Yannick Eisele1, Patrick M Mallea2, Biljana Gigic3, W Zac Stephens4, Christy A Warby2, Kate Buhrke4, Tengda Lin2, Juergen Boehm2, Petra Schrotz-King5, Sheetal Hardikar2, Lyen C Huang6, T Bartley Pickron6, Courtney L Scaife6, Richard Viskochil2, Torsten Koelsch3, Anita R Peoples2, Maria A Pletneva7, Mary Bronner7, Martin Schneider3, Alexis B Ulrich3, Eric A Swanson4, Adetunji T Toriola8, David Shibata9, Christopher I Li10, Erin M Siegel11, Jane Figueiredo12, Klaus-Peter Janssen13, Hans Hauner14, June Round4, Cornelia M Ulrich2, Andreana N Holowatyj15, Jennifer Ose16. 1. Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT; Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA. 2. Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT. 3. Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany. 4. Department of Pathology, University of Utah, Salt Lake City, UT. 5. Division of Preventive Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany. 6. Division of General Surgery, Department of Surgery, School of Medicine, University of Utah, Salt Lake City, UT. 7. Huntsman Cancer Institute, Salt Lake City, UT; Department of Pathology, University of Utah, Salt Lake City, UT. 8. Washington University in St. Louis, St. Louis, MO. 9. Department of Surgery, University of Tennessee Health Science Center, Memphis, TN. 10. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA. 11. Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL. 12. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA. 13. Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany. 14. Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Else Kröner-Fresenius-Centre for Nutritional Medicine, School of Life Sciences, Technical University of Munich, Munich, Germany. 15. Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Vanderbilt-Ingram Cancer Center, Nashville, TN. Electronic address: andreana.holowatyj@vumc.org. 16. Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT. Electronic address: jennifer.ose@hci.utah.edu.
Abstract
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-naïve 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-naïve CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.
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-naïve 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-naïve CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.
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