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A genetic risk score to personalize prostate cancer screening, applied to population data

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: Unite...

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Main Authors: Huynh-Le, Minh-Phuong (Author) , Fan, Chun Chieh (Author) , Karunamuni, Roshan (Author) , Walsh, Eleanor I. (Author) , Turner, Emma L. (Author) , Lane, J. Athene (Author) , Martin, Richard M. (Author) , Neal, David E. (Author) , Donovan, Jenny L. (Author) , Hamdy, Freddie C. (Author) , Parsons, J. Kellogg (Author) , Eeles, Rosalind A. (Author) , Easton, Douglas F. (Author) , Kote-Jarai, Zsofia (Author) , Olama, Ali Amin Al (Author) , Benlloch García, Sara (Author) , Muir, Kenneth (Author) , Grönberg, Henrik (Author) , Wiklund, Fredrik (Author) , Aly, Markus (Author) , Schleutker, Johanna (Author) , Sipeky, Csilla (Author) , Tammela, Teuvo LJ (Author) , Nordestgaard, Børge Grønne (Author) , Key, Timothy J. (Author) , Travis, Ruth C. (Author) , Pharoah, Paul D. P. (Author) , Pashayan, Nora (Author) , Khaw, Kay-Tee (Author) , Thibodeau, Stephen N. (Author) , McDonnell, Shannon K. (Author) , Schaid, Daniel J. (Author) , Maier, Christiane (Author) , Vogel, Walther (Author) , Luedeke, Manuel (Author) , Herkommer, Kathleen (Author) , Kibel, Adam S. (Author) , Cybulski, Cezary (Author) , Wokolorczyk, Dominika (Author) , Kluzniak, Wojciech (Author) , Cannon-Albright, Lisa A. (Author) , Brenner, Hermann (Author) , Schöttker, Ben (Author) , Holleczek, Bernd (Author) , Park, Jong Y. (Author) , Sellers, Thomas A. (Author) , Lin, Hui-Yi (Author) , Slavov, Chavdar Kroumov (Author) , Kaneva, Radka P. (Author) , Mitev, Vanio I. (Author) , Batra, Jyotsna (Author) , Clements, Judith A. (Author) , Spurdle, Amanda B. (Author) , Teixeira, Manuel R. (Author) , Paulo, Paula (Author) , Maia, Sofia (Author) , Pandha, Hardev (Author) , Michael, Agnieszka (Author) , Mills, Ian G. (Author) , Andreassen, Ole A. (Author) , Dale, Anders M. (Author) , Seibert, Tyler M. (Author)
Format: Article (Journal)
Language:English
Published: September 2020
In: Cancer epidemiology, biomarkers & prevention
Year: 2020, Volume: 29, Issue: 9, Pages: 1731-1738
ISSN:1538-7755
DOI:10.1158/1055-9965.EPI-19-1527
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1055-9965.EPI-19-1527
Verlag, lizenzpflichtig, Volltext: https://cebp.aacrjournals.org/content/29/9/1731
Verlag, lizenzpflichtig, Volltext: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483627
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Author Notes:Minh-Phuong Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Eleanor I. Walsh, Emma L. Turner, J. Athene Lane, Richard M. Martin, David E. 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 Garcia, Kenneth Muir, Henrik Grönberg, Fredrik Wiklund, Markus Aly, Johanna Schleutker, Csilla Sipeky, Teuvo LJ Tammela, Børge Grønne Nordestgaard, Timothy J. Key, Ruth C. Travis, Paul D. P. Pharoah, Nora Pashayan, Kay-Tee Khaw, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Christiane Maier, Walther Vogel, Manuel Luedeke, Kathleen Herkommer, Adam S. Kibel, Cezary Cybulski, Dominika Wokolorczyk, Wojciech Kluzniak, Lisa A. Cannon-Albright, Hermann Brenner, Ben Schöttker, Bernd Holleczek, Jong Y. Park, Thomas A. Sellers, Hui-Yi Lin, Chavdar Kroumov Slavov, Radka P. Kaneva, Vanio I. Mitev, Jyotsna Batra, Judith A. Clements, Amanda B. Spurdle, Manuel R. Teixeira, Paula Paulo, Sofia Maia, Hardev Pandha, Agnieszka Michael, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert

MARC

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520 |a 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: United Kingdom population incidence data (Cancer Research United Kingdom) 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 score ≥7, stage T3-T4, PSA ≥10, or nodal/distant metastases). Using HRs 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-year-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-year-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. 
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