4.6 Article

Repetitive non-typhoidal Salmonella exposure is an environmental risk factor for colon cancer and tumor growth

Journal

CELL REPORTS MEDICINE
Volume 3, Issue 12, Pages -

Publisher

CELL PRESS
DOI: 10.1016/j.xcrm.2022.100852

Keywords

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Funding

  1. KWF grant
  2. ERC Advanced grant ERCOPE
  3. Netherlands Organisation for Health Research and Development (ZonMw) [522004001]
  4. UIC Cancer Center Fund
  5. LUMC MSCA-IF Seal of Excellence program

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Salmonella infection disrupts cellular integrity and may induce oncogenic transformation. Systemic S. Typhi infection is associated with gallbladder cancer, while severe non-typhoidal Salmonella infection is associated with colon cancer. A serological study found a significant positive correlation between exposure to non-typhoidal Salmonella and colon cancer risk.
During infection, Salmonella hijacks essential host signaling pathways. These molecular manipulations disrupt cellular integrity and may induce oncogenic transformation. Systemic S. Typhi infections are linked to gallbladder cancer, whereas severe non-typhoidal Salmonella (NTS) infections are associated with colon cancer (CC). These diagnosed infections, however, represent only a small fraction of all NTS infections as many infections are mild and go unnoticed. To assess the overall impact of NTS infections, we performed a retrospective serological study on NTS exposure in patients with CC. The magnitude of exposure to NTS, as measured by serum antibody titer, is significantly positively associated with CC. Repetitively infecting mice with low NTS exposure showed similar accelerated tumor growth to that observed after high NTS exposure. At the cellular level, NTS preferably infects (pre-)transformed cells, and each infection round exponentially increases the rate of transformed cells. Thus, repetitive exposure to NTS associates with CC risk and accelerates tumor growth.

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