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

MP Huynh-Le; CC Fan; R Karunamuni; WK Thompson; M E Martinez; RA Eeles; Z Kote-Jarai; K Muir; J Schleutker; N Pashayan; J Batra; H Grönberg; DE Neal; JL Donovan; FC Hamdy; RM Martin; SF Nielsen; BG Nordestgaard; F Wiklund; C M Tangen; GG Giles; A Wolk; D Albanes; RC Travis; WJ Blot; W Zheng; M Sanderson; J L Stanford; LA Mucci; CML West; AS Kibel; O Cussenot; SI Berndt; S Koutros; KD Sørensen; C Cybulski; EM Grindedal; F Menegaux; KTH Khaw; JY Park; SA Ingles; C Maier; RJ Hamilton; SN Thibodeau; B S Rosenstein; YJ Lu; S Watya; A Vega; M Kogevinas; KL Penney; C Huff; MR Teixeira; L Multigner; RJ Leach; L Cannon-Albright; H Brenner; EM John; R Kaneva; CJ Logothetis; SL Neuhausen; K De Ruyck; H Pandha; A Razack; LF Newcomb; JH Fowke; M Gamulin; N Usmani; F Claessens; M Gago-Dominguez; PA Townsend; WS Bush; Monique Roobol - Bouts; MÉ Parent; JJ Hu; IG Mills; OA Andreassen; AM Dale; TM Seibert

doi:10.1038/s41467-021-21287-0

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

MP Huynh-Le, CC Fan, R Karunamuni, WK Thompson, M E Martinez, RA Eeles, Z Kote-Jarai, K Muir, J Schleutker, N Pashayan, J Batra, H Grönberg, DE Neal, JL Donovan, FC Hamdy, RM Martin, SF Nielsen, BG Nordestgaard, F Wiklund, C M TangenGG Giles, A Wolk, D Albanes, RC Travis, WJ Blot, W Zheng, M Sanderson, J L Stanford, LA Mucci, CML West, AS Kibel, O Cussenot, SI Berndt, S Koutros, KD Sørensen, C Cybulski, EM Grindedal, F Menegaux, KTH Khaw, JY Park, SA Ingles, C Maier, RJ Hamilton, SN Thibodeau, B S Rosenstein, YJ Lu, S Watya, A Vega, M Kogevinas, KL Penney, C Huff, MR Teixeira, L Multigner, RJ Leach, L Cannon-Albright, H Brenner, EM John, R Kaneva, CJ Logothetis, SL Neuhausen, K De Ruyck, H Pandha, A Razack, LF Newcomb, JH Fowke, M Gamulin, N Usmani, F Claessens, M Gago-Dominguez, PA Townsend, WS Bush, Monique Roobol - Bouts, MÉ Parent, JJ Hu, IG Mills, OA Andreassen, AM Dale, TM Seibert

Clinical Chemistry

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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 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
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-21287-0
Publication status	Published - 23 Feb 2021

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Publisher Copyright:
© 2021, The Author(s).

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Huynh-Le, MP., Fan, CC., Karunamuni, R., Thompson, WK., Martinez, M. E., Eeles, RA., Kote-Jarai, Z., Muir, K., Schleutker, J., Pashayan, N., Batra, J., Grönberg, H., Neal, DE., Donovan, JL., Hamdy, FC., Martin, RM., Nielsen, SF., Nordestgaard, BG., Wiklund, F., ... Seibert, TM. (2021). Polygenic hazard score is associated with prostate cancer in multi-ethnic populations. Nature Communications, 12(1), [1236]. https://doi.org/10.1038/s41467-021-21287-0

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title = "Polygenic hazard score is associated with prostate cancer in multi-ethnic populations",

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.",

author = "MP Huynh-Le and CC Fan and R Karunamuni and WK Thompson and Martinez, {M E} and RA Eeles and Z Kote-Jarai and K Muir and J Schleutker and N Pashayan and J Batra and H Gr{\"o}nberg and DE Neal and JL Donovan and FC Hamdy and RM Martin and SF Nielsen and BG Nordestgaard and F Wiklund and Tangen, {C M} and GG Giles and A Wolk and D Albanes and RC Travis and WJ Blot and W Zheng and M Sanderson and Stanford, {J L} and LA Mucci and CML West and AS Kibel and O Cussenot and SI Berndt and S Koutros and KD S{\o}rensen and C Cybulski and EM Grindedal and F Menegaux and KTH Khaw and JY Park and SA Ingles and C Maier and RJ Hamilton and SN Thibodeau and Rosenstein, {B S} and YJ Lu and S Watya and A Vega and M Kogevinas and KL Penney and C Huff and MR Teixeira and L Multigner and RJ Leach and L Cannon-Albright and H Brenner and EM John and R Kaneva and CJ Logothetis and SL Neuhausen and {De Ruyck}, K and H Pandha and A Razack and LF Newcomb and JH Fowke and M Gamulin and N Usmani and F Claessens and M Gago-Dominguez and PA Townsend and WS Bush and {Roobol - Bouts}, Monique and M{\'E} Parent and JJ Hu and IG Mills and OA Andreassen and AM Dale and TM Seibert",

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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, Grönberg, H, Neal, DE, Donovan, JL, Hamdy, FC, Martin, RM, Nielsen, SF, Nordestgaard, BG, Wiklund, F, Tangen, CM, Giles, GG, Wolk, A, Albanes, D, Travis, RC, Blot, WJ, Zheng, W, Sanderson, M, Stanford, JL, Mucci, LA, West, CML, Kibel, AS, Cussenot, O, Berndt, SI, Koutros, S, Sørensen, KD, Cybulski, C, Grindedal, EM, Menegaux, F, Khaw, KTH, Park, JY, Ingles, SA, Maier, C, Hamilton, RJ, Thibodeau, SN, Rosenstein, BS, Lu, YJ, Watya, S, Vega, A, Kogevinas, M, Penney, KL, Huff, C, Teixeira, MR, Multigner, L, Leach, RJ, Cannon-Albright, L, Brenner, H, John, EM, Kaneva, R, Logothetis, CJ, Neuhausen, SL, De Ruyck, K, Pandha, H, Razack, A, Newcomb, LF, Fowke, JH, Gamulin, M, Usmani, N, Claessens, F, Gago-Dominguez, M, Townsend, PA, Bush, WS, Roobol - Bouts, M, Parent, MÉ, Hu, JJ, Mills, IG, Andreassen, OA, Dale, AM & Seibert, TM 2021, 'Polygenic hazard score is associated with prostate cancer in multi-ethnic populations', Nature Communications, vol. 12, no. 1, 1236. https://doi.org/10.1038/s41467-021-21287-0

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AU - Fan, CC

AU - Karunamuni, R

AU - Thompson, WK

AU - Martinez, M E

AU - Eeles, RA

AU - Kote-Jarai, Z

AU - Muir, K

AU - Schleutker, J

AU - Pashayan, N

AU - Batra, J

AU - Grönberg, H

AU - Neal, DE

AU - Donovan, JL

AU - Hamdy, FC

AU - Martin, RM

AU - Nielsen, SF

AU - Nordestgaard, BG

AU - Wiklund, F

AU - Tangen, C M

AU - Giles, GG

AU - Wolk, A

AU - Albanes, D

AU - Travis, RC

AU - Blot, WJ

AU - Zheng, W

AU - Sanderson, M

AU - Stanford, J L

AU - Mucci, LA

AU - West, CML

AU - Kibel, AS

AU - Cussenot, O

AU - Berndt, SI

AU - Koutros, S

AU - Sørensen, KD

AU - Cybulski, C

AU - Grindedal, EM

AU - Menegaux, F

AU - Khaw, KTH

AU - Park, JY

AU - Ingles, SA

AU - Maier, C

AU - Hamilton, RJ

AU - Thibodeau, SN

AU - Rosenstein, B S

AU - Lu, YJ

AU - Watya, S

AU - Vega, A

AU - Kogevinas, M

AU - Penney, KL

AU - Huff, C

AU - Teixeira, MR

AU - Multigner, L

AU - Leach, RJ

AU - Cannon-Albright, L

AU - Brenner, H

AU - John, EM

AU - Kaneva, R

AU - Logothetis, CJ

AU - Neuhausen, SL

AU - De Ruyck, K

AU - Pandha, H

AU - Razack, A

AU - Newcomb, LF

AU - Fowke, JH

AU - Gamulin, M

AU - Usmani, N

AU - Claessens, F

AU - Gago-Dominguez, M

AU - Townsend, PA

AU - Bush, WS

AU - Roobol - Bouts, Monique

AU - Parent, MÉ

AU - Hu, JJ

AU - Mills, IG

AU - Andreassen, OA

AU - Dale, AM

AU - Seibert, TM

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

SN - 2041-1723

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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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