Colon cancer in Appalachian Kentucky: Unique genetic, microbiome and obesity findings in a cohort comparison
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.
Authors
- Akila Mansour
- Thèrése Bocklage (ORCID: https://orcid.org/0000-0003-0899-9405)
- Neli Ulrich
- Stephen B. Edge (ORCID: https://orcid.org/0000-0002-3285-6191)
- Dana Napier
- Rebecca Hoyd (ORCID: https://orcid.org/0000-0003-1210-4491)
- Linda Cook (ORCID: https://orcid.org/0000-0002-2049-6598)
- Bodour Salhia
- Daniel Spakowicz (ORCID: https://orcid.org/0000-0003-2314-6435)
- Lyen C. Huang (ORCID: https://orcid.org/0000-0002-8605-2631)
- Eric B. Durbin (ORCID: https://orcid.org/0000-0002-5600-7645)
- Michelle L. Churchman (ORCID: https://orcid.org/0000-0002-6560-1056)
- Jill Kolesar
- Nuha Shaker (ORCID: https://orcid.org/0000-0002-7540-6916)
- B. Mark Evers (ORCID: https://orcid.org/0000-0002-9425-2342)
- Erin M. Siegel (ORCID: https://orcid.org/0000-0003-1779-2510)
- Kurt B. Schaberg
- Daheng He (ORCID: https://orcid.org/0000-0003-0399-2466)
- Caroline E. Wheeler (ORCID: https://orcid.org/0000-0002-3374-4909)
- Tianyan Gao (ORCID: https://orcid.org/0000-0003-1159-3625)
- Chi Wang (ORCID: https://orcid.org/0000-0001-8984-4995)
- Jinpeng Liu (ORCID: https://orcid.org/0000-0003-4100-0237)
- Tong J. Gan (ORCID: https://orcid.org/0000-0001-5506-398X)
- Zeta Chow
Institutions
- Roswell Park Comprehensive Cancer Center (US)
- University of Kentucky (US)
- University of Pittsburgh (US)
- University of Utah (US)
- Huntsman Cancer Institute (US)
- Markey Cancer Center (US)
- University of Colorado Cancer Center (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Human Genetics and Genomics Advances
- Published
- 2025-10-10
- DOI
- https://doi.org/10.1016/j.xhgg.2025.100527
- Primary Topic
- Colorectal Cancer Screening and Detection
- Type
- article
- Field-Weighted Citation Impact
- 0.00