A polygenic score for prediction of aggressive and fatal prostate cancer in multi-ethnic populations
Description: When detected in its early stages, prostate cancer is curable, but it still causes over 350,000 deaths per year. Screening with a blood test to measure prostate-specific antigen (PSA) leads to earlier detection and has been shown to reduce cancer deaths. However, PSA testing of the entire male population leads to many false positives and many diagnoses of slow-growing cancers that are unlikely to cause significant problems. A test is needed to help physicians decide whether a given patient would benefit from screening—and what age to start that screening. Such personalized decisions might be made by measuring each man’s genetic risk for aggressive forms of prostate cancer. A genetic score (called a polygenic hazard score, or PHS) has been developed and tested in a dataset of thousands of men. The PHS was strongly associated with aggressive prostate cancer. While promising, the PHS was developed and validated with only data from men of European ancestry, reflecting data availability at the time.
We have obtained access to a large, multi-ethnic dataset, through collaboration with the international PRACTICAL consortium. We propose here to test the original PHS to see whether it performs well in a new dataset and whether performance is affected by race/ethnicity. Rather than self-reported race/ethnicity, we will use genetic ancestry (European, African, or Asian) determined by the individual’s own DNA. We will evaluate whether PHS is associated with age at diagnosis of aggressive prostate cancer and with lifetime risk of death from prostate cancer. PHS will be compared to family history and other risk factors for prostate cancer. Our preliminary results suggest that the original PHS works in men of multiple racial/ethnic backgrounds, but performance is best in genetic Europeans.
After formally testing the original PHS in each genetic subgroup, we will use the multi-ethnic data to optimize the score for each genetic ancestry. We will do this by searching for genetic markers within each genetic ancestry that are associated with age of onset of prostate cancer and incorporating them into an enhanced PHS.
Ultimately, PHS could guide personalized prostate cancer screening decisions for men of all races/ethnicities, thus saving lives through early detection.
Amount: $75,000
Funding type: grant
Funder scheme: Faculty Seed Grants
Start date: 2020-10-01
End date: 2021-09-30
Investigator: Tyler Seibert
Institution: UC San Diego
Funded outputs count: 0
Funder award ID: C21CR2060
OpenAlex ID: G8004052785