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Researchers at Tuskegee University have discovered specific genetic variants found in prostate tumors of men of African descent were associated with African ancestry, according to two studies led by Dr. Clayton Yates, professor of biology and director of the university's multidisciplinary Center for Biomedical Research and graduate student Isra Elhussin.
Both studies supported by the United States Department of Defense and the National Cancer Institute of the National Institutes of Health highlight the contributions of African ancestry to prostate cancer genetics and provide a resource for addressing cancer health disparities. The studies were presented during the 15th AACR Conference on the Science of Cancer Health Disparities in Racial and Ethnic Minorities and the Medically Underserved held in Philadelphia, Pennsylvania.
Inherited Genetic Factors
"In the United States, Black men have the highest rate of prostate cancer-related mortality. Most studies examining disparities focus on race, typically self-reported and defined by skin color and social and cultural traits," said Dr. Yates, who also serves as the senior author on both studies, and chair of the AACR Minorities in Cancer Research Council.
Dr. Yates said addressing health disparities requires understanding genetic ancestry's contributions to tumor biology. Insights into genetic ancestry could aid precision medicine efforts by uncovering potential therapeutic targets specific to patients with African ancestry.
In the first study, Isra Elhussin, an AACR NextGen Star, examined the impact of African ancestry on the expression of immune inflammation gene signatures associated with higher immunogenicity and aggressive prostate cancers in men of African descent. Elhussin and other project colleagues reported that prostate tumors from African American men had a twofold greater activation of inflammatory signaling, which may contribute to the more aggressive disease typically observed in these patients.
"Cancer is one of the primary leading causes of death in the Black community. Access to healthcare, socioeconomic status, and genetic ancestry are directly correlated to survival disparities," said Elhussin. "The underrepresentation of Black patients in genomic studies and clinical trials precisely impacts their benefits of personalized medicine."
" Our research highlights the need for diversity in cancer research, filling the gap and building trust with our Black community," said Elhussin. "We are focusing on strategies that could help with disease prevention and therapeutic intervention by linking cancer genes back to their Ancestral origin and stratifying Ancestry-specific markers that affect patients' outcomes and their response to targeted therapy."
Investigating the 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 determined that most of the patients who identified as African American had genetic markers consistent with men of African descent.
"We are the first to demonstrate that African genetic ancestry is associated with SPOP mutation, which leads to higher immunogenicity, upregulation of an immune inflammation signature, and higher tumor infiltration of immune cells expressing exhaustion markers, providing a potential mechanism for the higher prostate cancer-related mortality among men with African ancestry," said Elhussin. "These findings have implications for treating prostate cancers and could lead to new therapeutic strategies using anti-inflammatory drugs and immune modulators to decrease the disease burden among men of African descent."
"This is an exciting discovery that may help identify patients who would benefit from immunotherapy, which is particularly important given that African Americans are often underrepresented in clinical trials evaluating such therapies," noted Yates.
The second study was published in the American Association for Cancer Research (AACR) in the journal Cancer Research Communities; Yates, alongside colleague Jason White, MS, compared DNA sequences from Nigerian, African American, and European American prostate tumor patients. The study was completed in collaboration with the Prostate Cancer Transatlantic Consortium (CaPTC).
"Our goal was to understand the genomic contributions to prostate cancer among Nigerian men, something that had never been studied before," said Dr. Yates. "We performed sequencing to determine if there were unique mutations associated with the Nigerian population that was distinct from those in tumors from African Americans or European Americans, as well as to identify any similarities across these populations."
The research found that genetic variants were similar between the Nigerian and African American prostate tumors, with specific variants in particular genes.
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