Reliability of Ancestry-specific Prostate Cancer Genetic Risk Score in Four Racial and Ethnic Populations.
Eur Urol Open Sci
; 45: 23-30, 2022 Nov.
Article
en En
| MEDLINE
| ID: mdl-36353656
ABSTRACT
Background:
Reliability of prostate cancer (PCa) genetic risk score (GRS), that is, the concordance between its estimated risk and observed risk, is required for genetic testing at the individual level. Reliability data are lacking for non-European racial/ethnic populations, which hinders its clinical use and exacerbates racial disparity.Objective:
To calibrate PCa ancestry-specific GRS in four racial/ethnic populations. Design setting andparticipants:
PCa ancestry-specific GRSs, calculated from published risk-associated single-nucleotide polymorphisms in corresponding racial/ethnic populations, were evaluated in men who participated in 23andMe, Inc. genetic testing and consented for research, including 888 086 of European (EUR), 81 109 of Hispanic (HIS), 30 472 of African (AFR), and 13 985 of East Asian (EAS) ancestry, as classified by 23andMe's ancestry composition algorithm. Outcome measurements and statisticalanalysis:
The concordance between the observed and estimated PCa risks at ten ancestry-specific GRS deciles was measured primarily by using the calibration slope (ß), where 1 represents a perfect calibration. Platt scaling was used to correct the systematic bias of GRS. Results andlimitations:
A linear trend of an increased observed PCa prevalence in men with higher ancestry-specific GRS deciles was found in each racial population (all p -trend < 0.001). A calibration analysis revealed a systematic bias of GRS; ß was considerably lower than 1 (0.73, 0.64, 0.66, and 0.75 in EUR, HIS, AFR, and EAS ancestries, respectively). This bias was reduced after the Platt scaling correction ß for scaled GRS in the testing dataset (40% of individuals) approximated 1 for all groups (0.95, 1.05, 1.02, and 1.01 in EUR, HIS, AFR, and EAS populations, respectively). The generalizability of the Platt correction needs to be validated in independent cohorts.Conclusions:
A systematic bias of ancestry-specific GRS in the direction of an overestimated risk for men in the highest decile was found in EUR and non-EUR populations. GRS is well calibrated after correction and is appropriate for genetic testing at the individual level for personalized PCa screening. Patientsummary:
A corrected genetic risk score is more reliable (supported by the observed prostate cancer [PCa] risk) and appropriate for genetic testing for personalized PCa screening.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Eur Urol Open Sci
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos