Controlling bacterial infections responsible for typhoid fever could reduce the risk of gallbladder cancer in India and Pakistan, a team of scientists including an Indian researcher said.
The findings establish the causal link between bacterial infection and gallbladder cancer, explaining why this type of cancer is rare in the West but common in India and Pakistan, where typhoid fever is endemic.
"If Salmonella Typhi (typhoid causing bacteria) infections are cured immediately, we would expect a major reduction in the incidence of a tumour that represents the third most common gastrointestinal tumour in India and Pakistan," said Jacques Neefjes from the Netherlands Cancer Institute and the researcher.
Neefjes, along with colleague Tiziana Scanu and Gopal Nath of the Banaras Hindu University set out to gain insight into how to combat this tumour by identifying causal factors underlying its unique global distribution.
The researchers quickly zeroed in on S Typhi because this typhoid-causing bacterium is endemic in India and has been associated with gallbladder cancer in epidemiological studies.
Proteins that Salmonella injects into host cells activate cancer-related signalling pathways called AKT and MAPK which support not only bacterial infection and survival but also the growth and proliferation of cancer cells.
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To explore further, the team compared tumour samples from Indian and Dutch patients with gallbladder cancer.
While both groups showed signs of AKT and MAPK activation and an inactive mutant TP53 cancer gene, only Indian patients showed strong evidence of S. Typhi infection and over-activating mutations in a specific cancer gene.
To mimic the features of the tumour samples from India, the researchers transplanted Salmonella-infected cells with mutations affecting TP53 and the specific cancer gene into mice.
These mice later developed tumours, demonstrating that Salmonella causes cancer in genetically at-risk hosts as a result of the collateral damage induced by its normal infection cycle.
Gallbladder cancer is hard to diagnose in its early stages because there are no signs or symptoms of it and by the time it is detected, it is often too late to save patients' lives.
In future studies, the researchers will investigate whether Salmonella contributes to tumours in other tissues and identify other cancer-causing bacteria.
"If typhoid fever is controlled, gallbladder carcinoma in India and Pakistan could be prevented and become as rare as in the Western world," Neefjes said.
The paper was published in the journal Cell Host & Microbe.