Polygenic hazard score predicts risk for metastatic, fatal prostate cancer across groups
SAN FRANCISCO — A novel risk-prediction tool based on 290 genetic variants correctly identified men with high or low lifetime risks for developing metastatic or fatal prostate cancer, according to a study presented at ASCO Genitourinary Cancers Symposium.
The polygenic hazard score, known as PHS290, could be used to guide screening decisions for men of various ancestries, especially those of African ancestry, according to Meghana S. Pagadala, of the VA Health Care System in La Jolla, California, and an MD/PhD candidate at University of California, San Diego.
Data derived from Pagadala MS, et al. Abstract 155. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 17-19, 2022; San Francisco.
“A major limitation of genetic studies in prostate cancer is the exclusive focus on European men,” Pagadala told Healio. “This is especially worrisome for men of African ancestry, who have a higher incidence of metastatic and fatal prostate cancer than men of European and Asian ancestry. ... In this study, we wanted to validate the ability of the polygenic hazard score to identify men at risk [for] metastatic or fatal prostate cancer within the Million Veteran Program, one of the largest and most racially and ethnically diverse populations studied to date.”
Pagadala and colleagues obtained clinical data on 582,515 men (median age, 69 years) enrolled in the program. About 73% had European ancestry, whereas about 18% had African ancestry and the remainder had Hispanic or Asian ancestry.
Researchers used genotype data to compile scores from the PHS290 algorithm. The scores can be calculated from a single saliva sample at any point in a man’s life, Pagadala said.
“Compared with other available tests, the PHS290 score was developed to predict age-specific prostate cancer risk,” she told Healio. “This is especially appropriate as prostate cancer is highly age-dependent, with very low incidence before age 50 years and increasing exponentially as men get older.”
Researchers also evaluated family history of prostate cancer in addition to ancestry group.
Age at death due to prostate cancer served as the primary outcome, with age at diagnosis of prostate cancer metastases as a key secondary outcome. Researchers tested associations using Cox regression.
Results showed men with scores in the top 20% for genetic risk had a 4.41 (95% CI: 3.9-5.02) times higher risk for prostate cancer death than men with scores in the lowest 20%. They also had a 5.66 times higher risk for developing prostate cancer and a 4.18 times higher risk for metastatic disease than men in the bottom 20% of scores.
Among ancestral groups, men of African ancestry had the highest risks for developing prostate cancer (HR = 1.84; 95% CI, 1.79-1.9), metastatic disease (HR = 2.27; 95% CI, 2.09-2.46) and death (HR = 1.97; 95% CI, 1.67-2.29) compared with men of European ancestry. Risk among those of Hispanic ancestry appeared similar to that of men of European ancestry, and a reliable estimate of risk among men of Asian ancestry could not be determined because of the small population size in the analysis.
Family history of prostate cancer also conferred a greater risk for prostate cancer development (HR = 1.9; 95% CI, 1.84-1.97) and death due to the disease (HR = 1.67; 95% CI, 1.4-1.99)
“We were excited by the performance of PHS290 in diverse ancestry groups in the Million Veteran Program.” Pagadala said. “PHS290 was significantly associated with metastatic and fatal prostate even when controlling for family history and ancestry in a multivariable model.”
The researchers now hope to validate PHS290 using improved ancestry and admixture estimation in the veteran program, Pagadala said.
“Furthermore, we want to improve the model by including other important clinical prostate cancer screening methods, such as PSA, Gleason score and physical exam results, and continue to improve the genetic score, particularly in less studied non-European populations,” she said.
References:
- New genetic risk score stratifies lifetime risk of dying of prostate cancer in diverse populations. www.asco.org/about-asco/press-center/news-releases/new-genetic-risk-score-stratifies-lifetime-risk-dying-prostate. Published Feb. 14, 2022. Accessed Feb. 14, 2022.
- Pagadala MS, et al. Abstract 155. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 17-19, 2022; San Francisco.
Collapse
Pagadala MS, et al. Abstract 155. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 17-19, 2022; San Francisco.