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

Research output: Contribution to journalArticle (Academic Journal)

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 languageEnglish
JournalCancer Epidemiology, Biomarkers and Prevention
Early online date24 Jun 2020
DOIs
Publication statusE-pub ahead of print - 24 Jun 2020

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