The Role of Hemophilus influenzae Infection and Its Relationship With Colorectal Cancer

Marla C. Fortoul, Enoch Kim, Amalia D. Ardeljan, Lexi Frankel, Kazuaki Takabe, Omar M. Rashid


Background: Hemophilus influenzae is a gram-negative coccobacillus. Non-typeable H. influenzae infection is a significant cause of disease that activates the inflammatory pathway involving the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome. A gain-of-function mutation in NLRP3 results in cryopyrin-associated periodic syndromes characterized by inflammatory conditions in the lungs, skin, joints, and eyes but not in the gut. This leads to homeostasis of the gut microbiota, which reduces inflammation and may have protective effect against colorectal cancer (CRC). This study aimed to evaluate the correlation between H. influenzae infection and the incidence of CRC.

Methods: A retrospective study was conducted from 2010 to 2019 using a HIPAA-compliant national database. ICD-10, ICD-9, CPT, and National Drug Codes were used to identify patients with or without a history of H. influenzae infection. Standard statistical methods were used to analyze the outcomes.

Results: The query was analyzed and matched, resulting in 13,610 patients in both groups. The incidence of CRC was 167 and 446 in the H. influenzae and control groups, respectively. The difference was statistically significant with P < 2.2 0-16 and an odds ratio of 0.41 (95% confidence interval: 0.36 - 0.47). Additionally, the groups were further evaluated and matched by treatment, which resulted in a statistically significant decrease in CRC incidence in the H. influenzae group.

Conclusion: This study showed a statistically significant correlation between H. influenzae and the reduced incidence of CRC. This reduction in CRC in patients with a history of H. influenzae infection suggests a potential link to the NLRP3 inflammasome, which should be further studied.

World J Oncol. 2023;14(3):188-194


Colorectal cancer; H. influenzae; Non-typeable H. influenzae; NLRP3 inflammasome; Microbiome; Gut-lung axis

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