Carcinogenic bacteria

Cancer bacteria are bacteria infectious organisms that are known or suspected to cause cancer. While cancer-associated bacteria have long been considered to be opportunistic (i.e., infecting healthy tissues after cancer has already established itself), there is some evidence that bacteria may be directly carcinogenic. Evidence has shown that a specific stage in cancer can be associated with bacteria that is pathogenic. The strongest evidence to date involves the bacterium H. pylori and its role in gastric cancer.

Oncoviruses are viral agents that are similarly suspected of causing cancer.

Helicobacter pylori colonizes the human stomach and duodenum. It is described as a Class 1 carcinogen. In some cases it can cause stomach cancer and MALT lymphoma. Animal models have demonstrated Koch's third and fourth postulates for the role of Helicobacter pylori in the causation of stomach cancer. The mechanism by which H. pylori causes cancer may involve chronic inflammation, or the direct action of some of its virulence factors, for example, CagA has been implicated in carcinogenesis. Another bacteria that is in this genus is Helicobacter hepaticus, which causes hepatitis and liver cancer in mice.

Chronic inflammation contributes to the pathogenesis of several types of malignant diseases, but it is particularly important for H. pylori. Following a H. pylori infection many circulating immune cells are recruited to the infection site including neutrophils. To destroy the pathogens, neutrophils produce substances with antimicrobial activities such as oxidants like reactive oxygen species (ROS) and reactive nitrogen species (RNS). H. pylori can survive the induced oxidative stress by producing antioxidant enzymes such as e.g., catalase. However, the overproduction of ROS and RNS induces various types of DNA damage in the infected gastric cells.At the same time H. pylori is known to down-regulate major DNA repair pathways. As a result, genomic and mitochondrial mutations accumulate, leading to genomic instability - a well-known hallmark of Cancer - in the gastric cells.

The virulence factor CagA in H. pylori has been linked to the development of gastric cancer. Once CagA is injected into the cytoplasm it can change the gastric cell signaling in both a phosphorylation-dependent and -independent manner. Phosphorylated CagA affects cell adhesion, spread and migration but can also induce the release of the proinflammatory chemokine IL-8. Additionally, interactions of the CRPIA motif in non-phosphorylated CagA were shown to lead to the persistent activation of the PI3K/Akt pathway, a pathway that is often overly active in many human cancers. This leads to the activation of the pro-inflammatory NF-κB and β-catenin pathways as well as increased gastric cell proliferation. Furthermore, CagA has also been found to increase tumor suppressor gene hypermethylation and thereby inhibiting the tumor suppressor genes. This is achieved by upregulating the methyltransferase DNMT1 via the AKT–NF-κB pathway. Lastly, CagA also induces the expression of the enzyme spermine oxidase (SMOX) that converts spermine to spermidine. As a by-product H₂O₂ is produced which causes ROS accumulation and contributes to the oxidative stress that the gastric cells experience during chronic inflammation.

A number of bacteria have associations with cancer, although their possible role in carcinogenesis is unclear.

Salmonella Typhi has been linked to gallbladder cancer but may also be useful in delivering chemotherapeutic agents for the treatment of melanoma, colon and bladder cancer. Bacteria found in the gut may be related to colon cancer but may be more complicated due to the role of chemoprotective probiotic cancers. Microorganisms and their metabolic byproducts, or impact of chronic inflammation, may also be linked to oral cancers.

The relationship between cancer and bacteria may be complicated by different individuals reacting in different ways to different cancers.