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

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Date
2020-09
ICR Author
Kote-Jarai, Zsofia
Eeles, Rosalind
Author
Huynh-Le, M-P
Fan, CC
Karunamuni, R
Walsh, EI
Turner, EL
Lane, JA
Martin, RM
Neal, DE
Donovan, JL
Hamdy, FC
Parsons, JK
Eeles, RA
Easton, DF
Kote-Jarai, Z
Amin Al Olama, A
Benlloch Garcia, S
Muir, K
Grönberg, H
Wiklund, F
Aly, M
Schleutker, J
Sipeky, C
Tammela, TL
Nordestgaard, BG
Key, TJ
Travis, RC
Pharoah, PDP
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, LA
Brenner, H
Schöttker, B
Holleczek, B
Park, JY
Sellers, TA
Lin, H-Y
Slavov, CK
Kaneva, RP
Mitev, VI
Batra, J
Clements, JA
Spurdle, AB
Teixeira, MR
Paulo, P
Maia, S
Pandha, H
Michael, A
Mills, IG
Andreassen, OA
Dale, AM
Seibert, TM
Australian Prostate Cancer BioResource (APCB)
PRACTICAL Consortium
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Type
Journal Article
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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.
URI
https://repository.icr.ac.uk/handle/internal/3805
DOI
https://doi.org/10.1158/1055-9965.epi-19-1527
Collections
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
Subject
Australian Prostate Cancer BioResource (APCB)
PRACTICAL Consortium
Research team
Oncogenetics
Language
eng
Date accepted
2020-06-15
License start date
2020-09
Citation
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2020, 29 (9), pp. 1731 - 1738

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