Role of bacteria in carcinogenesis, with special reference to carcinoma of the gallbladder

Abstract

Carcinoma of the gallbladder (CaGB) is the fifth commonest gastrointestinal tract cancer and is endemic in several countries. The interplay of genetic susceptibility, infections, and life style factors has been proposed to be responsible for carcinogenesis of gallbladder. Persistence of infection leading to chronic inflammation, and production of certain toxins and metabolites with carcinogenic potentials, by certain bacteria has been speculated to be involved in the transformation of the gallbladder epithelium. Therefore, any bacteria that have evolved to acquire both of the above carcinogenic mechanisms can cause cancer. Salmonella typhi has been found to be prominently associated with CaGB. Chronic typhoid carriage (persistence) and production of mediators of chronic inflammation and a genotoxic toxin (cytotoxic distending toxin, CdtB) are also known for this bacterium. Furthermore, the natural concentrating function of the gallbladder might amplify the carcinogenic effect of the mediators of carcinogenesis. In addition to S. typhi, certain species of Helicobacter (H. bilis and H. hepaticus) and Escherichia coli have also been implicated in carcinogenesis. As the isolation rate is very poor with the presently available culture techniques, the existence of bacteria in a viable but non-cultivable state is quite likely; therefore, sensitive and specific molecular techniques might reveal the etiological role of bacterial infection in gallbladder carcinogenesis. If bacteria are found to be causing cancers, then eradication of such infections might help in reducing the incidence of some cancers.

Figure 1

Mediators of inflammation and bacterial toxins in carcinogenesis caused by bacteria. ROS: Reactive oxygen species; RNOS: Reactive nitrogen oxide species; iNOS: Inducible nitric oxide synthetase; NF-κB: Nuclear factor-κB; CDT: Cytolethal distending toxin; CNF: Cytotoxic necrotizing factor; BFT: Bacteroides fragilis toxin; CIF: Cycle inhibiting factor; MAP: Mitochondrial associated protein; PMT: Pasturella multocida toxin.