• J. Am. Coll. Surg. · Jan 2025

    Survival Disparity and the Unique Genomic and Microbiome Profiles of Colon Cancer in Appalachian Kentucky.

    • Hannah G McDonald, Anna M Reagan, Abu Saleh Mosa Faisal, Ryan Goettl, Chi Wang, Rebecca Hoyd, Daniel Spakowicz, B Mark Evers, Joseph Kim, and Avinash S Bhakta.
    • Department of Surgery, University of Kentucky Medical Center, Lexington, KY.
    • J. Am. Coll. Surg. 2025 Jan 27.

    BackgroundColon cancer is a leading cause of mortality in Appalachian Kentucky. Studies suggest that the microbiome may influence cancer outcomes. We investigate differential gene expression, the tumor microbiome, and the association between the two as potential drivers of disparities in colon cancer outcomes.Study DesignThis study analyzed patients diagnosed with colon adenocarcinoma between 2010-2023. Demographic data were extracted from Kentucky Cancer Registry. Somatic mutations and significantly mutated genes were identified using Fischer's exact T-test. RNASeq data was processed for gene expression analysis and Holm-Bonferroni method was used to adjust p-values for multiple comparisons. The STAR aligner, (exotic)v2.1 pipeline, and KrakenUniq database were used to classify microbes in human samples. The R package (exotic) was then used to decontaminate the results.ResultsThe final cohort included 2276 patients, 321 of which had available somatic mutation sequencing data. Demographic differences between Appalachian and non-Appalachian patients included marital status (P = 0.0005), race (P < 0.0001), insurance status, (P = 0.0005), BMI (P = 0.001), type 2 diabetes (P < 0.0001) and Charlson Comorbidity Index (CCI; P = 0.03). There was no difference in gene mutation frequency. There was differential expression of 228 genes. Differential abundance analysis revealed differences in 381 bacterial species. Importantly, 3 microbiota significantly correlated with survival disparities between Appalachian and non-Appalachian patients: C. cadaveris (adjusted P = 0.009), L. salivarius (adjusted P = 0.048), and S. wadsworthensis (adjusted P = 0.009).ConclusionThis is the first report of the distinct tumor microbiome in Appalachian Kentucky and its impact on survival. Further studies are needed to better characterize the unique tumor and gut microbiome of Appalachian patients with colon cancer.Copyright © 2025 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.

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