Biomarkers may predict risk for advanced prostate cancer among Black men
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Researchers have discovered a biological mechanism among men with diabetes and metastatic prostate cancer that they believe may lay the foundation for better testing and treatments for Black men with both diseases.
As many as one in three adults in the United States will have diabetes by 2050, according to CDC projections, and Black men are more than twice as likely than other men to die of prostate cancer.
“We really need to understand better ways to prevent people from developing and dying of these serious diseases,” Sarah Shuck, PhD, assistant professor in the Arthur Riggs Diabetes & Metabolism Institute and department of diabetes and cancer metabolism at City of Hope, told Healio.
Results of a small trial Shuck and colleagues conducted revealed four metabolism-related biomarkers associated with elevated risk for metastatic prostate cancer among men of West African heritage. Using a genetic technique pioneered by her collaborator Rick Kittles, PhD, the group accurately determined the percentage of West African ancestry amongst the trial participants.
Methylglyoxal — a metabolism byproduct that is elevated among individuals with diabetes — binds with RNA, DNA and protein to create a complex that may drive cancer growth, according to investigators.
The findings may help contribute to development of a tool to predict which Black men are at greatest risk for metastatic prostate cancer, said Shuck, who presented her team’s findings at the American Chemical Society Fall 2023 meeting.
Healio spoke with Shuck about efforts to better understand the finding and its implications, as well as how it will inform future research that one day may help better predict which Black men are at greatest risk for developing metastatic prostate cancer.
Healio: What motivated you to conduct this study?
Shuck: We were interested in understanding why people with diabetes have an increased risk for developing and dying of cancer. As we looked into this, we found African American men have a very high rate of diabetes compared with men of other ethnicities, and Black men with diabetes also have a higher risk for dying of prostate cancer than white men with diabetes. We wanted to investigate if we could develop tools that could predict which of these men were at the highest risk of dying of prostate cancer.
Healio: Can you briefly describe the findings? Did anything surprise you?
Shuck: We started the study by meeting with some of our colleagues at City of Hope — John Termini, PhD; Rick Kittles, PhD; and Leanne Woods-Burnham, PhD. Kittles and Woods-Burnham are now at Morehouse School of Medicine, but they had conducted a prior trial with banked clinical samples and extensive clinical data. We approached them and asked if they’d be interested in collaborating to see if we could observe differences in metabolic markers measured in our lab between Black and white men with and without prostate cancer.
We originally hypothesized that these circulating blood markers indicative of changes in metabolism would be elevated in Black men compared with white men. But when we did this study, we found the opposite. There were lower levels in African American men than white men, and that was very surprising.
We hypothesized that it could be associated with accumulation of these metabolic byproducts inside the tumor, leading to more growth and metastasis. Discussions with other colleagues revealed that this phenomenon may be present in other groups with cancer.
So, it’s not completely unusual to see lower circulating levels when we’re talking about tumor growth and metastasis. These are very unique molecules in that they not only may predict disease risk but potentially drive disease, as well.
Healio: What do you consider the most important clinical implication of these findings?
Shuck: In addition to our measurements of metabolic markers, we also looked at proteins and genetic markers that also are associated with metabolic changes. Each component that we looked at revealed differences between Black and white men, and these are all components of changes in metabolism that are associated with diabetes. We think developing this comprehensive panel of biomarkers might have utility for predicting risk for dying of prostate cancer.
Healio: What are the next steps in research, and what key questions must answered?
Shuck: Our next step is to validate these findings in an additional cohort. We are working to find a cohort that not only has the blood samples as described in this trial, but also prostate cancer biopsies. This will allow us to further test our hypothesis that lower circulating blood levels of metabolic markers are associated with higher accumulation in prostate tumors. The next step will be to use mouse models to understand more about the biochemistry and turnover of these molecules inside the body. We’ll take prostate cancer cells derived from either Black men or white men and put them into mice. We want to determine if we expose them to conditions like you’d have in diabetes, does it drive metastatic prostate cancer growth and can these molecules be measured in mice to determine risk for that growth?
Healio: What is the potential impact if these findings are validated?
Shuck: Our long-term goal is to be able to incorporate this into a clinical chemistry test, so using the types of methods that are used in clinical chemistry labs — like mass spectrometry — to be able to measure these molecules from patients in tandem or independently of current biomarkers.
Our short-term goal is to understand the mechanisms by which diabetes increases the risk for dying of prostate cancer. So, in addition to looking at these biomarkers and trying to understand these mechanisms, it may help us better understand how to use precision medicine approaches and why people may respond to certain therapies better than others. It also can allow us to think about ways to screen large populations in a different way.
We hope we can use the information we’re learning about how diabetes drives disease to explore novel ways that we can treat and prevent prostate cancer in diverse populations.
F or more information:
Sarah Shuck, PhD, can be reached at sshuck@coh.org.
References:
- City of Hope researchers identify biomarkers that may detect risk of advance prostate cancer in Black men (press release). Available at: https://www.cityofhope.org/city-hope-researchers-identify-biomarkers-may-detect-risk-advance-prostate-cancer-black-men. Published Aug. 15, 2023. Accessed Aug. 22, 2023.
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