Site‐ and age‐dependent associations between Fusobacterium nucleatum and colorectal cancer mortality

BACKGROUND: Fusobacterium nucleatum (Fn) is a bacterium typically found in the human oral cavity that has been implicated in the development and progression of colorectal cancer (CRC). OBJECTIVE: This study examines the association between prevalence of Fn in tumor tissue and CRC-specific mortality in a heterogeneous United States population. METHODS: The present study includes 233 participants with stage I-III CRC who died of CRC, matched to 458 participants with CRC who did not die from their disease, within the Translational Research Program in Cancer Differences across Populations. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor tissue samples. Droplet digital polymerase chain reaction was used to assess the prevalence of Fn. The authors fit logistic regression models for the association between Fn positivity and CRC-specific mortality, adjusting for age, year of diagnosis, sex, stage, tumor site, population group, and tumor macrodissection status. RESULTS: Presence of Fn in CRC tumor tissue was associated with 79% greater odds (95% CI, 1.20-2.67) of CRC-specific mortality. This association was more pronounced in participants with rectal (odds ratio OR, 7.73; 95% CI, 2.13-34.79) than proximal colon (OR, 1.17; 95% CI, 0.65-2.08) or distal colon tumors (OR, 1.51; 95% CI, 0.74-3.04, p value for interaction = .023), and more pronounced with respect to early-onset (age <50 years; OR, 10.30; 95% CI, 2.09-70.53) than later-onset CRC (age ≥50 years; OR, 1.51; 95% CI, 0.98-2.33, p value for interaction = .010). CONCLUSIONS: These findings support an association between presence of Fn in CRC tumor tissue and CRC-specific mortality, particularly for rectal tumors and early-onset CRC, in a heterogeneous population.