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Background Fusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood. Patients and Methods We examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-naive CRC patients enrolled in the international, prospective ColoCare Study. Electronic medical charts, including pathological reports, were reviewed to document clinicopathologic features. Quantitative real-time polymerase chain reaction (PCR) was used to amplify/detect Fn DNA in preoperative fecal samples. Multinomial logistic regression was used to analyze associations between Fn abundance and patient sex, age, tumor stage, grade, site, microsatellite instability, body mass index (BMI), alcohol consumption, and smoking history. Cox proportional hazards models were used to investigate associations of Fn abundance with overall survival in adjusted models. Results Compared to patients with undetectable or low Fn abundance, patients with high Fn abundance (n = 22) were 3-fold more likely to be diagnosed with rectal versus colon cancer (odds ratio [OR] = 3.01; 95% confidence interval [CI], 1.06-8.57; P = .04) after adjustment for patient sex, age, BMI, and study site. Patients with high Fn abundance also had a 5-fold increased risk of being diagnosed with rectal cancer versus right-sided colon cancer (OR = 5.32; 95% CI, 1.23-22.98; P = .03). There was no statistically significant association between Fn abundance and overall survival. Conclusion Our findings suggest that Fn abundance in fecal samples collected prior to surgery varies by tumor site among treatment-naive CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.

Background: Fusobacterium nucleatum (Fn), an oral commensal involved in a wide spectrum of infections, has recently been implicated in colorectal cancer (CRC) etiology. However, the role of Fn in treatment-naïve CRC patients remains unclear. Therefore, we assessed whether Fn abundance is associated with clinicopathologic characteristics among treatment-naïve CRC patients enrolled in the prospective ColoCare Study. Methods: Quantitative real-time PCR was used to amplify and detect Fn DNA in fecal samples collected prior to surgery from 105 patients. We utilized multivariable regression analysis to investigate associations between Fn abundance and sex, age at surgery, BMI, tumor stage, tumor grade, tumor site, infection with H. pylori, microsatellite instability, alcohol consumption, and smoking history by adjusting for sex, age at surgery, cohort, and BMI. Results: Compared to patients with undetectable or low abundance of Fn, patients with higher abundance of Fn were more likely to be diagnosed with rectal cancer than colon cancer (Odds Ratio [OR] = 3.01, 95% CI 1.06-8.57 P=0.04). Categorizing the colon into right-sided (proximal) and left-sided (distal) showed that patients with a high abundance of Fn were also more likely to be diagnosed with rectal cancer compared to right-sided colon cancer (OR=5.32, 95% CI 1.23-22.98 P=0.03), thus suggesting an increasing risk of cancer diagnosis along the bowel towards the rectum. Conclusion: Our study sheds light on the association of high abundance of Fn in fecal biospecimen with colorectal carcinogenesis, which may support future preventive or diagnostic measures. Citation Format: Yannick Eisele, Patrick M. Mallea, Biljana Gigic, W. Zac Stephens, Christy A. Warby, Kate Buhrke, Tengda Lin, Petra Schrotz-King, Sheetal Hardikar, Lyen C. Huang, T. Bartley Pickron, Courtney Scaife, Torsten Koelsch, Anita R. Peoples, Maria A. Pletneva, Mary Bronner, Martin Schneider, Alexis B. Ulrich, Eric A. Swanson, Adetunji T. Toriola, Hans Hauner, June Round, Cornelia M. Ulrich, Andreana N. Holowatyj, Jennifer Ose. Fusobacterium nucleatum and clinicopathologic features of colorectal carcinoma: Results from the ColoCare Study [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A01.