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Discovering Population-Specific Epigenetic Markers for Pancreatic Cancer Through Examination of Chromatin Accessibility

April 20, 2022
by Krupa Sekhar
Krupa Sekhar

Abstract: Cancer plagues the human population disparately across race and sex, yet research is severely lacking in discovering biological contributors to lopsided incidence and mortality. While past studies have focused on genetic mutations, this study is the first to combine epigenetic analysis with pancreatic cancer (PC) population oncology to investigate poorly understood male and African American (AA)-specific PC incidence-- male vs female PC incidence is 5.5 per 100,000 vs 4.0 per 100,000, and AAs have up to 90% higher incidence than white patients. Data obtained from an Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) study was computationally analyzed, and variable chromatin accessibility was demonstrated (p<.05). Y Chromosome differential accessibility analyses were subsequently performed, and significant accessibility increases were apparent in the progression to malignant tissue (p<.05), indicating an epigenetic role in increased male PC incidence. A racial analysis was then performed via KEGG pathway analysis, and driver genes of PC were found to be correlated with significantly variable methylation in AAs. This research discovered epigenetic variability correlated with 41 gene families that may contribute to higher male and AA-specific PC incidence. The discovered PC contributors can be further investigated to develop targeted therapies and population-specific screening methods, and this research methodology can be used to uncover similar contributors to population disparities in other diseases.  

Keywords:  pancreatic cancer (PC), population oncology, African American (AA)-specific PC incidence, racial analysis, KEGG pathway analysis

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