Possible strategies of bacterial involvement in cancer development

Abstract

Infections have been implicated in around 18% of all malignancy in humans. The common infections include viruses, bacteria and Schistosomes. The role of bacteria in carcinogenesis is now quite evident particularly in H. pylori induced gastric cancer and mucosa associated lymphnoid tissue (MALT) lymphoma and Salmonella typhi causing carcinoma gallbladder. The chronic inflammation is the important mechanism involved in the majority of bacteria induced malignancies. The chronic inflammation is mediated by various pro and anti - inflammatory cytokines including IL-1, IL-6, IL-17, TNF-α and IL-10. The key factor in the inflammatory process is the activation of NF-kB. Various toxins are produced by different bacteria which cause direct damage to the host cells by DNA damage or affecting DNA repair mechanism resulting in alteration in the enzyme transcription or translation. It has also been postulated that bacterial infection activate inflammatory/immune cells to generate reactive oxygen species (ROS) and reactive nitrogen species (RNS) which causes DNA damage leading to cancer. The free radicals generated also acts at different levels which affects the cellular homeostasis. The epigenetic alteration in form of DNA methylation and histone modification has also been reported in bacteria induced carcinogenesis. The other alternative molecules has been evolved by the bacteria that involved in adhesions of bacteria to cell surfaces, modulation of cytoskeleton or junctional activities and affecting specific signaling pathways. The studies have shown that bacterial infection also causes immune modulation and result in persistence of the infection. It is also seen that not only the bacterial pathogen but the host genetic factors also determine the susceptibility and persistence-of infection. The certain genotypes of inflammatory mediators are associated with increased risk of cancer. Thus, the bacteria induced carcinogenesis is a multifaceted, complex process.