Did you know that cancer is the 2nd leading cause of global mortality after cardiovascular diseases? Cancer can be linked to unhealthy lifestyle choices (such as lack of appropriate exercise or an excess in consumption of tobacco and alcohol) but also with exposure to dangerous carcinogens(such as pollutants, pesticides, UV radiation or the inhalation of asbestos), and even genetic factors. The appearance of cancer has also been attributed to viral infection. For example the papillomavirus leading to uterine cancer. Few people know that bacteria can also be associated with cancer. Despite the mounting evidence in scientific literature that shows that microorganisms play a significant role in either the initiation or the progression of tumors, it is uncommon to attribute cancer with the presence of bacteria even within the scientific community.
Since the beginning of 2021, I have been working on bacterial toxins suspected to initiate or accelerate the progression of tumors. I have had the occasion to work with data from clinical studies in hospitals and was particularly taken by the development of new anti-cancer treatments and the identification of novel biomarkers that may signal the presence of cancerous cells. To better understand the mechanisms responsible for the origin of cancer will allow us to better treat these diseases. Therefore, today I would like to share a little of my work with you all.
The link between bacterial infection and cancer
Like viruses, bacteria are invisible to the naked eye, and there exist many species that do not provoke sickness while others are responsible for disease. Unlike viruses however, bacteria do not need to enter host cells to be able to replicate.
In the early 80's, two Australian pathologists, Barry Marshall and Robin Warren, identified the bacterial strain Helicobacter pylori in the stomach of patients suffering from gastritis. Gastritis is defined as inflammation of the stomach and can further progress into cancer and gastric ulcers 1. The novel connection between bacteria and stomach disease shook the scientific community, and Warren and Marshall were awarded the Nobel Prize in Physiology and Medicine in 2005 for their work.. Not only did this discovery prove that the stomach was not a sterile environment, it also proposed a link between bacteria and gastric disease for the first time 2. Patients that carry these bacteria have a higher risk of developing certain cancers. Ever since this association was made, more and more studies show strain-specific association between bacteria and cancer.
Cancer is caused by mutation
How can we explain this link between bacteria and cancer? To understand in greater detail, we must keep in mind the conditions of tumor formation: accumulation of mutations that affect regular cellular processes. A normal cell has a limited capacity to proliferate, and will eventually die. On the other hand, a cancer cell can proliferate indefinitely without death due to its mutations.
These critical mutations appear when the cell’s DNA is damaged and not correctly repaired. The DNA sequence is therefore changed and does not code for the same information, altering normal cellular function. These events are random, but their frequency can be increased by environmental, behavioral, genetic factors, or the presence of viral or bacterial infection 3.
How bacteria can cause cancer
Our bodies are continuously exposed to bacteria, both dangerous and benign. In most cases, these omnipresent bacteria pose no problems and co-exist with our bodies, while our bodies maintain a barrier that stops these bacteria from entering into our tissues. However, this barrier can weaken and break under certain conditions such as an injury, infection by other pathogenic bacteria, or genetic factors 4.
In these situations, bacteria can directly interact with our cells behind this barrier. Some bacteria secrete toxins that lead to DNA damage and subsequent DNA mutations. Some interfere with cellular processes, for example by enhancing cellular proliferation or survival. Others may induce a chronic inflammatory response that may also lead to DNA mutations.
The clinical relationship between bacteria and cancer
Pro-cancer activities of certain bacterial strains have clearly been demonstrated, often in cell culture and then also in animal models. From epidemiological studies, these bacteria have also been found in cancer patients where they are absent in healthy subjects.
However the relationship between cancer and bacteria is still not completely clear. It is often difficult to determine if the presence of bacteria is directly related to the initiation of cancer development. It is possible that the presence of certain bacteria in cancer patients is not directly linked to their disease. It is important to note that certain bacterial strains only proliferate effectively under conditions that are strain-specific. The presence of tumors could offer environments that are more suited to certain bacteria that then take advantage of such newly available habitats. Whether opportunistic or agonistic, bacteria are potential new biomarkers to be explored in cancerology. If certain bacterial strains are present in large quantities during certain types of cancer, it may be possible that the detection of these bacterial strains may indicate the presence or risk of cancer (5). As certain types of cancer, particularly in early stages, are difficult to identify, these novel biomarkers may allow medical professionals to identify cancer cells early begin treatment rapidly, and potentially improve their livelihood.
References
1. Warren, JR et al. (1983) Unidentified curved bacilli on gastric epithelium in active chronic gastritis. Lancet. https://doi.org/10.1016/S0140-6736(83)92719-8
2. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. (1994) Schistosomes, liver flukes and Helicobacter pylori. IARC Monogr Eval Carcinog Risks Hum.
3. Organisation mondiale de la Santé (2022) Cancer https://www.who.int/fr/news-room/fact-sheets/detail/cancer
4. Garrett, WS. (2015) Cancer and the microbiota. Science. https://doi.org/10.1126/science.aaa4972
5. Gagnière, J et al. (2016) Gut microbiota imbalance and colorectal cancer. World J Gastroenterol. https://doi.org/10.3748/wjg.v22.i2.501
This article was specialist edited by Dr Eliette Touati, copy edited by Dr Marie Juzans and translated by Kodie Noy.
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