Appendectomy and Long-term Colorectal Cancer Incidence, Overall and by Tumor Fusobacterium nucleatum Status.

Objective: To 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.
Background: The 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.
Methods: Utilizing 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.
Results: During 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.
Conclusions: Appendectomy 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.
Competing Interests: A.T.C. previously served as a consultant for Bayer Healthcare and Pfizer Inc. M.G. was on an advisory board for AstraZeneca and receives research funding from Bristol-Myers Squibb. J.A.M. has served as an advisor/consultant to Merck Pharmaceuticals and COTA Healthcare. K.W. is currently a stakeholder and employee of Vertex Pharmaceuticals. This study was not funded by any of these commercial entities. The remaining authors report no conflicts of interest.
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