Bacterial infection as a cause of cancer.

Abstract

Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Helicobacter pylori infection. H. pylori has been epidemiologically linked to adenocarcinoma of the distal stomach by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds. H. pylori is the first bacterium to be termed a definite cause of cancer in humans by the International Agency for Research on Cancer. Mutagenic bacterial metabolites are also suspected to increase risk for cancer. This model is best exemplified in colon cancer. Bile salt metabolites increase colonic cell proliferation. Exogenous compounds such as rutin may be metabolized into mutagens by resident colonic flora. Moreover, Bacteroides species can produce fecapentaenes, potent in vitro mutagens, in relatively high concentrations. In vivo data on human carcinogenesis by bacterial metabolites, however, are inconsistent. Local bacterial infections may also predispose to nonnodal lymphomas, although the mechanisms for this are unknown. Gastric lymphomas and immunoproliferative small intestinal disease have been most strongly linked to underlying bacterial infection. Because bacterial infections can be cured with antibiotics, identification of bacterial causes of malignancy could have important implications for cancer prevention. -Environ Health Perspect 1 03(Suppl 8): 263-268 (1995)

Intestinal Bacteria Modify Lymphoma Incidence and Latency by Affecting Systemic Inflammatory State, Oxidative Stress, and Leukocyte Genotoxicity

“…Our results and others demonstrate that oral administration of L. johnsonii reduces both oxidative stress (40, 41) and systemic genotoxicity (this study). Mechanistically, there are precedents that microbial environments modulate cancer formation in part through oxidative stress mediated by inflammatory or carcinogenic bacterial metabolites on local epithelial cells (15, 42). For example, inflammation that accompanies H. pylori infection, S. haematobium infection, or human inflammatory bowel disease is associated with elevated risk of stomach, bladder, or colon cancer, respectively (42).…”

“…Mechanistically, there are precedents that microbial environments modulate cancer formation in part through oxidative stress mediated by inflammatory or carcinogenic bacterial metabolites on local epithelial cells (15, 42). For example, inflammation that accompanies H. pylori infection, S. haematobium infection, or human inflammatory bowel disease is associated with elevated risk of stomach, bladder, or colon cancer, respectively (42). In an experimental system examining vaginal infection of mice with the bacterium Gardnerella vaginalis , oral administration of L. johnsonii reduced levels of proinflammatory cytokines, oxidative stress (iNOS), and activation of NF-kB (41).…”

Bacterial Infection Promotes Colon Tumorigenesis inApcMin/+Mice

“…Infection with the bacterium Helicobacter pylori is a risk factor for gastric cancer [9]. H. pylori infection is known to cause chronic inflammation and to increase epithelial cell proliferation in the stomach.…”

Detecting Phenotype-Specific Interactions between Biological Processes from Microarray Data and Annotations

“…As one major type of interspecies interactions, infection happens when a foreign species (for instance, virus, or bacterium) invades a host organism (say, human) and interferes with its normal functioning, which may lead to severe diseases and cancer [41]. Parasitic bacteria species, such as Toxoplasma gondii (cause of Toxoplasmosis), were known to inhibit the apoptosis of infected host cells possibly by interfering with the caspase cascade, therefore increasing their survival opportunity [42].…”