A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data

Minh-Phoung Huynh-Le; Chun Chieh Fan; Roshan Karunamuni; Eleanor I Walsh; Emma L Turner; J. Athene Lane; Richard M Martin; David Neal; Jenny L Donovan; Freddie C.  Hamdy; J. Kellogg Parsons; Rosalind A. Eeles; Douglas F Easton; Zsofia Kote-Jarai; Ali Amin Al Olama; Sara Benlloch; Kenneth R Muir; Henrik Gronberg; Fredrik Wiklund; Markus Aly; Johanna Schleutker; Csilla Sipeky; Teuvo L.J. Tammela; Børge G. Nordestgaard; Timothy J. Key; Ruth C Travis; Paul Pharoah; Nora Pashayan; Kay-Tee Khaw; Stephen N. Thibodeau; Shannon K. McDonnell; Daniel J. Schaid; C Maier; Walther Vogel; Manuel Luedeke; Kathleen Herkommer; Adam S. Kibel; Cezary Cybulski; Dominika Wokolorczyk; Wojciech Kluzniak; Lisa Cannon-Albright; Hermann Brenner; Ben Schöttker; Bernd Holleczek; Jong Y. Park; Thomas A. Sellers; Hui Yi Lin; Chavdar Slavov; Radka Kaneva; Vanio Mitev; Jyotsna Batra; Judith Clements; A Spurdle; Manuel R Teixeira; Paula Paulo; Sofia Maia; Hardev Pandha; Agnieszka Michael; Ian G Mills; Ole A. Andreassen; Anders M Dale; Tyler M. Seibert

doi:10.1158/1055-9965.EPI-19-1527

A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data

Minh-Phoung Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Eleanor I Walsh, Emma L Turner, J. Athene Lane, Richard M Martin, David Neal, Jenny L Donovan , Freddie C. Hamdy, J. Kellogg Parsons, Rosalind A. Eeles, Douglas F Easton, Zsofia Kote-Jarai, Ali Amin Al Olama, Sara Benlloch, Kenneth R Muir, Henrik Gronberg, Fredrik Wiklund, Markus AlyJohanna Schleutker, Csilla Sipeky, Teuvo L.J. Tammela, Børge G. Nordestgaard, Timothy J. Key, Ruth C Travis, Paul Pharoah, Nora Pashayan, Kay-Tee Khaw, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, C Maier, Walther Vogel, Manuel Luedeke, Kathleen Herkommer, Adam S. Kibel, Cezary Cybulski, Dominika Wokolorczyk, Wojciech Kluzniak, Lisa Cannon-Albright, Hermann Brenner, Ben Schöttker, Bernd Holleczek, Jong Y. Park, Thomas A. Sellers, Hui Yi Lin, Chavdar Slavov, Radka Kaneva, Vanio Mitev, Jyotsna Batra, Judith Clements, A Spurdle, Manuel R Teixeira, Paula Paulo, Sofia Maia, Hardev Pandha, Agnieszka Michael, Ian G Mills, Ole A. Andreassen, Anders M Dale, Tyler M. Seibert^*

^*Corresponding author for this work

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Abstract

Background: A polygenic hazard score (PHS)-the weighted sum of 54 SNP genotypes-was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening.
Methods: UK population incidence data (Cancer Research UK) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using hazard ratios estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age-when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-years-standard risk)-was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups.
Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-years-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age.
Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS.
Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.

Original language	English
Journal	Cancer Epidemiology, Biomarkers and Prevention
Early online date	24 Jun 2020
DOIs	https://doi.org/10.1158/1055-9965.EPI-19-1527
Publication status	E-pub ahead of print - 24 Jun 2020

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Huynh-Le, M-P., Fan, C. C., Karunamuni, R., Walsh, E. I., Turner, E. L., Lane, J. A., Martin, R. M., Neal, D., Donovan , J. L., Hamdy, F. C., Parsons, J. K., Eeles, R. A., Easton, D. F., Kote-Jarai, Z., Olama, A. A. A., Benlloch, S., Muir, K. R., Gronberg, H., Wiklund, F., ... Seibert, T. M. (2020). A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data. Cancer Epidemiology, Biomarkers and Prevention. https://doi.org/10.1158/1055-9965.EPI-19-1527

@article{dfcd35e0e74a4ba2b1a01f0dcdd04dc4,

title = "A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data",

abstract = "Background: A polygenic hazard score (PHS)-the weighted sum of 54 SNP genotypes-was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. Methods: UK population incidence data (Cancer Research UK) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using hazard ratios estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age-when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-years-standard risk)-was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-years-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.",

author = "Minh-Phoung Huynh-Le and Fan, {Chun Chieh} and Roshan Karunamuni and Walsh, {Eleanor I} and Turner, {Emma L} and Lane, {J. Athene} and Martin, {Richard M} and David Neal and Donovan, {Jenny L} and Hamdy, {Freddie C.} and Parsons, {J. Kellogg} and Eeles, {Rosalind A.} and Easton, {Douglas F} and Zsofia Kote-Jarai and Olama, {Ali Amin Al} and Sara Benlloch and Muir, {Kenneth R} and Henrik Gronberg and Fredrik Wiklund and Markus Aly and Johanna Schleutker and Csilla Sipeky and Tammela, {Teuvo L.J.} and Nordestgaard, {B{\o}rge G.} and Key, {Timothy J.} and Travis, {Ruth C} and Paul Pharoah and Nora Pashayan and Kay-Tee Khaw and Thibodeau, {Stephen N.} and McDonnell, {Shannon K.} and Schaid, {Daniel J.} and C Maier and Walther Vogel and Manuel Luedeke and Kathleen Herkommer and Kibel, {Adam S.} and Cezary Cybulski and Dominika Wokolorczyk and Wojciech Kluzniak and Lisa Cannon-Albright and Hermann Brenner and Ben Sch{\"o}ttker and Bernd Holleczek and Park, {Jong Y.} and Sellers, {Thomas A.} and Lin, {Hui Yi} and Chavdar Slavov and Radka Kaneva and Vanio Mitev and Jyotsna Batra and Judith Clements and A Spurdle and Teixeira, {Manuel R} and Paula Paulo and Sofia Maia and Hardev Pandha and Agnieszka Michael and Mills, {Ian G} and Andreassen, {Ole A.} and Dale, {Anders M} and Seibert, {Tyler M.}",

year = "2020",

month = jun,

day = "24",

doi = "10.1158/1055-9965.EPI-19-1527",

language = "English",

journal = "Cancer Epidemiology, Biomarkers and Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

}

Huynh-Le, M-P, Fan, CC, Karunamuni, R, Walsh, EI, Turner, EL , Lane, JA , Martin, RM, Neal, D, Donovan , JL, Hamdy, FC, Parsons, JK, Eeles, RA, Easton, DF, Kote-Jarai, Z, Olama, AAA, Benlloch, S, Muir, KR, Gronberg, H, Wiklund, F, Aly, M, Schleutker, J, Sipeky, C, Tammela, TLJ, Nordestgaard, BG, Key, TJ, Travis, RC, Pharoah, P, Pashayan, N, Khaw, K-T, Thibodeau, SN, McDonnell, SK, Schaid, DJ, Maier, C, Vogel, W, Luedeke, M, Herkommer, K, Kibel, AS, Cybulski, C, Wokolorczyk, D, Kluzniak, W, Cannon-Albright, L, Brenner, H, Schöttker, B, Holleczek, B, Park, JY, Sellers, TA, Lin, HY, Slavov, C, Kaneva, R, Mitev, V, Batra, J, Clements, J, Spurdle, A, Teixeira, MR, Paulo, P, Maia, S, Pandha, H, Michael, A, Mills, IG, Andreassen, OA, Dale, AM & Seibert, TM 2020, 'A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data', Cancer Epidemiology, Biomarkers and Prevention. https://doi.org/10.1158/1055-9965.EPI-19-1527

TY - JOUR

T1 - A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data

AU - Huynh-Le, Minh-Phoung

AU - Fan, Chun Chieh

AU - Karunamuni, Roshan

AU - Walsh, Eleanor I

AU - Turner, Emma L

AU - Lane, J. Athene

AU - Martin, Richard M

AU - Neal, David

AU - Donovan , Jenny L

AU - Hamdy, Freddie C.

AU - Parsons, J. Kellogg

AU - Eeles, Rosalind A.

AU - Easton, Douglas F

AU - Kote-Jarai, Zsofia

AU - Olama, Ali Amin Al

AU - Benlloch, Sara

AU - Muir, Kenneth R

AU - Gronberg, Henrik

AU - Wiklund, Fredrik

AU - Aly, Markus

AU - Schleutker, Johanna

AU - Sipeky, Csilla

AU - Tammela, Teuvo L.J.

AU - Nordestgaard, Børge G.

AU - Key, Timothy J.

AU - Travis, Ruth C

AU - Pharoah, Paul

AU - Pashayan, Nora

AU - Khaw, Kay-Tee

AU - Thibodeau, Stephen N.

AU - McDonnell, Shannon K.

AU - Schaid, Daniel J.

AU - Maier, C

AU - Vogel, Walther

AU - Luedeke, Manuel

AU - Herkommer, Kathleen

AU - Kibel, Adam S.

AU - Cybulski, Cezary

AU - Wokolorczyk, Dominika

AU - Kluzniak, Wojciech

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Schöttker, Ben

AU - Holleczek, Bernd

AU - Park, Jong Y.

AU - Sellers, Thomas A.

AU - Lin, Hui Yi

AU - Slavov, Chavdar

AU - Kaneva, Radka

AU - Mitev, Vanio

AU - Batra, Jyotsna

AU - Clements, Judith

AU - Spurdle, A

AU - Teixeira, Manuel R

AU - Paulo, Paula

AU - Maia, Sofia

AU - Pandha, Hardev

AU - Michael, Agnieszka

AU - Mills, Ian G

AU - Andreassen, Ole A.

AU - Dale, Anders M

AU - Seibert, Tyler M.

PY - 2020/6/24

Y1 - 2020/6/24

N2 - Background: A polygenic hazard score (PHS)-the weighted sum of 54 SNP genotypes-was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. Methods: UK population incidence data (Cancer Research UK) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using hazard ratios estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age-when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-years-standard risk)-was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-years-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.

AB - Background: A polygenic hazard score (PHS)-the weighted sum of 54 SNP genotypes-was previously validated for association with clinically significant prostate cancer and for improved prostate cancer screening accuracy. Here, we assess the potential impact of PHS-informed screening. Methods: UK population incidence data (Cancer Research UK) and data from the Cluster Randomized Trial of PSA Testing for Prostate Cancer were combined to estimate age-specific clinically significant prostate cancer incidence (Gleason≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using hazard ratios estimated from the ProtecT prostate cancer trial, age-specific incidence rates were calculated for various PHS risk percentiles. Risk-equivalent age-when someone with a given PHS percentile has prostate cancer risk equivalent to an average 50-year-old man (50-years-standard risk)-was derived from PHS and incidence data. Positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was calculated using PHS-adjusted age groups. Results: The expected age at diagnosis of clinically significant prostate cancer differs by 19 years between the 1st and 99th PHS percentiles: men with PHS in the 1st and 99th percentiles reach the 50-years-standard risk level at ages 60 and 41, respectively. PPV of PSA was higher for men with higher PHS-adjusted age. Conclusions: PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS. Impact: Personalized genetic risk assessments could inform prostate cancer screening decisions.

U2 - 10.1158/1055-9965.EPI-19-1527

DO - 10.1158/1055-9965.EPI-19-1527

M3 - Article (Academic Journal)

C2 - 32581112

JO - Cancer Epidemiology, Biomarkers and Prevention

JF - Cancer Epidemiology, Biomarkers and Prevention

SN - 1055-9965

ER -

A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data

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