• Hidetaka Kawamura, Tomotaka Ugai, Yasutoshi Takashima, Kazuo Okadome, Takashi Shimizu, Kosuke Mima, Naohiko Akimoto, Koichiro Haruki, Kota Arima, Melissa Zhao, Juha P Väyrynen, Kana Wu, 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, and Shuji Ogino.
• Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
• Ann. Surg. 2024 May 6.

ObjectiveTo test hypotheses that appendectomy history might lower long-term colorectal cancer risk and that the risk reduction might be strong for tumors enriched with Fusobacterium nucleatum, bacterial species implicated in colorectal carcinogenesis.BackgroundThe absence of the appendix, an immune system organ and a possible reservoir of certain pathogenic microbes, may affect the intestinal microbiome, thereby altering long-term colorectal cancer risk.MethodsUtilizing databases of prospective cohort studies, namely the Nurses' Health Study and the Health Professionals Follow-up Study, we examined the association of appendectomy history with colorectal cancer incidence overall and subclassified by the amount of tumor tissue Fusobacterium nucleatum​​ (Fusobacterium animalis). We used an inverse probability weighted multivariable-adjusted duplication-method Cox proportional hazards regression model.ResultsDuring the follow-up of 139,406 participants (2,894,060 person-years), we documented 2811 incident colorectal cancer cases, of which 1065 cases provided tissue F. nucleatum analysis data. The multivariable-adjusted hazard ratio of appendectomy for overall colorectal cancer incidence was 0.92 (95% CI, 0.84-1.01). Appendectomy was associated with lower F. nucleatum-positive cancer incidence (multivariable-adjusted hazard ratio, 0.53; 95% CI, 0.33-0.85; P=0.0079), but not F. nucleatum-negative cancer incidence (multivariable-adjusted hazard ratio, 0.98; 95% CI, 0.83-1.14), suggesting a differential association by F. nucleatum status (Pheterogeneity=0.015). This differential association appeared to persist in various participant/patient strata including tumor location and microsatellite instability status.ConclusionsAppendectomy likely lowers the future long-term incidence of F. nucleatum-positive (but not F. nucleatum-negative) colorectal cancer. Our findings do not support the existing hypothesis that appendectomy may increase colorectal cancer risk.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

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