September 19, 2022
Contact: Thonnia Lee, Office of Communications, Public Relations and Marketing
Tuskegee University researchers have discovered that certain genetic variants found in prostate tumors in men of African descent have been linked to African ancestry, according to two studies led by Dr. Clayton Yates, professor of biology and director of the Multidisciplinary Center for Biomedical Research and graduate student Isra Elhussin University.
Both studies, supported by the US Department of Defense and the National Institutes of Health’s National Cancer Institute, highlight the contributions of African ancestry to prostate cancer genetics and provide a resource to address cancer health disparities. The studies were presented during the 15th AACR Conference on the Science of Cancer Health Disparities in Racial and Ethnic Minority and Medically Underserved People in Philadelphia, Pennsylvania.
Inherited genetic factors
“In the United States, black men have the highest mortality rate related to prostate cancer. Most studies examining differences focus on race, which is usually self-reported and defined by skin color and social and cultural characteristics,” said Dr. Yates, who is also senior author of both studies and chair of the AACR Minorities in Cancer Research Council.
dr Yates said that tackling health inequalities requires understanding the contributions of genetic lineage to tumor biology. Insights into genetic ancestry could aid precision medicine efforts by uncovering potential therapeutic targets specific to patients of African descent.
In the first study, Isra Elhussin, an AACR NextGen Star, examined the influence of African descent on the expression of immunoinflammatory gene signatures associated with higher immunogenicity and aggressive prostate cancer in African descent men. Elhussin and other project collaborators reported that prostate tumors from African-American men had two-fold greater activation of inflammatory signals, which could contribute to the more aggressive disease typically seen in these patients.
“Cancer is one of the leading causes of death in the black community. Access to health care, socioeconomic status and genetic ancestry are directly related to differences in survival,” Elhussin said. “The under-representation of black patients in genomic studies and clinical trials impacts precisely their usefulness in personalized medicine.”
“Our research underscores the need for diversity in cancer research to bridge the gap and build trust in our black community,” Elhussin said. “We are focusing on strategies that could aid in disease prevention and therapeutic intervention by linking cancer genes back to their ancestral origin and stratifying lineage-specific markers that influence patient outcomes and their response to targeted therapy.”
investigation of possibility
Elhussin and colleagues sequenced prostate tumors from 72 patients in the United States who had not undergone cancer treatment to determine the role of African ancestry in prostate cancer. Using reference databases, Elhussin found that most patients who identified as African American had genetic markers consistent with males of African descent.
“We are the first to show that African genetic ancestry is associated with a SPOP mutation that results in higher immunogenicity, upregulation of an immune system inflammatory signature, and greater tumor infiltration of immune cells expressing markers of exhaustion, suggesting a potential mechanism.” for the higher prostate cancer-related mortality in men of African descent,” said Elhussin. “These findings have implications for the treatment of prostate cancer and could lead to new therapeutic strategies that use anti-inflammatory drugs and immunomodulators to reduce the burden of the disease in men of African descent to reduce parentage.”
“This is an exciting discovery that could help identify patients who would benefit from immunotherapy, which is particularly important since African Americans are often underrepresented in clinical trials evaluating such therapies,” Yates noted.
The second study was published in the American Association for Cancer Research (AACR) journal Cancer Research Communities; Yates, along with colleague Jason White, MS, compared DNA sequences from Nigerian, African-American, and Caucasian-American patients with prostate cancer. The study was conducted in collaboration with the Prostate Cancer Transatlantic Consortium (CaPTC).
“Our goal was to understand the genomic contributions to prostate cancer in Nigerian men, something that had never been studied before,” said Dr. Yates. “We performed sequencing to determine if there are unique mutations associated with the Nigerian population that differ from those found in tumors of African Americans or European Americans and to identify similarities between these populations.”
The research found that genetic variants were similar between Nigerian and African-American prostate cancer, with specific variants in certain genes.
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