Lexi R. Frankel

Developing clostridiodes difficile infections (CDI) actually may lessen the risk of prostate cancer, according to new research.

A team, led by Lexi R. Frankel, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, analyzed the effect of CDI on the risk of developing prostate cancer.

“More recently, studies have referenced the importance of focusing on targeting cytokine-containing immune pathways, immune intensification and immune modulation, the role of the microbiome in immunotherapy response, and identifying new biomarkers for [prostate cancer] development,” the authors wrote. “One potential pathogen that may play a surprising role in identifying such immune pathways and biomarkers for PC is Clostridium difficile.”

C. difficile causes the release of various proinflammatory cytokines, including interleukin (IL)-1β, IL-8, IL-16, and IL-17A, and several other regulatory and anti-inflammatory cytokines, including IL-10, IL-23, and IL-48, some of which increase in states of inflammation and cancer.

“Whether their presence stimulates carcinogenesis or if cancer stimulates tumoricidal cytokine recruitment has been debated profusely,” the authors wrote. “If the latter is true, then the cytokines released by C. difficile infection may prove useful in reducing PC development.”

In the retrospective cohort analysis, the investigators searched a national database to evaluqte the relationship between a prior history of CDI and subsequent development of prostate cancer between January 2010 and December 2019 of patients with and without a history of CDI.

Each group was matched by age range, Charlson Comorbidity Index (CCI), and antibiotic treatment exposure, including metronidazole, vancomycin, and fidaxomicin. The team also assessed demographic breakdowns of patient age at diagnosis of PC and region of residence.

The investigators sought primary outcomes of prostate cancer incidence.

The investigators identified 79,226 total patients and control participants matched by age and CCI.

The results show 2.56% (n = 1827) of the CDI group developed prostate cancer, compared to 7.79% (n = 5565) in the control group (p <2.2 × 10-16; Odds Ratio (OR), 0.390, 95% confidence interval (CI), 0.372-0.409).

The investigators then matched the patients by antibiotic exposure and found the prostate cancer incidence was 272 (1.62%) in the CDI group and 663 (3.95%) in the control group (p <2.2 × 10-16; OR, 0.467; 95% CI, 0.431-0.507).

The average time between treated C. difficile infection and PC diagnosis was 1,000 days and the average time between the control group with treatment exposure and PC diagnosis was 1,033 days.

“Results from this retrospective cohort study demonstrate that C. difficile infection is associated with a reduced incidence of [prostate cancer],” the authors wrote. “Future studies are recommended to investigate the potential effect of the immune system and cytokines related to C. difficile infection on [prostate cancer].”

References:

Frankel L R, Ardeljan A, Obaed N G, et al. (January 30, 2023) Clostridium difficile Infection Is Associated With Decreased Prostate Cancer Risk: A Retrospective Cohort Study. Cureus 15(1): e34398. doi:10.7759/cureus.34398