A novel screening algorithm based on a polygenic hazard score that integrated 290 genetic variants (PHS290) was able to accurately stratify a diverse population of patients for their lifetime risk of developing metastatic or fatal prostate cancer.1
The PHS290 scoring algorithm revealed a differential genetic risk for prostate cancer among men of differing ancestries. Notably, men of African ancestry were estimated to have the greatest risk of developing metastatic prostate cancer and dying from the disease compared with men of other ancestries.
The results were presented at the ASCO Genitourinary Cancers Symposium 2022 by Meghana Pagadala of VA Health Care System in La Jolla, California.
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“Compared to other tests of risk, the scoring algorithm uses nearly 300 variants linked to inherited genetic information, whereas some currently available commercial tests rely on expression of just a dozen or so cancer-related genes and a handful of reference genes,” said Pagadala in a news release.2
Pagadala commented that previous genetic risk models were primarily developed from European ancestral backgrounds and may exacerbate existing health disparities in prostate cancer incidence and outcomes.
With their study, Pagadala and colleagues sought to determine if PHS290 is associated with the risk of metastatic or fatal prostate cancer in a racially and ethnically diverse population.
The effectiveness of PHS290 was evaluated in a large multi-ancestry cohort of 582,515 individuals who participated in the Million Veteran Program of the VA Health Care System.
The participants were grouped into European, African, Hispanic, or Asian ancestries. The polygenic hazard score was derived from the participants’ genotype dosage for 290 single nucleotide polymorphisms. The 3 clinical endpoints of the study were the age at diagnosis of prostate cancer, age at diagnosis of metastatic prostate cancer, and age at death from prostate cancer.
Results showed a strong association of PHS290 risk score with age at death from prostate cancer, metastatic prostate cancer, and any prostate cancer in the entire dataset and in each of the 4 ancestry groups (P <10-16).
Men in the top 20% of PHS290 score had a 4.41 (95% CI, 3.9-5.02) times higher risk of death compared with those whose genetic risk score was in the lowest 20%. In addition, men in the top 20% of PHS290 score had a 5.7 times higher risk of developing prostate cancer and 4.2 times higher risk of developing metastatic prostate cancer compared with those in the lowest 20% (P <10-16).
In a multivariate model, the corresponding hazard ratios for death from prostate cancer were 4.26 (95% CI, 3.66-4.9) for European ancestry, 2.4 (95% CI, 1.77-3.23) for African ancestry, 4.72 (95% CI, 2.68-8.87) for Hispanic ancestry, and 10.46 (95% CI, 2.01-101.0) for Asian ancestry.
Even when accounting for family history and ancestry group, PHS290 remained a strong independent predictor of death from prostate cancer.
On average, the PHS290 risk score was higher among men with African ancestry and was associated with metastasis. Men of African ancestry had a 1.8 times higher risk of prostate cancer, 2.3 times higher risk of developing metastatic prostate cancer, and 1.9 times higher risk of dying from prostate cancer compared with other ancestries (P <10-16).
In conclusion, the research team wrote that “PHS290 stratified US veterans of diverse ancestry for lifetime risk of metastatic or fatal prostate cancer. Predicting genetic risk of lethal prostate cancer with PHS290 might inform individualized decisions about prostate cancer screening.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
References
- Pagadala M, Lynch JA, Karunamuni R, et al. Evaluating a polygenic hazard score to predict risk of developing metastatic or fatal prostate cancer in the multi-ancestry Million Veteran Program cohort. Presented at ASCO GU 2022; February 17-19, 2022. Abstract 155.
- New Genetic Risk Score Stratifies Lifetime Risk of Dying of Prostate Cancer in Diverse Populations. News Release. American Society of Clinical Oncology (ASCO). February 14, 2022. Accessed February 17, 2022. https://www.asco.org/about-asco/press-center/news-releases/new-genetic-risk-score-stratifies-lifetime-risk-dying-prostate
This article originally appeared on Cancer Therapy Advisor
