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

BACKGROUND: The microbiome is an important component of the tumor microenvironment implicated in colorectal cancer (CRC). However, its relationship with CRC-specific mortality remains unclear. METHODS: We included 581 participants with CRC (167 African American, 176 Alaska Native, 118 Hispanic, 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. 204 participants died of CRC and 377 did not die of CRC. Participants who died of CRC were matched to participants who did not die of CRC during follow-up by age, sex, tumor site, tumor stage, year of diagnosis, and population group. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between bacterial presence with CRC-specific mortality, adjusting for matching factors and tissue macrodissection status. RESULTS: Individuals who died from CRC 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 to other populations, however this different 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 CRC death. CONCLUSIONS: Fusobacteriota was significantly associated with CRC-specific mortality with noted differences across populations. IMPACT: This finding highlights the tumor microbiome as a candidate for further investigation into CRC outcome disparities.