Abstract 3586: Fusobacterium nucleatum presence and colorectal cancer-specific mortality in a racially and ethnically diverse patient population
Authors: Nicole C. Loroña, Scott D. LaBrie, Claire E. Thomas, Hang Yin, Jeroen Huyghe, Conghui Qu, Sushma Thomas, Sosun Nayemi, Hamza Ammar, Orsalem Kahsai, Li Hsu, Diana Redwood, Li Li, Christopher I. Li, Ulrike Peters, Timothy K. Thomas, Amanda I. Phipps, Jane C. Figueiredo, Meredith Hullar
Journal: Cancer Research (2025)

Abstract Purpose: There are persistent racial and ethnic disparities in colorectal cancer (CRC) mortality. We examine the association between prevalence of Fusobacterium nucleatum (Fn) in tumor tissue and CRC-specific mortality in a diverse population. Methods: The present study includes 569 African American, Alaska Native, Latinx, and non-Hispanic White adults with stage I-III CRC who were part of the Translational Research Program in Colorectal Cancer Disparities (TRPCD). 188 patients with CRC who died of CRC were matched to 381 patients with CRC who did not die of CRC. Genomic DNA was extracted from colorectal tumor tissue samples. Droplet digital polymerase chain reaction (ddPCR) was used to analyze 1) the nusG gene from Fn (Fn(nusG)), and 2) the SLCO2A1 gene as a housekeeping (HK) gene reference from the human genome. Fn(nusG) positive droplet counts were normalized by HK gene positive droplet counts for each duplicated assay, and then averaged. Fn(nusG) prevalence was analyzed as a dichotomous variable in primary analyses (not present, present) and as a categorical variable (not present, low prevalence, high prevalence). The median normalized average Fn(nusG) count among those with Fn(nusG) present was the cut-point between low and high prevalence. We fit logistic regression models for the association between Fn(nusG) presence and CRC-specific mortality, adjusted for matching factors (age at diagnosis, year of diagnosis, sex, stage, tumor site, race and ethnicity). Effect modification by age, sex, stage, tumor site, and racial and ethnic group was assessed using a likelihood ratio test. Results: Fn(nusG) was present in tumors for 24% of patients with CRC who died of CRC (N=46) and 16% of patients with who did not die of CRC (N=61). Presence was lower in patients who were Alaska Native (14%), with stage I CRC (12%), and with rectal cancer (16%), and higher in those diagnosed in 2011-2017 (22%). Presence of Fn(nusG) was associated with a higher odds of CRC-specific mortality (OR: 1.76; 95% CI: 1.12-2.74), relative to no presence of Fn(nusG), after adjustment for matching factors. Estimates for the association between low prevalence (OR: 1.77; 95% CI: 0.97-3.21) and high prevalence (OR: 1.74; 95% CI: 0.95-3.14), relative to no presence of Fn(nusG), and CRC-specific mortality were similar. Further analysis is underway. Conclusions: These findings provide evidence of an association between presence of fusobacterium in CRC tumor tissue and CRC-specific mortality in a diverse population. As the association did not differ by low or high prevalence of fusobacterium, any amount of fusobacterium in CRC tumor tissue may confer poorer prognosis. Fusobacterium may contribute less to CRC-specific mortality in Alaska Native patients with CRC. Identifying microbiota associated with CRC mortality can inform targeted interventions to address racial and ethnic disparities in this disease. Citation Format: Nicole C. Loroña, Scott D. LaBrie, Claire E. Thomas, Hang Yin, Jeroen Huyghe, Conghui Qu, Sushma Thomas, Sosun Nayemi, Hamza Ammar, Orsalem Kahsai, Li Hsu, Diana Redwood, Li Li, Christopher I. Li, Ulrike Peters, Timothy K. Thomas, Amanda I. Phipps, Jane C. Figueiredo, Meredith Hullar. Fusobacterium nucleatum presence and colorectal cancer-specific mortality in a racially and ethnically diverse patient population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3586.