay-Tee Khaw Jong Park Sue Ingles Christiane Maier Robert Hamilton Stephen Thibodeau Barry Rosenstein Yong-Jie Lu Stephen Watya Ana Vega Manolis Kogevinas Kathryn Penney Chad Huff Manuel Teixeira Luc Multigner 9 Robin Leach Lisa Cannon-Albright Hermann Brenner Esther John Radka Kaneva Christopher Logothetis Susan Neuhausen Kim de Ruyck Hardev Pandha Azad Razack Lisa Newcomb Jay Fowke Marija Gamulin Nawaid Usmani Frank Claessens Manuela Gago-Dominguez Paul Townsend William Bush Monique Roobol Marie-Élise Parent Jennifer Hu Ian Mills Ole Andreassen Anders Dale 1 Tyler Seibert 1, *
Abstract : Abstract Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS 1 ) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS 2 (PHS 1 , adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS 2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10 −180 ). Comparing the 80 th /20 th PHS 2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS 2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
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Submitted on : Thursday, July 8, 2021 - 10:11:06 AM
Last modification on : Tuesday, November 16, 2021 - 4:39:53 AM
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Minh-Phuong Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Wesley Thompson, Maria Elena Martinez, et al.. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. Nature Communications, Nature Publishing Group, 2021, 12 (1), pp.1236. ⟨10.1038/s41467-021-21287-0⟩. ⟨hal-03281257⟩



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