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

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Huynh Le, MP (Author) Other; Fan, CC (Author) Other; Karunamuni, R (Author) Other; Walsh, EI (Author) Other; Turner, EL (Author) Other; Lane, JA (Author) Other; Martin, RM (Author) Other; Neal, DE (Author) Other; Donovan, JL (Author) Other; Hamdy, FC (Author) Other; Parsons, JK (Author) Other; Eeles, RA (Author) Other; Easton, DF (Author) Other; Kote Jarai, Z (Author) Other; Al Olama, AA (Author) Other; Garcia, SB (Author) Other; Muir, K (Author) Other; Gronberg, H (Author) Other; Wiklund, F (Author) Other; Aly, M (Author) Other; Schleutker, J (Author) Other; Sipeky, C (Author) Other; Tammela, TLJ (Author) Other; Nordestgaard, BG (Author) Other; Key, TJ (Author) Other; Travis, RC (Author) Other; Pharoah, PD (Author) Other; Pashayan, N (Author) Other; Khaw, KT (Author) Other; Thibodeau, SN (Author) Other; McDonnell, SK (Author) Other; Schaid, DJ (Author) Other; Maier, C (Author) Other; Vogel, W (Author) Other; Luedeke, M (Author) Other; Herkommer, K (Author) Other; Kibel, AS (Author) Other; Cybulski, C (Author) Other; Wokolorczyk, D (Author) Other; Kluzniak, W (Author) Other; Cannon Albright, LA (Author) Other; Brenner, H (Author) Other; Ben Schottker (Author) Other; Holleczek, B (Author) Other; Park, JY (Author) Other; Sellers, TA (Author) Other; Lin, HY (Author) Other; Slavov, CK (Author) Other; Kaneva, RP (Author) Other; Mitev, VI (Author) Other; Batra, J (Author) Other; Clements, JA (Author) Other; Spurdle, AB (Author) Other; Manuel R Teixeira (Author) ICBAS; Paulo, P (Author) Other; Maia, S (Author) Other; Pandha, H (Author) Other; Michael, A (Author) Other; Mills, IG (Author) Other; Andreassen, OA (Author) Other; Dale, AM (Author) Other; Seibert, TM (Author) Other

Journal

Title: Cancer Epidemiology Biomarkers and Prevention

Vol. 29

Pages: 1731-1738

ISSN: 1055-9965

Publisher: American Association for Cancer Research

Indexing

ISI Web of Knowledge - 15 Citations

Other information

Authenticus ID: P-00S-QDT

DOI: 10.1158/1055-9965.epi-19-1527

Abstract (EN): 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 meta-stases). 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8