Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis

Ivan Borozan, Syed H. Zaidi, Tabitha A. Harrison, Amanda I. Phipps, Jiayin Zheng, Stephen Lee, Quang M. Trinh, Robert S. Steinfelder, Jeremy Adams, Barbara L. Banbury, Sonja I. Berndt, Stefanie Brezina, Daniel D. Buchanan, Susan Bullman, Yin Cao, Alton B. Farris, Jane C. Figueiredo, Marios Giannakis, Lawrence E. Heisler, John L. HopperYi Lin, Xuemei Luo, Reiko Nishihara, Elaine R. Mardis, Nickolas Papadopoulos, Conghui Qu, Emma E.G. Reid, Stephen N. Thibodeau, Sophia Harlid, Caroline Y. Um, Li Hsu, Andrea Gsur, Peter T. Campbell, Steven Gallinger, Polly A. Newcomb, Shuji Ogino, Wei Sun, Thomas J. Hudson, Vincent Ferretti, Ulrike Peters

Research output: Contribution to journalArticlepeer-review


Background: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis. Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations. Results: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations. Conclusions: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.

Original languageEnglish (US)
Pages (from-to)210-220
Number of pages11
JournalCancer Epidemiology Biomarkers and Prevention
Issue number1
StatePublished - Jan 2022

ASJC Scopus subject areas

  • General Medicine


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