Incidence of Colorectal Cancer After Intestinal Infection Due to Clostridioides difficile.

Abstract

Background: Clostridioides difficile (C. difficile or C. diff) is a toxin-producing bacteria that is notorious for causing life-threatening diarrhea. Recent literature has investigated various effects of Clostridioides difficile infection (CDI) in cancer patients, but research into the impact of CDI on the development of cancer and its effects on the microbiome is limited. CDI predominately affects the colon, which urges consideration into the sequalae of infection. This study investigated the correlation between CDI and the incidence of colorectal carcinoma (CRC).

Methods: A retrospective study (2010 - 2020) was conducted using a Health Insurance Portability and Accountability Act (HIPAA) compliant national database. The International Classification of Disease ninth and 10th Codes (ICD-9, ICD-10), Current Procedural Terminology (CPT), and National Drug Codes were used to identify CRC diagnosis, CDI, and matching or control parameters. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), region of residence, and CDI treatment. An additional, but separate, query was executed to include obese patients with and without CDI, who were similarly matched and assessed for CRC. Statistical analyses were implemented to assess significance and estimate odds ratios (ORs).

Results: CDI was associated with a decreased incidence of CRC (OR = 0.59, 95% confidence interval (CI): 0.55 - 0.63), and the difference was statistically significant (P < 2.2 × 10^-16). CDI treatment, including appropriate antibiotics and fecal microbiota transplant (FMT), was controlled for in both infected and noninfected populations. Patients with a prior CDI who received relevant treatment were compared to patients with no history of CDI and received analogous treatment. Both populations subsequently developed CRC. Results remained statistically significant (P < 2.2 × 10^-16) with a relative risk (RR) of 0.57 (95% CI: 0.54 - 0.60). Obesity was explored as a controlled variable in relation to CRC development in patients with and without prior CDI. Obese patients without a history of CDI were found to have a decreased risk of developing CRC. Results were statistically significant (P < 4.3 × 10^-13) with an OR of 0.70 (95% CI: 0.63 - 0.77).

Conclusions: This study shows a statistically significant correlation between CDI and decreased incidence of CRC. Additionally, there is a statistically significant correlation between obese patients with CDI and an increased incidence of CRC. Further research is needed to explore the mechanism of this striking relationship and the implications of CDIs on the microbiome.