For decades, Black American patients have had a higher incidence and higher mortality of laryngeal cancer than patients of other races, particularly Black men. The disparity appears even when accounting for sociodemographic factors like income, insurance status or education.
“The gap is tremendous and the fact that it has persisted over so many years and decades is disconcerting,” said UF Health Cancer Institute member Kristianna Fredenburg, M.D., Ph.D., an assistant professor in the UF Department of Pathology, Immunology and Laboratory Medicine. “Our research is focused on understanding the contribution of biology to this cancer health disparity.”
At the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego, Fredenburg’s lab presented evidence of differences in gene regulation based on ancestry. The findings could inform more precise treatments by identifying genes to be targeted with drugs and predicting how patients will respond to cancer treatment.
In one study, Fredenburg’s team investigated ancestral differences in microRNAs, small molecules that regulate gene expression. A type of microRNA called microRNA-9 is lower in laryngeal cancer patients with African ancestry than in those with European ancestry. The researchers wanted to find out whether ancestral differences in microRNA binding partners and cancer genetic pathways could explain the differences in clinical outcomes.
The researchers, led by UF graduate student Chayil Lattimore, gathered gene expression data from patients in The Cancer Genome Atlas, a landmark cancer genomics program run by the National Cancer Institute and National Human Genome Research Institute.
Next, the team used a novel method, called chimeric enhanced cross-linking and immunoprecipitation (eCLIP), to analyze RNA interactions in laryngeal cancer cell lines. It’s the first time the tool has been used to investigate ancestral differences in cancer outcomes.
The study found that 70% of microRNA-targeted pathways were shared between African and European ancestry groups, but a certain population of microRNA targets, including those related to cell adhesion and MAPK regulation, were associated primarily with African ancestry.
“We identified some unique pathways associated with ancestry,” Fredenburg said. “We think this method could be applied to understanding unique ancestral pathway differences in other cancer types and could offer opportunities for precision treatments.”
Lattimore, the study’s first author, presented the study at AACR. UF Health Cancer Institute members Rolf Renne, Ph.D., and Mingyi Xie, Ph.D., are co-authors.
In another study presented at AACR, Fredenburg’s team investigated whether a protein called ABCC1 could serve as a prognostic biomarker for laryngeal cancer health outcomes. Because the protein pumps drugs out of cells, overexpression of ABCC1 is associated with worse overall survival in several types of cancer and worse responses to chemotherapy.
The researchers collected tumor tissue from 92 patients with advanced-stage laryngeal squamous cell carcinoma from African or European heritages. They stained the tumors for ABBC1 protein expression, then used machine learning and artificial intelligence to train a software to score the expression.
“AI allowed us to have an objective way to quantify protein expression by giving a numerical score to each tumor,” Fredenburg said.
This work confirmed the researchers’ preliminary findings that Black patients have higher ABCC1 levels than White patients.
The researchers also found that high ABCC1 levels were associated with a lower risk of cancer recurrence regardless of other factors like race. However, Black patients had a higher risk of cancer recurrence than White patients, even when controlling for ABCC1 expression and other factors.
“Even though Black patients are more likely to have high ABCC1 levels, the fact that race is an independent predictor means Black patients may not have a protective effect from their high ABCC1 expression,” Fredenburg said.
Christina Gobin, Ph.D., a clinical research manager in Fredenburg’s lab, is the study’s first author and presented the study at AACR.
The team plans to further research the effects of differences in gene expression on cancer outcomes and how this can inform treatment for patients in the context of ancestry. Both studies were funded by the Department of Defense.
