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

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PH...

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Main Authors: Huynh-Le, Minh-Phuong (Author) , Fan, Chun Chieh (Author) , Karunamuni, Roshan (Author) , Thompson, Wesley (Author) , Martinez, Maria Elena (Author) , Eeles, Rosalind A. (Author) , Kote-Jarai, Zsofia (Author) , Muir, Kenneth (Author) , Schleutker, Johanna (Author) , Pashayan, Nora (Author) , Batra, Jyotsna (Author) , Grönberg, Henrik (Author) , Neal, David E. (Author) , Donovan, Jenny L. (Author) , Hamdy, Freddie C. (Author) , Martin, Richard M. (Author) , Nielsen, Sune F. (Author) , Nordestgaard, Børge G. (Author) , Wiklund, Fredrik (Author) , Tangen, Catherine M. (Author) , Giles, Graham G. (Author) , Wolk, Alicja (Author) , Albanes, Demetrius (Author) , Travis, Ruth C. (Author) , Blot, William J. (Author) , Zheng, Wei (Author) , Sanderson, Maureen (Author) , Stanford, Janet L. (Author) , Mucci, Lorelei A. (Author) , West, Catharine M. L. (Author) , Kibel, Adam S. (Author) , Cussenot, Olivier (Author) , Berndt, Sonja I. (Author) , Koutros, Stella (Author) , Sørensen, Karina Dalsgaard (Author) , Cybulski, Cezary (Author) , Grindedal, Eli Marie (Author) , Menegaux, Florence (Author) , Khaw, Kay-Tee (Author) , Park, Jong Y. (Author) , Ingles, Sue A. (Author) , Maier, Christiane (Author) , Hamilton, Robert J. (Author) , Thibodeau, Stephen N. (Author) , Rosenstein, Barry S. (Author) , Lu, Yong-Jie (Author) , Watya, Stephen (Author) , Vega, Ana (Author) , Kogevinas, Manolis (Author) , Penney, Kathryn L. (Author) , Huff, Chad (Author) , Teixeira, Manuel R. (Author) , Multigner, Luc (Author) , Leach, Robin J. (Author) , Cannon-Albright, Lisa (Author) , Brenner, Hermann (Author) , John, Esther (Author) , Kaneva, Radka (Author) , Logothetis, Christopher J. (Author) , Neuhausen, Susan L. (Author) , De Ruyck, Kim (Author) , Pandha, Hardev (Author) , Razack, Azad (Author) , Newcomb, Lisa F. (Author) , Fowke, Jay H. (Author) , Gamulin, Marija (Author) , Usmani, Nawaid (Author) , Claessens, Frank (Author) , Gago-Dominguez, Manuela (Author) , Townsend, Paul A. (Author) , Bush, William S. (Author) , Roobol, Monique J. (Author) , Parent, Marie-Élise (Author) , Hu, Jennifer J. (Author) , Mills, Ian G. (Author) , Andreassen, Ole A. (Author) , Dalén, Anders (Author) , Seibert, Tyler M. (Author)
Format: Article (Journal)
Language:English
Published: 23 February 2021
In: Nature Communications
Year: 2021, Volume: 12, Pages: 1-9
ISSN:2041-1723
DOI:10.1038/s41467-021-21287-0
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-021-21287-0
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-021-21287-0
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Author Notes:Minh-Phuong Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Wesley K. Thompson, Maria Elena Martinez, Rosalind A. Eeles, Zsofia Kote-Jarai, Kenneth Muir, Johanna Schleutker, Nora Pashayan, Jyotsna Batra, Henrik Grönberg, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Sune F. Nielsen, Børge G. Nordestgaard, Fredrik Wiklund, Catherine M. Tangen, Graham G. Giles, Alicja Wolk, Demetrius Albanes, Ruth C. Travis, William J. Blot, Wei Zheng, Maureen Sanderson, Janet L. Stanford, Lorelei A. Mucci, Catharine M. L. West, Adam S. Kibel, Olivier Cussenot, Sonja I. Berndt, Stella Koutros, Karina Dalsgaard Sørensen, Cezary Cybulski, Eli Marie Grindedal, Florence Menegaux, Kay-Tee Khaw, Jong Y. Park, Sue A. Ingles, Christiane Maier, Robert J. Hamilton, Stephen N. Thibodeau, Barry S. Rosenstein, Yong-Jie Lu, Stephen Watya, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Chad Huff, Manuel R. Teixeira, Luc Multigner, Robin J. Leach, Lisa Cannon-Albright, Hermann Brenner, Esther M. John, Radka Kaneva, Christopher J. Logothetis, Susan L. Neuhausen, Kim De Ruyck, Hardev Pandha, Azad Razack, Lisa F. Newcomb, Jay H. Fowke, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Paul A. Townsend, William S. Bush, Monique J. Roobol, Marie-Élise Parent, Jennifer J. Hu, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert

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520 |a Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 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 80th/20th PHS2 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. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset. 
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SRT |a HUYNHLEMINPOLYGENICH2320 

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