Genetic Data Aids Prostate Cancer Risk Prediction in Diverse Groups

Genetic data can help improve prostate cancer risk prediction in diverse racial and ethnic groups, leading to more targeted, personalized screenings, according to a study published in Nature Communications.

Researchers noted that prostate cancer is the second most common cancer diagnosed in men worldwide, causing significant morbidity and mortality. In the US alone, prostate cancer killed 33,000 men in 2020.

A group from UC San Diego set out to develop a comprehensive, inclusive genetic tool that could accurately predict age of onset of aggressive prostate cancer.

The Nature Communications study builds on past research from the UC San Diego team. In 2018, researchers developed a genetic score to predict prostate cancer. Researchers tested the tool in a multi-ethnic dataset of 80,491 men and showed that the score is associated with age of onset of prostate cancer, as well as age at death from prostate cancer.

Researchers found that the genetic score performed well in men of European, Asian, and African ancestry. However, the tool demonstrated a significant gap between men of African versus European ancestry – most likely because men of African ancestry were not included in the development of the tool.

Given the fact that African American men are twice as likely to develop prostate cancer, and more often have an aggressive form of the disease, it’s critical for tools like these to include data from this 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 principal investigator Tyler Seibert, MD, PhD, assistant professor at UC San Diego School of Medicine and radiation oncologist at Moores Cancer Center at UC San Diego 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.”

In 2020, the UC San Diego team identified genetic markers for prostate cancer that may be specifically useful in men of African ancestry. The addition of these biomarkers to the genetic risk score led to improved performance in identifying men of African ancestry at highest risk of prostate cancer.

The new biomarkers also made the results more comparable to those of other ancestry groups.

"With only a blood or saliva sample, a man's genetic risk of prostate cancer can be estimated," said Minh-Phuong Huynh-Le, MD, who is first author of the Nature Communications paper and was a resident physician at UC San Diego Health during the study.

"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."

Although the genetic tool has improved risk stratification for prostate cancer, researchers still have more work ahead of them. A lot of the data currently used for research continues to lack diverse representation. The team noted that even in the data for this study, 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. It is critical that we make sure these tools are designed to perform well in men of all ethnic and racial backgrounds," said Seibert. "These two papers are important steps toward that goal."

The research sector has increasingly focused on genetics to improve prostate cancer risk assessments and treatment. A team from Mount Sinai recently published a review in which they stated that disparities in prostate cancer likely stem from socioeconomic factors, problems with care access, and tumor biology.

The team focused on biological differences in the development of prostate cancer across ethnicities, examining the molecular and genomic differences in prostate cancer between black men and white men to highlight innovative treatments. This included immunotherapies explicitly aimed at black populations to reduce prostate cancer disparities.

“We provide a comprehensive review of the significant research in recent years that has examined the molecular and genomic reasons for unequal cancer burden in African American and Caucasian American populations and acknowledge the challenges that lie ahead,” said senior author Ashutosh K. Tewari, MD, of the Icahn School of Medicine at Mount Sinai.

“This article provides specific guidelines for managing prostate cancer in African American men based on their disease's biology and makes a significant contribution to the ongoing national effort to improve African American men's outcomes from prostate cancer.”