Colon Cancer in Appalachian Kentucky: Unique Genetic, Microbiome and Obesity Findings in a Cohort Comparison.

IF 3.6 Q2 GENETICS & HEREDITY

HGG Advances Pub Date : 2025-10-07 DOI:10.1016/j.xhgg.2025.100527

Zeta Chow, Jinpeng Liu, Daheng He, Chi Wang, Tong Gan, Akila Mansour, Nuha Shaker, Caroline Dravillas, Rebecca Hoyd, Eric Durbin, Dana Napier, Tianyan Gao, Kurt Schaberg, Lyen Huang, Neli Ulrich, Erin Siegel, Stephen Edge, Linda Cook, Bodour Salhia, Michelle Churchman, Jill Kolesar, Daniel Spakowicz, B Mark Evers, Therese Bocklage

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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.

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肯塔基州阿巴拉契亚地区的结肠癌：队列比较中独特的遗传、微生物组和肥胖发现。

我们研究了美国结肠癌发病率最高的阿巴拉契亚肯塔基州人群的结肠癌基因组学和微环境特征。我们评估了这一人群中结肠癌的两个相互关联的危险因素（肥胖和肠道细菌微生物群异常）及其遗传关联。为了评估高发病率队列的潜在独特特征，我们比较了来自肯塔基州阿巴拉契亚地区的99例倾向匹配的结肠癌肿瘤患者和95例非阿巴拉契亚患者肿瘤，以评估肥胖背景下的驱动突变、差异表达基因（DEGs）、京都基因和基因组百科全书（KEGG）途径、癌症体细胞突变目录（COSMIC）突变特征、免疫细胞群和微生物组。我们的比较发现了显著的人群特异性deg和COSMIC信号频率、KEGG通路调节、前致癌免疫细胞特征、微生物组物种以及肥胖相关炎症和代谢反应的差异。该研究结果提供了来自阿巴拉契亚肯塔基州的普遍意义，同时强调了以人群为基础的研究在结肠癌研究中的重要性。

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