"Driver or passenger" : an integrated epidemiological and experimental perspective on the association between nontyphoidal salmonella infection and colon cancer

A growing body of scientific literature documents a putative role of commensal and pathogenic bacteria in the initiation and progression of cancers. One such bacterium is nontyphoidal Salmonella (NTS), which has been associated with colon cancer in a few studies. Yet, a lot is still unknown about the magnitude and underlying mechanisms, including the necessary conditions or ‘prerequisites’, of the potential colon carcinogenesis promoting effects of Salmonella. In this thesis, we performed several complementary analyses based on both experimental and epidemiological study designs. Significant excess risk of NTS infection was observed among several occupational groups including those involving contact with live animals or animal manure and animal-derived food sale. The risk of colon cancer was not elevated in these groups. Also, no clear association between NTS and colon cancer was found in a Danish cohort. Two-fold infection of mouse embryonic fibroblasts (MEFs) with a low dose of NTS was more successful than a single high-dose infection (i.e. more and larger colonies). Substantial variation between NTS isolates was found in their capacity to infect MEFs and to induce cellular transformation, with a tendency towards higher transformation efficiency in isolates originating from people who were diagnosed with colon cancer later in life.Dutch Cancer Society (KWF); ZonMWLUMC / Geneeskund