Association of Polygenic Risk Score and Bacterial Toxins at Screening Colonoscopy with Colorectal Cancer Progression: A Multicenter Case-Control Study

Abstract

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and its incidence is correlated with infections, chronic inflammation, diet, and genetic factors. An emerging aspect is that microbial dysbiosis and chronic infections triggered by certain bacteria can be risk factors for tumor progression. Recent data suggest that certain bacterial toxins implicated in DNA attack or in proliferation, replication, and death can be risk factors for insurgence and progression of CRC. In this study, we recruited more than 300 biopsy specimens from people undergoing colonoscopy, and we analyzed to determine whether a correlation exists between the presence of bacterial genes coding for toxins possibly involved in CRC onset and progression and the different stages of CRC. We also analyzed to determine whether CRC-predisposing genetic factors could contribute to bacterial toxins response. Our results showed that CIF toxin is associated with polyps or adenomas, whereas pks+ seems to be a predisposing factor for CRC. Toxins from Escherichia coli as a whole have a higher incidence rate in adenocarcinoma patients compared to controls, whereas Bacteroides fragilis toxin does not seem to be associated with pre-cancerous nor with cancerous lesions. These results have been obtained irrespectively of the presence of CRC-risk loci.

Effects of the Escherichia coli Bacterial Toxin Cytotoxic Necrotizing Factor 1 on Different Human and Animal Cells: A Systematic Review

“…Several modifications induced by CNF1 are, in fact, reminiscent of a procarcinogenic potential [111,112]. In recent years, studies have been carried out to corroborate this hypothesis [21,113], but the subject of study is still in its infancy.…”

Role of the Microbiota in Lung Cancer: Insights on Prevention and Treatment

“…Several bacterial pathogens can produce enzymatically active protein toxins that can directly attack and damage DNA or become involved in essential host cell signaling pathways that direct cell proliferation, apoptosis, and inflammation [ 68 ]. The E. coli colibactin and cytolethal distending toxin (CDT) are significant examples of bacterial toxins able to induce mutations and genome instability, whereas the Bacteroides fragilis toxin, the E. coli Cif and cytotoxic necrotizing factor 1 (CNF1), the Fusobacterium nucleatum FadA, and the Salmonella AvrA are prototypes of toxins that engage signaling pathways, ultimately leading to transformation [ 68 , 69 ]. Chronic inflammation can contribute to colorectal cancer via several mechanisms, including the induction of the epithelial–mesenchymal transition (EMT), a process involved in metastasis, invasion, and cancer progression.…”

The Role of Cyclomodulins and Some Microbial Metabolites in Bacterial Microecology and Macroorganism Carcinogenesis

“…Although, in in vitro experiments, CIF inhibited the proliferation of cancer cells and eventually led to apoptosis, where new epidemiological data confirm the role of CIF in carcinogenesis. In a recent multicenter case-control study, an association of the cif gene with precancerous lesions—intestinal polyps or adenomas—was found that can occur in the early stages of carcinogenesis, and this association has been assessed as a statistically significant risk factor [ 37 ].…”