UCSD researchers find more inclusive genetic tool to predict prostate cancer

SAN DIEGO (KUSI) – Building upon previous research, an international team led by scientists at UC San Diego School of Medicine validated a more inclusive and comprehensive genetic tool for predicting age of onset of aggressive prostate cancer, it was announced Tuesday.

Reporting in Tuesday’s online edition of Nature Communications, the researchers describe the performance of a polygenic hazard score — a mathematical estimate of an individual’s age-specific genetic risk for developing a disease — in a multi-ethnic patient population.

“Genetic tools to predict a man’s lifetime risk of prostate cancer might allow us to target cancer screening efforts to the men who are most likely to need it,” said Dr. Tyler Seibert, an assistant professor at UCSD School of Medicine and radiation oncologist at Moores Cancer Center at UCSD Health.

“We are addressing a major public health problem and simultaneously addressing a concern that genomics and genetic tests may exacerbate health disparities because people of non-European ancestry are severely under- represented in most studies,” said Seibert, the study’s principal investigator

In 2020, prostate cancer killed more than 33,000 American men and more than 240,000 men were diagnosed with the disease, according to the American Cancer Society. One in eight men will be diagnosed with prostate cancer and it is more likely to develop in older, non-Hispanic Black men.

The genetic score developed at UCSD was tested in a multi-ethnic dataset of 80,491 men and was shown to be associated with age of onset of prostate cancer, as well as with age at death from prostate cancer. The PHS demonstrated excellent performance in men of European, Asian and African genetic ancestry, the authors said.

However, according to Seibert, there was a prominent gap between men of African versus European ancestry, most likely because men of African ancestry were not included in the development of the genetic tool.

In a study published in the International Journal of Cancer in 2020, Seibert and a team of researchers, including Roshan Karunamuni, assistant project scientist at the UCSD School of Medicine, identified genetic markers for prostate cancer risk that may be specifically useful in men of African ancestry.

The addition of the new genetic markers to the PHS led to improved performance in identifying men of African ancestry at highest risk of prostate cancer and made the results more comparable to those of the other ancestry groups, said Dr. Minh-Phuong Huynh-Le, first author of the Nature Communications paper.

“With only a blood or saliva sample, a man’s genetic risk of prostate cancer can be estimated,” Huynh-Le said. “Prostate cancer screening may reduce morbidity and mortality, but it should be targeted and personalized. Those at higher genetic risk might benefit from earlier and/or more frequent prostate cancer screening, and this genetic tool could identify those individuals.”

Huynh-Le, who was a resident physician at UCSD Health during the study, is now an assistant professor at George Washington University School of Medicine and Health Sciences.

While the PHS has improved risk stratification, more needs to be done, according to Seibert, as much of the data used for research continues to lack diverse representation. Even in the data for this study, researchers noted that most men of African genetic ancestry were missing clinical diagnosis information used to determine disease aggressiveness.

“This is particularly concerning, as race and ethnicity play an important part in prostate cancer risk,” Seibert said. “It is critical that we make sure these tools are designed to perform well in men of all ethnic and racial backgrounds. These two papers are important steps toward that goal.”

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