LOS ANGELES — A multi-ancestry polygenic risk score (PRS) that stratifies prostate cancer risk across populations has been developed. In a recent study, the developers validated the performance of the PRS in the multi-ancestry Million Veteran Program and additional independent studies.
University of Southern California researchers and colleagues—including representatives from the West Haven, CT, and Boston VA Healthcare Systems—advised that, within each ancestry population, the association of PRS with prostate cancer risk was evaluated separately in each case-control study and then combined in a fixed-effects inverse-variance-weighted meta-analysis. The authors said they analyzed the effect of modification by age and estimated the age-specific absolute risk of prostate cancer for each ancestry population.
For the report in Elife, the study team evaluated the PRS in 31,925 cases and 490,507 controls.
Those included men from the following populations:
- European (22,049 cases, 414,249 controls),
- African (8794 cases, 55,657 controls) and
- Hispanic (1082 cases, 20,601 controls) populations.
“Comparing men in the top decile (90-100% of the PRS) to the average 40-60% PRS category, the prostate cancer odds ratio (OR) was 3.8-fold in European ancestry men (95% CI = 3.62-3.96), 2.8-fold in African ancestry men (95% CI = 2.59-3.03), and 3.2-fold in Hispanic men (95% CI = 2.64-3.92),” the researchers reported. “The PRS did not discriminate risk of aggressive versus non-aggressive prostate cancer. However, the OR diminished with advancing age (European ancestry men in the top decile: ≤55 years, OR = 7.11; 55-60 years, OR = 4.26; >70 years, OR = 2.79). Men in the top PRS decile reached 5% absolute prostate cancer risk ~10 years younger than men in the 40-60% PRS category.”1
The authors suggested that their findings validate the multi-ancestry PRS as an effective prostate cancer risk stratification tool across populations. They also called for a clinical study of PRS to determine whether the tool could be used for risk-stratified screening and early detection.
- Chen F, Darst BF, Madduri RK, Rodriguez AA, et. al. Validation of a multi-ancestry polygenic risk score and age-specific risks of prostate cancer: A meta-analysis within diverse populations. Elife. 2022 Jul 8;11:e78304. doi: 10.7554/eLife.78304. PMID: 35801699; PMCID: PMC9322982.