Largest, Most Diverse Prostate Cancer Study Shows Genetic Role in Health Disparities
by Wayne Lewis
Health disparities occur in prostate cancer: risk for the disease is about 75% higher and is more than twice as deadly in Black men compared with white men. Yet white men are often overrepresented as research participants, making these differences difficult to understand and, ultimately, address.
With this problem in mind, scientists at the USC Center for Genetic Epidemiology and the Institute for Cancer Research in London led a study that brings together data from the majority of genomic prostate cancer studies globally. Including more than 200,000 men of European, African, Asian and Hispanic ancestry from around the world, the study is the largest, most diverse genetic analysis ever conducted for prostate cancer — and possibly for any other cancer.
The paper appeared in Nature Genetics.
The study’s authors identified 86 new genetic variations that increase risk for prostate cancer, not previously discovered, bringing the total number of risk loci for prostate cancer to 269. Applying a model for assessing prostate cancer risk based on the interplay of these genetic factors, the researchers showed that men of African ancestry inherit about twice the prostate cancer risk on average compared to men of European ancestry, while men of Asian ancestry inherit about three-quarter the risk of their white counterparts — evidence that genetics play some part in the differences in how often cancer occurs in different racial groups.
This research is also a step toward applying precision medicine to early detection.
“Our long-term objective is to develop a genetic risk score that can be used to determine a man’s risk of developing prostate cancer,” said corresponding author Christopher Haiman, ScD, professor of preventive medicine at the Keck School of Medicine of USC and director of the USC Center for Genetic Epidemiology. “Men at higher risk may benefit from earlier and more frequent screening, so the disease can be identified when it’s more treatable.”
Study tackles health disparities
Haiman and his colleagues used genomic datasets from countries including the U.S., the UK, Sweden, Japan, and Ghana to compare 107,247 men with prostate cancer to a control group comprising 127,006 men. By examining a spectrum of races and ethnicities, the study’s authors aim to make the genetic risk score more useful for more people.
“We not only found new markers of risk, but also demonstrated that, by combining genetic information across populations, we were able to identify a risk profile that can be applied across populations,” said Haiman. “This emphasizes the value of adding multiple racial and ethnic populations into genetic studies.”
Risk score could contribute to better screening
The PSA test’s value as a screening tool would grow if it were deployed selectively to monitor people found to be at high risk for prostate cancer — which is where the genetic risk score could come into play. Those at particularly high risk might even begin screening before age 55.
In order to translate the current research findings into better early detection, a large-scale clinical trial would be needed.
“Most important, unlike previous screening trials, this one would need to be more representative of the diversity we see in the world,” Haiman said. “No population should get left behind.”
The full version of this article originally appeared on the Keck School of Medicine website.
Dr. Catalona’s Involvement with this Research
Dr. Catalona has pledged to contribute DNA samples from his research projects to further this important work. He has also collaborated with Dr. Haiman on several studies on the genetics of prostate cancer aggressiveness and is currently an official collaborator in a recently funded NIH grant on the genetics of prostate cancer in Black men.