TY  - JOUR
AU  - Huynh-Le, Minh-Phuong
AU  - Fan, Chun Chieh
AU  - Karunamuni, Roshan
AU  - Walsh, Eleanor I
AU  - Turner, Emma L
AU  - Lane, J Athene
AU  - Martin, Richard M
AU  - Neal, David E
AU  - Donovan, Jenny L
AU  - Hamdy, Freddie C
AU  - Parsons, J Kellogg Kellogg
AU  - Eeles, Rosalind A
AU  - Easton, Douglas F
AU  - Kote-Jarai, Zsofia
AU  - Amin Al Olama, Ali
AU  - Benlloch Garcia, Sara
AU  - Muir, Kenneth
AU  - Grönberg, Henrik
AU  - Wiklund, Fredrik
AU  - Aly, Markus
AU  - Schleutker, Johanna
AU  - Sipeky, Csilla
AU  - Tammela, Teuvo
AU  - Nordestgaard, Børge Grønne
AU  - Key, Timothy J
AU  - Travis, Ruth C
AU  - Pharoah, Paul D P
AU  - Pashayan, Nora
AU  - Khaw, Kay-Tee
AU  - Thibodeau, Stephen N
AU  - McDonnell, Shannon K
AU  - Schaid, Daniel J
AU  - Maier, Christiane
AU  - Vogel, Walther
AU  - Luedeke, Manuel
AU  - Herkommer, Kathleen
AU  - Kibel, Adam S
AU  - Cybulski, Cezary
AU  - Wokolorczyk, Dominika
AU  - Kluzniak, Wojciech
AU  - Cannon-Albright, Lisa A
AU  - Brenner, Hermann
AU  - Schöttker, Ben
AU  - Holleczek, Bernd
AU  - Park, Jong Y
AU  - Sellers, Thomas A
AU  - Lin, Hui-Yi
AU  - Slavov, Chavdar Kroumov
AU  - Kaneva, Radka P
AU  - Mitev, Vanio I
AU  - Batra, Jyotsna
AU  - Clements, Judith A
AU  - Spurdle, Amanda B
AU  - Teixeira, Manuel R
AU  - Paulo, Paula
AU  - Maia, Sofia
AU  - Pandha, Hardev
AU  - Michael, Agnieszka
AU  - Mills, Ian G
AU  - Andreassen, Ole A
AU  - Dale, Anders M
AU  - Seibert, Tyler M
TI  - A genetic risk score to personalize prostate cancer screening, applied to population data.
JO  - Cancer epidemiology, biomarkers & prevention
VL  - 29
IS  - 9
SN  - 1538-7755
CY  - Philadelphia, Pa.
PB  - AACR
M1  - DKFZ-2020-01118
SP  - 1731-1738
PY  - 2020
N1  - 2020 Sep;29(9):1731-1738
AB  - 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.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.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.PHS provides individualized estimates of risk-equivalent age for clinically significant prostate cancer. Screening initiation could be adjusted by a man's PHS.Personalized genetic risk assessments could inform prostate cancer screening decisions.
LB  - PUB:(DE-HGF)16
C6  - pmid:32581112
DO  - DOI:10.1158/1055-9965.EPI-19-1527
UR  - https://inrepo02.dkfz.de/record/156801
ER  -