During infection, Salmonella hijacks essential host signaling pathways. These molecular manipulations disrupt cellular integrity and may induce oncogenic transformation. Systemic S. Typhi... Show moreDuring 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. Show less
Duijster, J.W.; Franz, E.; Neefjes, J.; Mughini-Gras, L. 2021
The oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and... Show moreThe oncogenic potential of viral infections is well established and documented for many years already. However, the contribution of (commensal) bacteria and parasites to the development and progression of cancers has only recently gained momentum, resulting in a rapid growth of publications on the topic. Indeed, various bacteria and parasites have been suggested to play a role in the development of gastrointestinal cancer in particular. Therefore, an overview of the current epidemiological knowledge on the association between infections with bacteria and parasites and cancers of the gastrointestinal tract is needed. In this review, we summarized the methodological characteristics and main results of epidemiological studies investigating the association of 10 different bacteria (Bacteroides fragilis, Campylobacter spp., Clostridium spp., Enterococcus faecalis, Escherichia coli, Fusobacterium nucleatum, Porphyromonas gingivalis, non-typhoidal Salmonella, Salmonella Typhi, and Streptococcus spp.) and three parasites (Cryptosporidium spp., Schistosoma spp., and Strongyloides stercoralis) with gastrointestinal cancer. While the large body of studies based on microbiome sequencing provides valuable insights into the relative abundance of different bacterial taxa in cancer patients as compared to individuals with pre-malignant conditions or healthy controls, more research is needed to fulfill Koch's postulates, possibly making use of follow-up data, to assess the complex role of bacterial and parasitic infections in cancer epidemiology. Studies incorporating follow-up time between detection of the bacterium or parasite and cancer diagnosis remain valuable as these allow for estimation of cause-effect relationships. Show less
Duijster, J.W.; Hansen, J.V.; Franz, E.; Neefjes, J.J.C.; Frisch, M.; Mughini-Gras, L.; Ethelberg, S. 2021
Laboratory data increasingly suggest that Salmonella infection may contribute to colon cancer (CC) development. Here, we examined epidemiologically the potential risk of CC associated with... Show moreLaboratory data increasingly suggest that Salmonella infection may contribute to colon cancer (CC) development. Here, we examined epidemiologically the potential risk of CC associated with salmonellosis in the human population. We conducted a population-based cohort study using four health registries in Denmark. Person-level demographic data of all residents were linked to laboratory-confirmed non-typhoidal salmonellosis and to CC diagnoses in 1994-2016. Hazard ratios (HRs) for CC (overall/proximal/distal) associated with reported salmonellosis were estimated using Cox proportional hazard models. Potential effects of serovar, age, sex, inflammatory bowel disease and follow-up time post-infection were also assessed. We found no increased risk of CC >= 1 year post-infection (HR 0.99; 95% confidence interval (CI) 0.88-1.13). When stratifying by serovar, there was a significantly increased risk of proximal CC >= 1 year post-infection with serovars other than Enteritidis and Typhimurium (HR 1.40; 95% CI 1.03-1.90). CC risk was significantly increased in the first year post-infection (HR 2.08; 95% CI 1.48-2.93). The association between salmonellosis and CC in the first year post-infection can be explained by increased stool testing around the time of CC diagnosis. The association between proximal CC and non-Enteritidis/non-Typhimurium serovars is unclear and warrants further investigation. Overall, this study provides epidemiological evidence that notified Salmonella infections do not contribute significantly to CC risk in the studied population. Show less
Duijster, J.; Mughini-Gras, L.; Neefjes, J.; Franz, E. 2021
Objectives While colon cancer (CC) risk is associated with several lifestyle-related factors, including physical inactivity, smoking and diet, the contribution of occupation to CC morbidity remains... Show moreObjectives While colon cancer (CC) risk is associated with several lifestyle-related factors, including physical inactivity, smoking and diet, the contribution of occupation to CC morbidity remains largely unclear. Growing evidence indicates that gastrointestinal infections like salmonellosis could contribute to CC development. We performed a nationwide registry study to assess potential associations between occupation (history) and CC, including also those occupations with known increased exposure to gastrointestinal pathogens like Salmonella. Methods Person-level occupational data for all residents in The Netherlands were linked to CC diagnosis data. Differences in the incidence of (overall, proximal and distal) CC among occupational sectors and risk groups were tested for significance by calculating standardised incidence ratios (SIRs) with 95% CIs using the general population as reference group. Effects of gender, age, exposure duration and latency were also assessed. Results Significant differences in CC incidence were observed only for a few occupational sectors, including the manufacturing of rubber and plastics, machinery and leather, the printing sector and the information service sector (SIRs 1.06-1.88). No elevated risk of CC was observed among people with increased salmonellosis risk through occupational exposure to live animals, manure or among those working in the sale of animal-derived food products (SIRs 0.93-0.95, 0.81-0.95 and 0.93-1.09 for overall, proximal and distal CC, respectively). Conclusions The results of this study suggest that occupation in itself provides a relatively small contribution to CC incidence. This is consistent with previous studies where a similar degree of variation in risk estimates was observed. The lack of an association with the high-risk occupations for salmonellosis might be due to higher levels of physical activity, a known protective factor for CC and other diseases, of people working in the agricultural sector, which might outweigh the potential Salmonella-associated risk of CC. Show less
Duijster, J.W.; Franz, E.; Neefjes, J.J.C.; Mughini-Gras, L. 2019
