Increased colon cancer risk after severe Salmonella infection

Abstract

BackgroundColon cancer constitutes one of the most frequent malignancies. Previous studies showed that Salmonella manipulates host cell signaling pathways and that Salmonella Typhimurium infection facilitates colon cancer development in genetically predisposed mice. This epidemiological study examined whether severe Salmonella infection, usually acquired from contaminated food, is associated with increased colon cancer risk in humans.Methods and findingsWe performed a nationwide registry-based study to assess colon cancer risk after diagnosed Salmonella infection. National infectious disease surveillance records (1999–2015) for Dutch residents aged ≥20 years when diagnosed with salmonellosis (n = 14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected patients were laboratory-confirmed under medical consultation after 1–2 weeks of illness. These datasets also contained information on Salmonella serovar and type of infection. Colon cancer risk (overall and per colon subsite) among patients with a diagnosed Salmonella infection was compared with expected colon cancer risk in the general population. Data from the nationwide registry of histo- and cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing potential effects of age, gender, latency, socioeconomic status, genetic predisposition, inflammatory bowel disease (IBD), and tumor features. We found that compared to the general population, colon cancer risk was significantly increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09–2.10) among patients with Salmonella infection diagnosed <60 years of age. Such increased risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38–3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73–4.76). Salmonellosis occurred more frequently among colon cancer patients with pre-infectious IBD, a known risk factor for colon cancer. Colon tumors of patients with a history of Salmonella infection were mostly of low grade.ConclusionsPatients diagnosed with severe salmonellosis have an increased risk of developing cancer in the ascending/transverse parts of the colon. This risk concerns particularly S. Enteritidis infection, suggesting a contribution of this major foodborne pathogen to colon cancer development.

Infection with genotoxin‐producingSalmonella entericasynergises with loss of the tumour suppressorAPCin promoting genomic instability via the PI3K pathway in colonic epithelial cells

“…Collectively, these data highlight the carcinogenic potential of the TT and provide a molecular mechanism to support the epidemiological observations linking chronic Salmonella infection with increased cancer risk not only in the hepatobiliary tract but also in the colon (Dutta et al, 2000;Mughini-Gras et al, 2018).…”

Bacterial infections and cancer

“…Typhi and S . Enteritidis, are linked to gallbladder carcinoma and colon cancer, respectively . These bacteria introduce a series of effector proteins in the host cell to take over host cell biology and—depending on host pathway affected—can contribute to cancer formation.…”

“…CdtA and CdtC ensure the uptake and cellular delivery of CdtB, which harbours the catalytic activity of CDT and causes double-strand DNA breaks (DSBs) in host cells. After host cell binding and internalization by Salmonella Typhi Bacterium Gallbladder carcinoma [13] Salmonella Enteritidis Bacterium Colon carcinoma in the ascending and transverse parts of the colon [14] Chlamydia trachomatis Bacterium Carcinoma of the cervix and ovaries [104,105] particularly sensitive to these toxins. As a result, this toxin can locally eliminate immune cells, providing an obvious advantage for the bacteria.…”

“…Typhi) infections and gallbladder carcinoma , and Salmonella Enteritidis ( S . Enteritidis) infections and colon carcinoma . Moreover, studies in germ‐free and antibiotic‐treated animals have indicated cancer‐promoting effects of microbiota in various experimental systems, varying from gastric , colon and liver cancers.…”

“…Although these microorganisms usually do not leave a genetically recognizable trait or piggyback on mammalian genes, such as illustrated by viral infections, strong epidemiological links exist between various microbiological infections and cancers (Table 1). Examples include connections between Schistosoma haematobium infections and bladder cancer [11], Helicobacter pylori (H. pylori) infections and gastric cancer [12], chronic Salmonella Typhi (S. Typhi) infections and gallbladder carcinoma [13], and Salmonella Enteritidis (S. Enteritidis) infections and colon carcinoma [14]. Moreover, studies in germ-free and antibiotic-treated animals have indicated cancerpromoting effects of microbiota in various experimental systems, varying from gastric [15,16], colon [17,18] and liver [19] cancers.…”