The Parasite-Cancer Connection
There is a huge neglected area affecting human health today and one few people like to talk about; parasitic infections.
Each year there are an estimated 3.8 billion reported cases of infections from parasites, largely from raw foods such as fish and vegetables aswell as from contaminated fresh waters occupied by snails in areas of Africa, Asia and the Middle East. Increasing studies are now showing that these parasites have the ability to change the hosts immune system to allow their eggs to survive, but could these changes of the immune system and their persistence result in a loss of the body’s ability to control cancer cells?
The causes of cancer still remain mysterious to most of us, even to many scientists. Most recently the areas of the causes from the somatic mutation theory where cancer is derived from a single somatic cell that has accumulated multiple DNA mutations, to the more recent theory of metabolic disease, where the cancer cell metabolism shifts away from a normal Oxidative phosphorylation (OXPHOS) process of energy conversion towards anaerobic glycolysis and very inefficient energy process as an alternative metabolic reprogramming, known as the Warburg effect (Warburg, 1956) .
These technical explanations may go some way to explain how cancer cells progress and establish themselves, but they don’t help us understand how the are initiated, so what actually starts the process?
There have been many other explanations of what can start a mutational process; a toxic overload from a carcinogen, a hormonal imbalance, a DNA Telomeric error, a very poor diet, a high stress traumatic event, which I am quite sure are contributory factors but they don’t quite explain the aggressive nature of cancer oncogenesis and why many tumor suppressors are mutated or deleted to facilitate the survival of mutant cells and why they escape the immune system and their elimination. Or rather what is also altering the immune system to enable their survival whilst jeopardising the life of the host?
Worldwide Increase in Infections from Parasites
According to Harvard School of Public Health, infections may be responsible for over 15% of all malignancies worldwide. Important mechanisms by which infectious agents may induce carcinogenesis include the production of chronic inflammation, the transformation of cells by insertion of oncogenes and inhibition of tumour suppressors, and the induction of immunosuppression. Common characteristics shared by infectious agents linked to malignancies are that they are persistent in the host, often highly prevalent in the host population and induce cancer after a long latency, sometimes up to 30 years.
Cancers are characterised by uncontrolled growth of abnormal and transformed cells, which can invade adjacent tissues, but fortunately the body possesses a sophisticated ability to self-correct by detecting an intruder and to digest it with macrophages. We all have slightly faulty DNA and in response to environment , toxins and chemicals; mutant cells are created all the time but a fully functioning immune system is constantly on the lookout for these unproductive cells and will release macrophages to literally consume them and recycle the materials.
Macrophages (Big Eaters) are one of the most widely distributed innate immune cells and present essential roles in the primary response to pathogens, maintenance of tissue homeostasis, inflammation, and immunity, they are a type of white blood cell, of the immune system, that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface, however it appears they can be hijacked by highly advanced pathogens.
The body also possesses tumor suppressors to prevent runaway cell growth such as P53, Rb, (p16)INK4a/ARF, RASSF1, FHIT which are there to defend us from mutant cells which have lost their regulation and need to be destroyed, however, tumor suppressors have been shown to be modulated by macrophages using (TGF)-ß, IL-10, VEGF and the disabling of natural killer (NK) cells, differentiation of CD4+ T cells into Th2 cells(Yang, which is Tumor promoting), and inhibition of the CD8+ T cells anti-tumoral activity, but what is initiating this?
Disruption of the p53 and Rb tumor suppressor pathways is a fundamental trend of most human cancer cells, in fact p53 is directly targeted in approximately 50% of human malignancies (ref.), other mechanisms are required to shut down the p53 pathway in tumors with wild-type p53. For example, lesions in the MDM2 gene such as amplification can lead to MDM2 overexpression. In tumorigenesis, loss of Rb (Retinoblastoma Protein) function can occur by direct inactivation of the Rb gene itself through mutation, sequestration of the Rb protein by viral oncoproteins, or promoter hypermethylation or by deregulation of the genes controlling Rb phosphorylation status. (ref.)
What makes this compelling as a more frequent cause of Cancer than it currently is regarded (approximately 5% of cancers in the western world), are the particular genes being upregulated (oncogenes) and the tumor suppressors which are being altered, they are genes familiar in the phenotype of particular common cancers. https://www.ncbi.nlm.nih.gov/pubmed/10971784?dopt=Abstract
Hi-jacking The Immune System
In most tumors, Tumor Associated Macrophages (TAMs) show properties of an alternative polarisation phenotype (M2) characterised by the expression of a series of chemokines, cytokines, and proteases that promote immunosuppression, tumor proliferation, and spreading of the cancer cells through a reduced immune response, helpful eh? Tumor suppressor genes have been traditionally linked to the regulation of cancer progression; however, a growing body of evidence indicates that these genes also play essential roles in the regulation of innate immunity pathways.
TAMs exert immunosuppressive functions through the release of anti-inflammatory cytokines, modulate the tumor microenvironment producing survival/growth factors (e.g., vascular endothelial growth factor, VEGF), and facilitate the progression of tumors via proangiogenic factors release. Studies have shown that in the early stages of schistosomiasis, the host immune responses are of the Th1-type (M1) with liver inflammation, which shifts to Th2-associated immune suppression (M2) in response to the parasite eggs, resulting in the secondary liver fibrosis.
Another process in which TAMs have been involved is in the regulation of metastasis. Indeed, a correspondence between the number of macrophages in metastatic sites and the metastatic potential of the tumor has been observed , and systemic depletion of macrophages results in reduced formation of lung metastases . These findings are in line with clinical studies showing that increased numbers of macrophages in regional lymph node metastases correlates with poor patient survival .
TAMs appear to influence the micro-environment to facilitate migration of tumor cells by the release of MMPs, for example, MMP-2, MMP-7, MMP-9, IL-23 and IL-10. MMP’s are enzymes that in concert are responsible for the degradation of most extracellular matrix proteins during organogenesis, growth and normal tissue turnover. Those MMPs contribute to transform the proteins of the extracellular matrix and induce the expression of lymphatic endothelial growth factor (VEGF-C), events that promote dissemination of tumor cells by stimulating the formation of lymphatic vessels in tumors. (ref.)
So the macrophages are mean’t to be working for us to keep damaged cells from developing into cancer cells, but now we know that our macrophages are being used to help cancer cells grow and evade destruction. Macrophages in the blood can be hijacked by parasites found in our blood, such as the very common blood and liver fluke. Their interactions with the host and parasite-derived products including their eggs can strongly induce carcinogenesis.
How Do The Infections Happen?
There is a common belief that parasites occur only in less developed countries, where poverty and unclean living are more commonplace. However, the presence of parasites is not confined to these conditions and, despite the popular misconception, those living in the developed world are also at risk Most parasites in humans are cosmopolitan. The most common symptoms include:
Diarrhoea, constipation, irritable bowel, cramps, bloating,
Malabsorption, mucus, fatigue, nausea,
Skin rashes, dry coughs, brain fog, dermatitis,
Lymph blockages, joint pain, memory loss, headaches.
The parasite enters humans after the ingestion of freshwater raw fish (containing infective stage cercariae), bathing or wading in contaminated waters, or eating raw unwashed contaminated vegetables and travels to the liver bile duct where a liver fluke can live in a human for up to 30 years. Other parasites such as the whipworm Trichiuris trichiuria from soil found in Europe, can live in the human body for up to 10 years. Most worms tend to create malnourishment in the host, but the trematodes Opisthorchis viverrini (liver fluke), Clonorchis sinensis (liver fluke) and Schistosoma haematobium (blood fluke) are classified as Group 1 biological carcinogens and are the most common types of helminth found in human infections.
The fluke parasite usually inhabits the intrahepatic bile ducts of humans, but on occasion the pancreatic duct and gallbladder. From this position, the liver fluke lays eggs that enter the biliary system and are excreted in the faeces, to be ingested by Bithyniasnails, the first intermediate hosts. (ref.)
Testing for the presence of these parasites involves: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233816/ (Brindley et al., 2015). https://www.ncbi.nlm.nih.gov/pubmed/26618199
People become infected when larval forms of the parasite, released by freshwater snails, they penetrate human skin in contaminated water. In the body, the larvae develop into adult worms, which live in the blood vessels and release eggs.
|Disease||Human infections||Annual deaths|
|All worms||4.5 billion|
|Ascaris||1.0 billion||20 thousands|
|Hookworms||900 million||50-60 thousands|
|Schistosomes||200 million||0.5-1.0 million|
Some of the eggs are passed out of the body to continue the parasite’s lifecycle. Others become trapped in body tissues, causing damage to organs and altering our genes to allow their new habitation. https://www.bbc.co.uk/news/science-environment-39928036
Not so long ago, human diseases caused by parasitic worms were thought to be confined to resource poor communities throughout Africa, Asia and South America. But in this age of global travel and changing climate, parasitic worms are slowly but surely moving into parts of Europe and North America. The long-term consequences of increased parasitic worm distributions are difficult to predict, but the harm that infection causes highlights the need for developing control strategies that can mitigate this 21st-century threat to global health.
Schistosomes are parasitic helminths that infect humans through dermo-invasion while in contaminated water. Schistosome infections occur in 74 developing tropical and subtropical countries in which over 200 million people are infected. Of those, 120 million patients show symptoms with 20 million severely infected.
What has not been fully elucidated is the possibility that these organisms could be being picked up while on holiday, with minimum or no symptoms and lie dormant waiting for the opportunity such as a stress event when the immune system is weakened and then make it’s move to fully disable the host immunity within the blood by infecting the macrophage which allows mutating cells that would normally be destroyed to go unchecked and allow them to grow unchallenged. So cancer and tumors are actually a by-product rather than an intention of the fluke parasite.
It’s not uncommon for people to come back from a tropical holiday with an illness, but what if we pickup and infection where there are no symptoms as in the case of blood and liver flukes?
While considering this possibility, I tried to investigate whether schistosomes exist in ponds and lakes of the UK. That being the case, our household animals who may dash through ponds and lakes etc, could expose us to these pathogens. Dependent on the incubation time and a host of other factors, such as stress and toxicities which create conditions for illness, we may not readily connect the infection with a later cancer development once the pathogen grows large enough to lay eggs, which is where the cancers tend to develop as the tumor suppressors and immune macrophages are deactivated.
Organic & Raw Foods and The Increase in Soil Transmitted Helminths (STH)
Hazards of parasitic infection are not just confined to contracting a parasite while on a tropical holiday, we can also find them in the UK in the soil and from our pets. The increase in eating organic vegetables has seen an increase in infections from a number of soil helminths such as Trichiuris trichiuria, figures which show that almost a billion infections per year from this common parasite.
The intake of organic vegetables, the end of national control activities, and the immigration from endemic areas especially from tropical countries is showing signs in the prevalence of soil transmitted helminths. People who worry about pesticides in food which can be linked to many diseases often tend to prefer organic and raw foods, despite the high cost. The belief that raw foods contain more nutrients means that the a parasitic infection is more likely.
What if You already Have Cancer?
Infections may be responsible for over 15% of all malignancies worldwide. Important mechanisms by which infectious agents may induce carcinogenesis include the production of chronic inflammation, the transformation of cells by insertion of oncogenes and inhibition of tumour suppressors, and the induction of immunosuppression. Common characteristics shared by infectious agents linked to malignancies are that they are persistent in the host, often highly prevalent in the host population and induce cancer after a long latency.
People who have active cancers such as Liver, Bile Duct, Colon, Rectal, Breast, Bladder, Stomach and Pancreas would benefit from screening for parasite presence in stool (macroscopic test) Urine or blood. It would seem reasonable to either test for parasite infections in the case of active cancers or to take a precautionary anti-parasitic approach with herbals until able to confirm the actual type of parasite present. Such herbals can include; Garlic, Black Walnut, Pumpkin Seed Oil, Myrrh, Wormwood, Oregano, Zinc, Berberine, Mastic Gum, Rhizome Rhei, Artemesinin, Curcumin, Peppermint and Rhubarb root. Starting with a biofilms disruptor can make treatment more successful because many of the parasites can protect themselves under a layer of biofilm.
Some herbal anti-parasite items available are:
Pathogest (biofilms disrupter) Best taken 30 mins before the main anti-parasitic.
H-Pylorid (not just for HPylori)
Paranil (wide-spectrum anti-parasitic capsule)
Monolaurin (coconut-based anti bacterial).
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