Salmonella Typhi carriage and gallbladder cancer

Chronic carriage of Salmonella enterica serovar Typhi in the gallbladder, often on stones, is the infectious risk factor for gallbladder cancer in the Indian subcontinent and historically in Chile. A Chilean case-control study (39 cases, 40 gallstone controls, 39 population controls) found higher Vi antibody titres in cases (odds ratio 4.0, 95% CI 0.9 to 18.3) although the organism was not recovered from bile, stones, tissue or stool; the accompanying meta-analysis 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 (2.7 to 9.3) for bile or stool culture (Koshiol 2016). Mechanistically, Salmonella enterica induced malignant transformation in predisposed mice, murine gallbladder organoids and fibroblasts carrying TP53 mutation and c-MYC amplification; effector proteins secreted during infection activated MAPK and AKT signalling, which was needed both to start and to sustain transformation, consistent with observations in Indian patients (Scanu 2015). The finding gives a biological reason for the very early age of onset in India and for typhoid control and cholecystectomy of carriers as prevention.