Novel polygenic risk score predicts prostate cancer risk accurately across ethnicities

A novel polygenic hazard score (PHS) adapted to different genetic ancestries can be used for reliable risk-stratification among prostate cancer patients across multiple ethnicities, a recent study has found.

The researchers took an existing hazard score PHS1 and adapted it to different ethnicities from the OncoArray project. The resulting score, PHS2, was assessed for its ability to predict any, aggressive, and fatal prostate cancers. The study sample was a multi-ethnic cohort of 80,491 men, of whom 49,916 had prostate cancer and 30,575 were set as controls.

PHS2 included 46 single-nucleotide polymorphisms and displayed an association with age at aggressive prostate cancer that was comparable to PHS1. Overall, men with high PHS2 saw significantly elevated risk of actually developing prostate cancer.

For instance, those in ≥80th vs ≤20th percentile of PHS2 scores were more than five times more likely to be diagnosed with any prostate cancer (hazard ratio [HR], 5.32, 95 percent confidence interval [CI], 4.99–5.70).

Similarly, men in the highest 2 percent of genetic risk (≥98th percentile) were at significantly greater risk of prostate cancer, as compared to those in the 30th–70th percentiles (HR, 4.21, 95 percent CI, 3.99–4.47).

This effect remained significant even when tested in the different ethnicities. Asian men in the top 20 percent of PHS2 scores, for example, were over four times as likely to get diagnosed with prostate cancer than those in the bottom 20th percentile (HR, 4.49, 95 percent CI, 3.23–6.33). The same was true for African (HR, 2.54, 95 percent CI, 2.08–3.10) and European (HR, 5.54, 95 percent CI, 5.18–5.93) men.

The PHS2 was also significantly associated with the risk of aggressive prostate cancer across all ethnicities, and with the risk of death from prostate cancer in the combined cohort.

“PHS performance was relatively diminished in men of African genetic ancestry, compared to performance in men of European or Asian genetic ancestry,” the researchers said. “PHS risk-stratifies men of various genetic ancestries for prostate cancer and should be prospectively studied as a means to individualize screening strategies seeking to reduce prostate cancer morbidity and mortality.”