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

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 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 AlyJohanna Schleutker, Csilla Sipeky, Teuvo 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

Research output: Contribution to journalArticle

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 & Prevention
Early online date24 Jun 2020
DOIs
Publication statusEarly online date - 24 Jun 2020
Externally publishedYes

Bibliographical note

Copyright ©2020, American Association for Cancer Research.

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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. E., Donovan, J. L., Hamdy, F. C., Parsons, J. K. K., Eeles, R. A., Easton, D. F., Kote-Jarai, Z., Amin Al Olama, A., Benlloch Garcia, S., Muir, K., Grönberg, H., Wiklund, F., ... Seibert, T. M. (2020). A genetic risk score to personalize prostate cancer screening, applied to population data. Cancer Epidemiology Biomarkers & Prevention. https://doi.org/10.1158/1055-9965.EPI-19-1527