The polygenic hazard rating improves the prediction of prostate most cancers threat in multiethnic populations

Building on previous research, an international team led by scientists from the University of California’s San Diego School of Medicine has validated a more comprehensive and comprehensive genetic tool for predicting the age of onset of aggressive prostate cancer, a disease that killed more than 33,000 American men in 2020 .

In the February 23, 2021 online edition of Nature Communications, researchers describe the performance of a polygenic hazard score (PHS) – a mathematical estimate of an individual’s age-specific genetic risk for developing a disease – in a multiethnic patient population.

Genetic tools to predict a man’s lifelong risk of prostate cancer could allow us to target cancer screening to the men who are most likely to need it. We are addressing a major public health issue while also addressing the concern that genomics and genetic testing could exacerbate health disparities, as people of non-European descent are severely underrepresented in most studies. ”

Tyler Seibert, MD, PhD, principal investigator, assistant professor at UC San Diego Medical School, and radiation oncologist at UC San Diego Health’s Moores Cancer Center

The genetic score developed at UC San Diego was tested on a multiethnic dataset of 80,491 men and was shown to be related to the age of onset of prostate cancer as well as age at death from prostate cancer. The PHS showed excellent performance in men of European, Asian, and African genetic ancestry, the authors said.

However, according to Seibert, there was a clear gap between men of African and European descent. Most likely, he said, because men of African descent were not involved in developing the genetic tool.

In a study published in the International Journal of Cancer in 2020, Seibert and a team of researchers including Roshan Karunamuni, PhD, associate project scientist at the University of San Diego Medical School, identified genetic markers for prostate cancer risk that could be particularly useful for men of African descent .

The addition of these new genetic markers to the PHS resulted in improved performance in identifying African ancestry men at the highest risk of prostate cancer and made the results more comparable to those of the other ancestry groups, said Dr. Minh-Phuong Huynh-Le. He is the lead author of the Nature Communications paper and was a resident physician at UC San Diego Health during the study. Huynh-Le is now an Assistant Professor at the George Washington University School of Medicine and Health Sciences.

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

While the PHS has improved risk stratification, more needs to be done, Seibert said. Much of the data currently used for research is still not represented differently. Even in the data for this study, researchers found that most men of African genetic ancestry lacked clinical diagnostic information that was used to determine disease aggressiveness.

“This is of particular concern as race and ethnicity play an important role in prostate cancer risk. It is important that we ensure that these tools are suitable for men of all ethnic and racial backgrounds,” said Seibert. “These two papers are important steps towards that goal.”

Source:

University of California – San Diego

Journal reference:

Huynh-Le, MP., Et al. (2021) The polygenic hazard score is associated with prostate cancer in multiethnic populations. Nature communication. doi.org/10.1038/s41467-021-21287-0.

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