Association Between Clostridioides difficile Test Positivity and Colorectal Cancer Incidence in a Multisite...

Area of Science:

• Gastroenterology
• Oncology
• Microbiology

Background:

• Sporadic colorectal cancer (CRC) is a major global health concern.
• Environmental factors, including gut dysbiosis and specific bacteria like Clostridioides difficile, are linked to CRC.
• Previous mouse studies suggest C. difficile toxin B promotes colon tumorigenesis, but human evidence is limited.

Purpose of the Study:

• To investigate the association between C. difficile infection and the risk of developing incident CRC in humans.
• To analyze a large, longitudinal Electronic Health Record (EHR) dataset to assess this link.
• To compare CRC risk in individuals with recurrent C. difficile positivity versus those with single or no positivity.

Main Methods:

• Analysis of a multicenter, longitudinal Electronic Health Record (EHR) dataset.
• Utilized unadjusted and multivariable Cox proportional hazard modeling.
• Compared cohorts based on C. difficile test positivity (recurrent, single, or never).

Main Results:

• Individuals with recurrent C. difficile positivity showed a significantly increased risk of incident CRC (adjusted Hazard Ratio [aHR] 2.05).
• Those with single C. difficile positivity did not have a significantly increased risk (aHR 0.70).
• Potential trends indicated a stronger effect of C. difficile positivity on CRC risk in females compared to males.

Conclusions:

• Recurrent C. difficile infections are associated with a significantly higher risk of developing colorectal cancer in humans.
• Findings translate animal model research to human data and warrant further investigation.
• Results may inform personalized fecal microbiota-based therapies to manage C. difficile and potentially prevent CRC.