Abstract 6516: Comparative microbiome analysis of tumor and normal colorectal tissue across diverse racial and ethnic groups

Background: Disparities in colorectal cancer (CRC) incidence and outcomes are notable between racial and ethnic groups. While these differences may be associated with various factors, established risk factors do not fully explain observed disparities. Increasingly, evidence suggests that the microbiota associated with the tumor microenvironment may play a role in CRC initiation and/or progression. However, few studies have investigated the microbiome of CRC tumor tissue compared to the microbiome in paired normal tissue as a reference. This study explores the microbial landscape of tumor and normal colorectal tissues from diverse racial and ethnic patients with CRC to understand the microbiome’s potential role in CRC disparities. Methods: We conducted bacterial 16S rRNA gene sequencing of colorectal tumor and normal tissue from 283 individuals of varied racial and ethnic backgrounds (African American, Alaska Native, Hispanic, and Non-Hispanic White). We extracted genomic DNA from tumor and normal colon tissue. We used amplicon sequencing of the 16S rRNA gene to classify the relative abundance of different bacterial amplicon sequence variants (ASVs), genera, and phyla in colon tissue. 8 phyla and 48 genera were identified across all samples. We used linear mixed models to identify differences in alpha diversity (assessed as Shannon diversity) between tumor and normal tissue in all participants combined, as well as within each racial and ethnic group. Linear mixed models were also used to identify associations of specific genera with the tumor and normal tissues. All models were adjusted for sex, race, age, ethnicity, tumor stage, tumor site, and year of diagnosis. Results: Our analysis identified significant differences in microbial composition and diversity between normal and tumor tissue. Alpha diversity of the microbiota was significantly lower in tumor tissue compared with normal tissues when all racial and ethnic participants were combined (p < 0.001). There were also significant differences in alpha diversity between normal and tumor tissue within different racial and ethnic populations (p < 0.05) as well as within tumor tissue between different racial and ethnic populations (p < 0.05). After accounting for multiple testing, several genera were found to have a lower relative abundance in tumor tissue compared to normal tissue (p < 0.05). These included Bacteroides, Parabacteroides, Ruminococcus, Faecalibacterium, and other genera. Conclusion: This study enhances our understanding of the CRC-related microbiome. By detailing the diversity and abundance profiles of microbial communities in tumor microenvironments versus normal tissues, we identified differences in the distribution and composition of the microbiome in tumor versus normal tissue, as well as identified specific bacterial genera that were found to have a lower relative abundance in tumor tissues. Citation Format: Scott D. Labrie, Claire E. Thomas, Nicole Loroña, Keith R. Curtis, Hang Yin, Timothy W. Randolph, Ningxin Ma, Jeroen R. Huyghe, Sushma S. Thomas, Li Hsu, Amanda L. Koehne, Sosun Nayemi, Orsalem J. Kahsai, Jane C. Figueiredo, Li Li, Diana G. Redwood, Timothy Thomas, Christopher I. Li, Amanda I. Phipps, Ulrike Peters, Meredith Hullar. Comparative microbiome analysis of tumor and normal colorectal tissue across diverse racial and ethnic groups [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6516.