Journal article
Colon Cancer in Appalachian Kentucky: Unique Genetic, Microbiome and Obesity Findings in a Cohort Comparison
HGG advances, Vol.7(1), 100527
01/15/2026
DOI: 10.1016/j.xhgg.2025.100527
PMCID: PMC12554973
PMID: 41063459
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.
Details
- Title: Subtitle
- Colon Cancer in Appalachian Kentucky: Unique Genetic, Microbiome and Obesity Findings in a Cohort Comparison
- Creators
- Zeta Chow - Markey Cancer CenterJinpeng Liu - University of KentuckyDaheng He - University of KentuckyChi Wang - University of KentuckyTong Gan - 5675 Treebrook Dr. NE, Ada, MI, 49301 USAAkila Mansour - University of PittsburghNuha Shaker - University of PittsburghCaroline Dravillas - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research InstituteRebecca Hoyd - The Ohio State UniversityEric Durbin - University of KentuckyDana Napier - University of KentuckyTianyan Gao - Markey Cancer CenterKurt Schaberg - California State University, SacramentoLyen Huang - Huntsman Cancer InstituteNeli Ulrich - University of UtahErin Siegel - Moffitt Cancer CenterStephen Edge - Roswell Park Comprehensive Cancer CenterLinda Cook - University of Colorado Cancer CenterBodour Salhia - University of Southern CaliforniaMichelle Churchman - Aster Insights, PO Box 5519, Hudson, FL 34667 USAJill Kolesar - University of KentuckyDaniel Spakowicz - The Ohio State UniversityB Mark Evers - University of KentuckyTherese Bocklage - University of Kentucky
- Resource Type
- Journal article
- Publication Details
- HGG advances, Vol.7(1), 100527
- DOI
- 10.1016/j.xhgg.2025.100527
- PMID
- 41063459
- PMCID
- PMC12554973
- NLM abbreviation
- HGG Adv
- ISSN
- 2666-2477
- eISSN
- 2666-2477
- Publisher
- Elsevier
- Grant note
- 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 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.
- Language
- English
- Electronic publication date
- 10/07/2025
- Date published
- 01/15/2026
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics; Obstetrics and Gynecology
- Record Identifier
- 9985014869402771
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