Genomic Data Analysis May Inform Prostate Cancer Risk Scores

Analyzing genomic data from diverse populations could improve prostate cancer risk scores and enable early detection of the disease, a study published in Nature Genetics revealed.

Prostate cancer is the most common type of cancer among American men after skin cancer. However, researchers noted that the condition impacts some racial and ethnic groups more than others: Black individuals have a 75 percent higher risk of developing prostate cancer than whites, and the disease is more than twice as deadly in black populations than it is among white people.

As is the case in many clinical trials, whites are often overrepresented as research participants in studies on prostate cancer – making it difficult to address and understand differences in disease risk and outcomes.

Current guidelines for prostate cancer screening suggest that those 55 and older with average risk can choose to take the prostate-specific antigen (PSA) test in consultation with their physicians. High PSA levels are associated with prostate cancer, but the PSA test tends to detect slow-growing tumors. The test often leads to unnecessary treatment with widespread use.

The research group noted that if the PSA tool were to be deployed selectively to monitor people found to be at high risk of prostate cancer, then its value would grow significantly. With refined genetic risk scores, this possibility could become a reality – and those with particularly high risk could begin screening before age 55.

Researchers at the University of Southern California (USC) Center for Genetic Epidemiology and the Institute of Cancer Research in London used genomic datasets from countries including the US, UK, Japan, Sweden, and Ghana to compare 107,247 men with prostate cancer to a control group made up of 127,006 men.

The team expected that examining a range of races and ethnicities would make genetic risk scores more useful for more people. The study is the largest, most diverse genetic analysis ever conducted for prostate cancer, and possibly for any other cancer.

The team 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.

Researchers then applied a model for assessing prostate cancer risk based on the interplay of these genetic factors, and found that men of African ancestry inherit about twice the prostate cancer risk on average compared to men of European ancestry. Men of Asian ancestry inherit about three-quarter the risk of white men.

These findings show that genetics play a role in the prevalence of cancer across certain groups, researchers noted.

“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 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.

“This emphasizes the value of adding multiple racial and ethnic populations into genetic studies.”

The study marks a momentous step in refining risk scores for prostate cancer and better understanding genetic risks of the disease.

“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 Haiman. “Men at higher risk may benefit from earlier and more frequent screening, so the disease can be identified when it’s more treatable.”

Additionally, the research advances scientists’ efforts to apply precision medicine to early detection of prostate cancer.

“The Prostate Cancer Foundation believes that Dr. Haiman’s research findings will lead to more effective prostate cancer precision screening strategies for men of West African ancestry,” said Jonathan W. Simons, MD, president and chief executive officer of the Prostate Cancer Foundation (PCF).

“PCF is certain that identification of these very high-risk individuals will make a positive impact on this significant health care disparity.”

To translate the research findings into better early detection, researchers noted that a large-scale, diverse clinical trial is necessary.

“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 findings of this study echo those of a separate report recently published in Clinical Cancer Research, in which researchers discovered significant differences between prostate cancer tumor cells in African American and European American men.

The results from the Clinical Cancer Research study also support the development of precision medicine treatments for prostate cancer.

“Currently there are only two immunotherapy options for prostate cancer patients: the sipuleucel-T cell vaccine and pembrolizumab. However, not everyone responds to those therapies,” said Kosi Yamoah, MD, PhD, associate member and director of cancer disparities research in the departments of Radiation Oncology and Cancer Epidemiology at Moffitt.

“Our study shows that African American men have higher overall immune content within their tumor microenvironment and higher expression of T lymphocytes. We can use that information to select a therapy that better targets their tumor and therefore improve their outcome.”