Salmonella enterica serovar Typhi and gallbladder cancer: a case-control study and meta-analysis
Pooling more than 1,000 cases, people with evidence of typhoid carriage had four to five times the odds of gallbladder cancer, and a new Chilean study pointed the same way even though the bacterium itself could not be cultured from the patients.
Overview
In Chile, where gallbladder cancer rates are high and typhoid fever was endemic until the 1990s, 39 gallbladder cancer cases, 40 gallstone controls and 39 population-based controls were tested for Salmonella Typhi Vi antibodies, with culture and quantitative PCR on available bile, gallstone, tissue and stool. Cases were more likely to have high Vi antibody titres than combined controls (odds ratio 4.0, 95% CI 0.9 to 18.3), although S. Typhi was not recovered from any sample.
A meta-analysis combining these results with previous studies of more than 1,000 cases gave a summary relative risk of 4.6 (95% CI 3.1 to 6.8) for anti-Vi antibody and 5.0 (95% CI 2.7 to 9.3) for bile or stool culture, with no heterogeneity. Despite differences in detection methods, most studies found a positive association.
- Summary relative risk 4.6 (95% CI 3.1 to 6.8) for anti-Vi antibody and 5.0 (2.7 to 9.3) for bile or stool culture across more than 1,000 cases.
- Chilean case-control odds ratio 4.0 (0.9 to 18.3) for high Vi titre; no organism cultured.
- Consistent direction across studies despite differing assays.
The quantitative case for typhoid as a gallbladder carcinogen, complementing the mechanism from Scanu 2015. Vaccination, sanitation and treating chronic carriers are the population-level levers this implies.
- Serology cannot date exposure; the Chilean odds ratio crosses one.
- Heterogeneous detection methods across the pooled studies.
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