TU researchers link a genetic origin to prostate tumors

September 19, 2022

Contact: Thonia Lee, Office of Communications, Public Relations and Marketing

Dr..  Clayton Yates and Esraa Al Hussein
Yeats and Hussein

Researchers at Tuskegee University have discovered specific genetic variants found in prostate tumors in men of African descent that are linked to African ancestry, according to two studies led by Dr. Student Esraa Al-Hussein.

Both studies, supported by the US 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, Ethnic, and Medically Disadvantaged Minorities held in Philadelphia, Pennsylvania.

Inherited genetic factors

“In the United States, black men have the highest rate of deaths related to prostate cancer,” said Dr. Yates. “Most studies examining disparities focus on race, and it is usually self-reported and defined by skin color and sociocultural traits.” He serves as lead author on both studies, and chair of the AACR Minorities at the Cancer Research Council.

Addressing health disparities requires understanding the contributions of genetic lineage to tumor biology, Dr. Yates said. Insights into genetics could aid precision medicine efforts by revealing potential therapeutic targets for patients of African descent.

In the first study, AACR NextGen Star Esraa El-Hussein examined the effect of African ancestry on the expression of immune-mediated inflammation-related genetic signatures and aggressive prostate cancers in men of African descent. Al-Hussein and other colleagues on the project reported that prostate tumors from African American men have a multiplicative activation of inflammatory signals, which may contribute to the more aggressive disease typically observed in these patients.

“Cancer is one of the leading causes of death in the black community,” Al-Hussein said. “Access to health care, socioeconomic status, and genetic ancestry are directly related to differences in survival.” “The underrepresentation of black patients in genetic studies and clinical trials precisely influences their benefits from personalized medicine.”

“Our research highlights the need for diversity in cancer research, bridging the gap and building trust with our black community,” Al-Hussein said. “We are focusing on strategies that can aid disease prevention and therapeutic intervention by linking cancer genes back to their ancestral origin and stratifying ancestral markers that influence patient outcomes and response to targeted therapy.”

Investigate the possibility

Al-Hussein and colleagues sequenced prostate tumors from 72 patients in the United States who had not had cancer treatment to determine the role of African ancestry in prostate cancer. Using reference databases, Al-Hussein determined that most patients identified as African American had genetic markers consistent with men of African descent.

“We are the first to show that the African genetic lineage is associated with a SPOP mutation, which leads to increased immunity, regulation of the immune inflammatory signature, and tumor infiltration of immune cells expressing markers of fatigue, providing a potential mechanism for higher prostate cancer–mortality in African men.” “These findings have implications for prostate cancer treatment and could lead to new treatment strategies using anti-inflammatory drugs and immunomodulators to reduce disease burden among men of African descent.”

“This is an exciting finding that may help identify patients who may benefit from immunotherapy, which is particularly important because African Americans are often underrepresented in clinical trials evaluating such treatments,” Yates noted.

The second study was published in the American Association for Cancer Research (AACR) in the Journal of the Cancer Research Society. Yates, along with colleague Jason White, compared the DNA sequences of Nigerian, African American and European prostate tumor patients. The study was completed in collaboration with the Transatlantic Prostate Cancer Consortium (CaPTC).

“Our goal was to understand the genetic contributions of prostate cancer among Nigerian men, something that had not been studied before,” said Dr. Yates. “We performed sequencing to determine if there were unique mutations associated with the Nigerian population that differed from those in tumors from African Americans or European Americans, as well as to identify any similarities between these populations.”

The research found that genetic variants were similar between Nigerian and African American prostate tumors, with specific variants in certain genes.

© Tuskegee University 2022

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