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

Huynh-Le, M-P; Fan, CC; Karunamuni, R; Walsh, E; Turner, EL; Lane, JA; Martin, RM; ... Seibert, TM; + view all (2020) A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data. Cancer Epidemiology, Biomarkers & Prevention , 29 (9) pp. 1731-1738. 10.1158/1055-9965.EPI-19-1527. Green open access

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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: 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.

Type: Article
Title: A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data
Open access status: An open access version is available from UCL Discovery
DOI: 10.1158/1055-9965.EPI-19-1527
Publisher version: https://doi.org/10.1158/1055-9965.EPI-19-1527
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Applied Health Research
URI: https://discovery.ucl.ac.uk/id/eprint/10111664
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