Abstract B002: History of appendectomy and colorectal cancer oncidence, overall and by intratumoral fusobacterium nucleatum status

Abstract Background: Evidence suggests that Fusobacterium nucleatum (F. nucleatum) plays a role in colorectal carcinogenesis by suppressing the host immune response to tumors. The appendix is an organ that may influence the intestinal microbiome. We hypothesized that appendectomy history might be associated with altered colorectal cancer incidence and that the association might differ by the amount of F. nucleatum in tumor tissue. Methods: Utilizing the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined the association of appendectomy history with the incidence of colorectal cancer overall and tumor subtypes classified by the amount of intratumoral F. nucleatum. We used an inverse probability weighted multivariable Cox proportional hazards regression model to control for potential confounders and selection bias due to tissue availability and potential confounders. Results: During follow-up of 139,424 participants (2,894,345 person-years), we documented 2,819 colorectal cancer cases, including 1,069 cases with available intratumoral F. nucleatum data. While appendectomy history was not statistically significantly associated with the incidence of colorectal cancer [multivariable-adjusted hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.84 to 1.01, P=0.068], the association of appendectomy history with colorectal cancer incidence differed by intratumoral F. nucleatum status (Pheterogeneity=0.013). Appendectomy history was associated with reduced incidence of F. nucleatum-positive tumors (multivariable-adjusted HR, 0.52; 95% CI, 0.33 to 0.84, P=0.0067), but not F. nucleatum-negative tumors (multivariable-adjusted HR, 0.98; 95% CI, 0.84 to 1.14, P=0.79). Conclusions: We found that appendectomy history was associated with reduced incidence of F. nucleatum-positive (but not F. nucleatum-negative) colorectal cancer. Our findings suggest that an appendectomy may change the intestinal microbiota, thereby altering potential pathogenic effect of F. nucleatum. Citation Format: Tomotaka Ugai, Hidetaka Kawamura, Yasutoshi Takashima, Kazuo Okadome, Takashi Shimizu, Kosuke Mima, Seyed Mostafa Mousavi Kahaki, Melissa Zhao, Juha P. Väyrynen, Xuehong Zhang, Kimmie Ng, Jonathan A. Nowak, Jeffrey A. Meyerhardt, Edward L. Giovannucci, Marios Giannakis, Andrew T. Chan, Curtis Huttenhower, Wendy S. Garrett, Mingyang Song, Shuji Ogino. History of appendectomy and colorectal cancer oncidence, overall and by intratumoral fusobacterium nucleatum status [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr B002.