Fusobacterium Nucleatum Enrichment in Colorectal Cancer and its Relationship with Tumor Attributes

Thesis (Master's)--University of Washington, 2021Background: Aspects of the human gut microbiome have recently been linked to the etiology of colorectal cancer (CRC). Specifically, the commensal microbe Fusobacterium nucleatum (F. nucleatum) has been implicated in the development and progression of CRC, and has been found to be enriched in colorectal tumor tissue. Reflecting the fact that CRC is a heterogenous disease, F. nucleatum enrichment in CRC has been suggested to associate with various tumor molecular characteristics. Methods: In this study, we used matched tumor and normal adjacent tissue collected from 403 participants in the Puget Sound Colorectal Cancer Cohort study to quantify the amount of F. nucleatum DNA in each respective tissue sample. Based on these generated data, we determined trends in tissue enrichment among tumors exhibiting different molecular and phenotypic characteristics of etiologic interest. Logistic regression was used to determine the odds of tumor tissue enrichment among tumors exhibiting different clinicopathologic and molecular characteristics, adjusting for age, sex, and BMI. Results: F. nucleatum enrichment in tumor (relative to matched normal tissue) was found in 25% of samples analyzed. Samples from right sided tumors (OR: 2.67; 95% CI: 1.64, 4.74), MSI-high samples (OR: 2.81; 95% CI: 1.99, 3.93), and those with a mutation in the BRAF v600E gene (OR: 1.75; 95% CI: 1.09, 2.67) had significantly higher odds of F. nucleatum enrichment. Conclusions: While CRC is a well-described disease, the relationship between its development and features of the gut microbiome (including F. nucleatum) are still becoming understood. The results of this study provide evidence linking F. nucleatum enrichment in tumor tissue to various molecular and phenotypic tumor attributes, and highlight several gaps in our understanding of the relationship between the development of CRC and the gut microbiome