The Phylum Fusobacteriota Is Associated with Colorectal Cancer–Specific Mortality: Results from the Translational Research Program in Cancer Differences across Populations

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BACKGROUND: The microbiome is an important component of the tumor microenvironment implicated in colorectal cancer. However, its relationship with colorectal cancer-specific mortality remains unclear. METHODS: We included 581 participants with colorectal cancer (167 African American, 176 Alaska Native, 118 Hispanic, and 120 non-Hispanic White) from the Translational Research Program in Cancer Differences across Populations (TRPCDP). We sequenced the V4 region of the 16S rRNA bacterial gene using DNA extracted from formalin-fixed, paraffin-embedded tumors. A total of 204 participants died of colorectal cancer and 377 did not die of colorectal cancer. Participants who died of colorectal cancer were matched to participants who did not die of colorectal cancer during follow-up by age, sex, tumor site, tumor stage, year of diagnosis, and population group. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between bacterial presence and colorectal cancer-specific mortality, adjusting for matching factors and tissue macrodissection status. RESULTS: Individuals who died from colorectal cancer were 1.71 times as likely to have bacteria from the Fusobacteriota phylum present in their tumors (OR = 1.71; 95% CI = 1.19-2.47). Associations with Fusobacteriota were strongest among African American participants (OR = 2.36; 95% CI = 1.14-4.99) compared with other populations; however, this difference was not statistically significant (OR range = 1.05-1.38; Pinteraction = 0.697). Candidate pathways of pyruvate fermentation to acetate and lactate II and peptidoglycan biosynthesis I were associated with higher odds of colorectal cancer death. CONCLUSIONS: Fusobacteriota was significantly associated with colorectal cancer-specific mortality with noted differences across populations. IMPACT: This finding highlights the tumor microbiome as a candidate for further investigation into colorectal cancer outcome disparities.

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