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People who carry typhoid bacteria in their gallbladder for years have roughly four to five times the risk of gallbladder cancer. Laboratory work shows the bacterium can push already-damaged gallbladder cells towards 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.
In plain words · TP53 is the 'guardian of the genome', broken in half of all cancers. Fixing it directly has so far defeated every attempt, so drugs exploit what its loss makes cancers depend on.
Showing the target this term concerns: TP53.
Typhoid carriage is one of the few modifiable risk factors for gallbladder cancer. In the UK it is rare, but it matters for people who grew up where typhoid is endemic and for the question of whether chronic carriers should be offered cholecystectomy.
A mechanism for the oldest epidemiological clue in gallbladder cancer, and a reason the disease appears so early in India. It frames typhoid control and cholecystectomy in chronic carriers as cancer prevention, and MAPK and AKT as pathways worth watching in infection-associated tumours.
Shares Salmonella enterica serovar Typhi and gallbladder cancer: a case-control study and meta-analysis, Gallbladder cancer.
Shares Salmonella enterica serovar Typhi and gallbladder cancer: a case-control study and meta-analysis, Gallbladder cancer.
Shares PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK), TP53.
Shares PI3K / AKT / mTOR, RAS / RAF / MEK / ERK (MAPK), TP53.
Shares RAS / RAF / MEK / ERK (MAPK), TP53.