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

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; The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

doi:10.1038/s41467-021-21287-0

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

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, The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

Research output: Contribution to journal › Article › Research › peer-review

Abstract

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 80^th/20^th 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.

Original language	English
Article number	1236
Pages (from-to)	1-9
Number of pages	9
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21287-0
Publication status	Published - 23 Feb 2021
Externally published	Yes

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Polygenic hazard score is associated with prostate cancer in multi-ethnic populationsFinal published version, 1.1 MBLicence: CC BY

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Huynh-Le, M. P., Fan, C. C., Karunamuni, R., Thompson, W. K., Martinez, M. E., Eeles, R. A., Kote-Jarai, Z., Muir, K., Schleutker, J., Pashayan, N., Batra, J., & The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium (2021). Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. Nature Communications, 12(1), 1-9. Article 1236. https://doi.org/10.1038/s41467-021-21287-0

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abstract = "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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month = feb,

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doi = "10.1038/s41467-021-21287-0",

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Huynh-Le, MP, Fan, CC, Karunamuni, R, Thompson, WK, Martinez, ME, Eeles, RA, Kote-Jarai, Z, Muir, K, Schleutker, J, Pashayan, N, Batra, J & The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium 2021, 'Polygenic hazard score is associated with prostate cancer in multi-ethnic populations', Nature Communications, vol. 12, no. 1, 1236, pp. 1-9. https://doi.org/10.1038/s41467-021-21287-0

TY - JOUR

T1 - Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

AU - Huynh-Le, Minh Phuong

AU - Fan, Chun Chieh

AU - Karunamuni, Roshan

AU - Thompson, Wesley K.

AU - Martinez, Maria Elena

AU - Eeles, Rosalind A.

AU - Kote-Jarai, Zsofia

AU - Muir, Kenneth

AU - Schleutker, Johanna

AU - Pashayan, Nora

AU - Batra, Jyotsna

AU - The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

AU - Grönberg, Henrik

AU - Neal, David E.

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Martin, Richard M.

AU - Nielsen, Sune F.

AU - Nordestgaard, Børge G.

AU - Wiklund, Fredrik

AU - Tangen, Catherine M.

AU - Giles, Graham G.

AU - Wolk, Alicja

AU - Albanes, Demetrius

AU - Travis, Ruth C.

AU - Blot, William J.

AU - Zheng, Wei

AU - Sanderson, Maureen

AU - Stanford, Janet L.

AU - Mucci, Lorelei A.

AU - West, Catharine M.L.

AU - Kibel, Adam S.

AU - Cussenot, Olivier

AU - Berndt, Sonja I.

AU - Koutros, Stella

AU - Sørensen, Karina Dalsgaard

AU - Cybulski, Cezary

AU - Grindedal, Eli Marie

AU - Menegaux, Florence

AU - Khaw, Kay Tee

AU - Park, Jong Y.

AU - Ingles, Sue A.

AU - Maier, Christiane

AU - Hamilton, Robert J.

AU - Thibodeau, Stephen N.

AU - Rosenstein, Barry S.

AU - Lu, Yong Jie

AU - Watya, Stephen

AU - Vega, Ana

AU - Kogevinas, Manolis

AU - Penney, Kathryn L.

AU - Huff, Chad

AU - Teixeira, Manuel R.

AU - Multigner, Luc

AU - Leach, Robin J.

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - John, Esther M.

AU - Kaneva, Radka

AU - Logothetis, Christopher J.

AU - Neuhausen, Susan L.

AU - De Ruyck, Kim

AU - Pandha, Hardev

AU - Razack, Azad

AU - Newcomb, Lisa F.

AU - Fowke, Jay H.

AU - Gamulin, Marija

AU - Usmani, Nawaid

AU - Claessens, Frank

AU - Gago-Dominguez, Manuela

AU - Townsend, Paul A.

AU - Bush, William S.

AU - Roobol, Monique J.

AU - Parent, Marie Élise

AU - Hu, Jennifer J.

AU - Mills, Ian G.

AU - Andreassen, Ole A.

AU - Dale, Anders M.

AU - Seibert, Tyler M.

PY - 2021/2/23

Y1 - 2021/2/23

N2 - 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.

AB - 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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U2 - 10.1038/s41467-021-21287-0

DO - 10.1038/s41467-021-21287-0

M3 - Article

C2 - 33623038

AN - SCOPUS:85101701053

SN - 2041-1723

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EP - 9

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1236

ER -

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

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