Normalized counts of F. nucleatum were consistently higher in tumor tissue than in patient-matched normal tissue across all risk factors, while alpha diversity was lower, with female sex associated with high presence and enrichment of F. nucleatum in tumor tissue and younger age associated with lower alpha diversity.
Key Findings
Results
F. nucleatum normalized counts were consistently higher in tumor tissue than in patient-matched normal tissue across all risk factors.
Comparison was made using tumor and paired normal colorectal tissue samples from participants in the population-based Seattle Colon Cancer Family Registry.
F. nucleatum was measured via droplet digital PCR in n=898 participants.
This pattern of higher F. nucleatum in tumor versus normal tissue held across all demographic, health behavior, and neighborhood socioeconomic status subgroups examined.
Results
Alpha diversity (Shannon index) was consistently lower in tumor tissue than in patient-matched normal tissue across all risk factors.
Alpha diversity was measured via 16S rRNA gene sequencing in n=611 participants.
Shannon index was used as the measure of alpha diversity.
This pattern of lower diversity in tumor versus normal tissue held across all subgroups examined.
Results
Female sex was associated with high presence of F. nucleatum in tumor tissue.
Odds ratio for high presence of F. nucleatum in tumor tissue among females: OR 1.61 (95% CI 1.02, 2.54).
Female sex was also associated with enrichment of F. nucleatum in tumor tissue: OR 1.58 (95% CI 1.10, 2.27).
Both high presence and enrichment were statistically significant associations for female sex.
Results
The youngest age group (under 40 years) had lower alpha diversity in tumor tissue compared to those aged 40-49 years.
OR for highest vs. lowest tertile of alpha diversity in tumor tissue for the under-40 age group relative to the 40-49 age group: OR 0.33 (95% CI 0.13, 0.83).
This indicates that the youngest patients were less likely to be in the highest tertile of tumor tissue alpha diversity.
Age groups were compared relative to those aged 40-49 years as the reference group.
Results
Diet and other epidemiologic factors were not related to F. nucleatum presence or tumor tissue alpha diversity.
Factors examined included demographics, health behaviors, diet, and neighborhood socioeconomic status (nSES).
No significant associations were found between diet and F. nucleatum presence in tumor tissue.
No significant associations were found between diet and tumor tissue alpha diversity.
Only female sex and youngest age group showed statistically significant associations with F. nucleatum presence/enrichment and alpha diversity, respectively.
Methods
The study used a population-based sample from the Seattle Colon Cancer Family Registry to examine intratumoral microbiota.
Sample size for F. nucleatum analysis: n=898; sample size for alpha diversity analysis: n=611.
F. nucleatum was measured via droplet digital PCR and alpha diversity via 16S rRNA gene sequencing.
Tumor and paired normal colorectal tissue samples were used, allowing within-patient comparisons.
Epidemiologic factors examined included demographics, health behaviors, diet, and neighborhood socioeconomic status.
Hill C, Malen R, Reedy A, Kahsai O, Curtis K, Ma N, et al.. (2026). Associations of epidemiologic risk factors with Fusobacterium nucleatum and bacterial alpha diversity in the colorectal tumor-associated microbiota.. Cancer causes & control : CCC. https://doi.org/10.1007/s10552-026-02133-4