Salmonella entericaserovar Typhi and gallbladder cancer: a case–control study and meta‐analysis

Abstract

In Chile, where gallbladder cancer (GBC) rates are high and typhoid fever was endemic until the 1990s, we evaluated the association between Salmonella enterica serovar Typhi (S. Typhi) antibodies and GBC. We tested 39 GBC cases, 40 gallstone controls, and 39 population‐based controls for S. Typhi Vi antibodies and performed culture and quantitative polymerase chain reaction for the subset with bile, gallstone, tissue, and stool samples available. We calculated gender and education‐adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association with GBC. We also conducted a meta‐analysis of >1000 GBC cases by combining our results with previous studies. GBC cases were more likely to have high Vi antibody titer levels than combined controls (OR: 4.0, 95% CI: 0.9–18.3), although S. Typhi was not recovered from bile, gallstone, tissue, or stool samples. In our meta‐analysis, the summary relative risk was 4.6 (95% CI: 3.1–6.8, P heterogeneity=0.6) for anti‐Vi and 5.0 (95% CI: 2.7–9.3, P heterogeneity = 0.2) for bile or stool culture. Our results are consistent with the meta‐analysis. Despite differences in study methods (e.g., S. Typhi detection assay), most studies found a positive association between S. Typhi and GBC. However, the mechanism underlying this association requires further investigation

Global epidemiological trends and variations in the burden of gallbladder cancer

“…In Chile, GBC is mainly associated with chronic inflammation of the gallbladder wall due to the presence of gallstones . It also has been noted that the chronic presence of Salmonella typhi in the gallbladder can be a risk factor . This may be a long‐term consequence of the endemic typhoid fever that affected Chile during 1970s and 1980s .…”

“…It also has been noted that the chronic presence of Salmonella typhi in the gallbladder can be a risk factor . This may be a long‐term consequence of the endemic typhoid fever that affected Chile during 1970s and 1980s . On the other hand, in Chile it is very uncommon to see advanced GBC originating from a gallbladder polyp .…”

Pancreatic Cancer, Gut Microbiota, and Therapeutic Efficacy

“…The association of gut bacteria and tumor tissue has been previously reported, such as Helicobacter pylori and gastric cancer, Salmonella typhi and gallbladder cancer, and altered bacterial species and CRC [73][74][75]. These microorganisms within tumors may stimulate host immune responses and generate beneficial or disruptive impacts on anticancer therapy, as determined by pharmacological mechanisms, as well as the major response pathways [53].…”

Microbe-Driven Genotoxicity in Gastrointestinal Carcinogenesis

“…Despite the rising incidence in developed countries in North America and Europe [ 151 ], salmonellosis and more specifically typhoid fever, is endemic in developing countries such as India or nations in the western parts of South America. Interestingly, the incidence of gall bladder cancer in these regions is much higher (~20-fold) compared to the rest of the world [ 152 , 153 ]. Outbreaks in regions in which typhoid fever is typically not endemic have enabled a clear link to be made to corresponding increases in the rates of gall bladder cancer [ 154 , 155 ].…”