Abstract 1022: Tumor-associated microbiome association with colorectal cancer-specific mortality in a racially and ethnic diverse patient population
Authors: Claire E. Thomas, Nicole C. Loroña, Scott D. LaBrie, Keith R. Curtis, Hang Yin, Ningxin Ma, Timothy Randolph, Conghui Qu, Jeroen Huyghe, Sushma Thomas, Li Hsu, Amanda L. Koehne, Sosun Nayemi, Hamza Ammar, Orsalem Kahsai, Diana Redwood, Christopher I. Li, Li Li, Ulrike Peters, Jane C. Figueiredo, Timothy K. Thomas, Amanda I. Phipps, Meredith A. Hullar
Journal: Cancer Research (2025)

Abstract Background: The tumor-associated microbiome is an important component of the tumor microenvironment implicated in colorectal cancer (CRC) prognosis. However, it remains unclear which phyla or genera are associated with CRC-specific mortality, particularly in understudied racial and ethnic patient populations. Methods: We included 382 patients with CRC (90 African American, 95 Alaska Native, 71 Hispanic, and 126 non-Hispanic White) from the Translational Research Program in Colorectal Cancer Disparities (TRPCD). We conducted V4 16S rRNA gene sequencing of genomic DNA extracted from formalin-fixed paraffin embedded (FFPE) tumor tissue. Sequences were processed bioinformatically in QIIME 2.0 to classify the relative abundance of different bacterial genera and phyla in tumor tissue. All batches include positive, no template and tumor sample block wax controls that are extracted and sequenced and from which contaminants are identified and removed via bioinformatics. Patients who died of CRC were matched to patients who did not die of CRC by age, sex, tumor site, tumor stage, year at diagnosis, and racial and ethnic group. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between positivity (non-zero/zero) of phyla or genera with CRC-specific mortality, adjusted for all matching factors. As a sensitivity analysis, we also examined associations comparing those with high levels of a phyla or genera (among those non-zero, at or above the median) versus those with no such bacteria detected, or zero. Results: After 16S rRNA gene sequencing, 8 phyla and 48 genera were available for analysis. No phyla or genera were statistically significantly associated with CRC-specific mortality status after accounting for multiple testing. The strongest associations were for the genera Enterococcus, where positivity was inversely associated with CRC-specific mortality [OR positive versus zero (95% CI) = 0.52 (0.30, 0.87)], and the genera Cloacibacterium, where positivity was associated with greater odds of CRC-specific mortality [OR positive versus zero (95% CI) = 2.40 (1.14, 5.16)]. Comparing high levels to zero, the strongest association was for the genera Leptotrichia, where high levels were associated with greater odds of CRC-specific mortality [OR high versus zero (95% CI) = 2.60 (1.24, 5.54)]. Conclusions: While no phyla or genera were statistically significantly associated with CRC-specific mortality after accounting for multiple testing, there are several genera that have strong associations and warrant further investigation. This work may be useful identifying pathogens or protective agents that impact CRC-specific mortality in understudied populations. Citation Format: Claire E. Thomas, Nicole C. Loroña, Scott D. LaBrie, Keith R. Curtis, Hang Yin, Ningxin Ma, Timothy Randolph, Conghui Qu, Jeroen Huyghe, Sushma Thomas, Li Hsu, Amanda L. Koehne, Sosun Nayemi, Hamza Ammar, Orsalem Kahsai, Diana Redwood, Christopher I. Li, Li Li, Ulrike Peters, Jane C. Figueiredo, Timothy K. Thomas, Amanda I. Phipps, Meredith A. Hullar. Tumor-associated microbiome association with colorectal cancer-specific mortality in a racially and ethnic diverse patient population [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 1022.