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

Toxins (Basel). 2021 Aug 16;13(8):569. doi: 10.3390/toxins13080569.

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.

Keywords: bacterial protein toxins; colorectal cancer; gut microbiota screening; host–pathogens interaction; mucosa adherent bacteria; polygenic risk score.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bacterial Toxins / genetics*
  • Bacterial Toxins / toxicity*
  • Case-Control Studies
  • Colonoscopy / statistics & numerical data
  • Colorectal Neoplasms / chemically induced*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / microbiology*
  • Disease Progression
  • Enterotoxigenic Escherichia coli
  • Enterotoxins
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Healthy Volunteers
  • Host-Pathogen Interactions / drug effects
  • Humans
  • Male
  • Middle Aged
  • Multifactorial Inheritance / genetics*
  • Risk Factors
  • Young Adult

Substances

  • Bacterial Toxins
  • Enterotoxins