Researchers have identified a cell metabolism process found in male patients with West African ancestry who have diabetes and metastatic prostate cancer that could potentially lead to improved testing and treatments for Black patients with both diseases. The findings by Shuck et al were presented at the American Chemical Society Fall 2023 meeting.
Background
Black patients are 60% more likely than White patients to be diagnosed with diabetes and twice as likely to die from the disease. The American Cancer Society reported that Black patients are also 70% more likely to be diagnosed with prostate cancer and two to four times as likely to die from the disease compared with other racial and ethnic groups.
The researchers stressed that the highly reactive compound methylglyoxal, a byproduct of metabolism that is elevated in patients with diabetes, may be responsible for the heightened risk of prostate cancer. Methylglyoxal binds to DNA, RNA, and protein—creating a complex that may promote cancer emergence as a result of its instability and disrupted function.
Study Methods and Results
In the new study, the researchers sought to better understand the intersection between cancer and diabetes. They identified four new metabolism-related biomarkers that may be linked to an increased risk of metastatic prostate cancer in male patients with West African ancestry.
“We have identified genetic and molecular changes that can be developed into a tool to predict which Black [patients] are at the highest risk of developing metastatic prostate cancer,” said senior study author Sarah Shuck, PhD, Assistant Professor in the Department of Diabetes & Cancer Metabolism at the Arthur Riggs Diabetes & Metabolism Institute at the City of Hope.
In previous studies, Dr. Shuck and her colleagues have investigated how metabolic dysregulation could cause diabetes and cancer as well as the biochemistry involved when excess sugar damages important molecules. To see if the identified dysregulated complexes were linked to race and genetics, the researchers gathered blood samples from 371 patients with and without prostate cancer and determined their race by assessing the samples for genetic evidence of West African ancestry. They then analyzed the four new biomarkers associated with methylglyoxal—including variation in the GLO1 gene—and the complexes it formed with DNA, RNA, and protein.
The researchers discovered that male patients with West African ancestry had fewer malignancy-promoting complexes in their blood and that a lower level of these complexes was linked to a greater risk of metastatic prostate cancer.
Conclusions
The researchers hypothesized that in male patients with West African ancestry, tumor cells may sequester these complexes and spur metastatic processes from within. However, their findings did not apply to male patients with European ancestry. The researchers further suggested that metylglyoxal advanced glycation end products, soluble RAGE, the GLO1 gene, and AGER gene single-nucleotide polymorphisms may be used as biomarkers for prostate cancer in Black patients and that the variation GLO1 may play a role in the accumulation of mutations that lead to prostate cancer cell growth.
“This test would give [physicians] the ability to more accurately predict patients’ prognoses and equip [researchers] with more data as they work to design therapies that prevent prostate cancer from developing in the first place,” Dr. Shuck emphasized.
The researchers plan to further evaluate prostate cancer disparities in the hopes of developing more inclusive diagnostic and predictive tests and personalized treatments for Black patients.
