TY - JOUR
T1 - A Genetic Risk Score to Personalize Prostate Cancer Screening, Applied to Population Data
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
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 Lj
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 - Australian Prostate Cancer BioResource (APCB)
N1 - ©2020 American Association for Cancer Research.
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85096010016&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-19-1527
DO - 10.1158/1055-9965.EPI-19-1527
M3 - Journal article
C2 - 32581112
SN - 1055-9965
VL - 29
SP - 1731
EP - 1738
JO - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
IS - 9
ER -