Abstract
We investigated colon cancer genomics and microenvironmental features in the Appalachian Kentucky population, a group with the highest incidence of colon cancer in the United States. We assessed two inter-related risk factors for colon cancer (obesity and abnormal gut bacterial microbiome) and their genetic associations within this population. To evaluate potential unique characteristics of the high-incidence cohort, we compared 99 propensity-matched colon cancer tumors from Appalachian Kentucky patients to 95 non-Appalachian patient tumors to evaluate driver mutations, differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, immune cell populations, and microbiomes in an obesity context. Our comparison identified significant population-specific DEGs and differences in COSMIC signature frequencies, KEGG pathway regulation, pro-carcinogenic immune cell features, microbiome species, and obesity-associated inflammatory and metabolic responses between the cohorts. The findings offer generalizable implications deriving from Appalachian Kentuckians while highlighting the critical importance of population-based studies in colon cancer research.
Document Type
Article
Publication Date
2026
Digital Object Identifier (DOI)
https://doi.org/10.1016/j.xhgg.2025.100527
Funding Information
The Markey Cancer Center’s Research Communications Office assisted with manuscript preparation. This research was supported by the Cancer Research Informatics, Biostatistics and Bioinformatics, and Biospecimen Procurement and Translational Pathology Shared Resources of the University of Kentucky Markey Cancer Center (P30 CA177558). The ORIEN TCC (Tampa, FL) provided whole-genome sequencing and RNA-seq for the AplT tissue and existing data for participating non-Appalachian patients in this study.
Repository Citation
Chow, Zeta; Liu, Jinpeng; He, Daheng; Wang, Chi; Gan, Tong; Mansour, Akila; Shaker, Nuha; Dravillas, Caroline; Hoyd, Rebecca; Durbin, Eric B.; Napier, Dana L.; Gao, Tianyan; Schaberg, Kurt; Huang, Lyen; Ulrich, Neli; Siegel, Erin; Edge, Stephen; Cook, Linda; Salhia, Bodour; Churchman, Michelle L.; Kolesar, Jill; Spakowicz, Daniel; Evers, B. Mark; and Bocklage, Therese J., "Colon cancer in Appalachian Kentucky: Unique genetic, microbiome and obesity findings in a cohort comparison" (2026). Markey Cancer Center Faculty Publications. 465.
https://uknowledge.uky.edu/markey_facpub/465
Notes/Citation Information
© 2025 The Author(s). Published by Elsevier Inc. on behalf of American Society of Human Genetics. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).