Title: “We are what we eat” Do our cancer cells wear in high
numbers the receptors the viruses used to infect them? Does
Co-carcinogenesis explain most cancers?
Abstract: Cancer cells appear to express the
receptors that reveal the virus that triggered their cancerous tumor
growth. This hypothesis supports Co-carcinogenesis as the cause of
cancer. Co-carcinogenesis is the synergistic actions of a virus and a
carcinogen together on a host cell.
This paper will go through several types of cancer looking
at the patterns of receptors on tumors, of the cancers that tend to appear
together, and looking for the viruses that have been isolated from tumors. The
most likely carcinogen for each cancer will be examined for viral polymerase
inhibiting ability.
Introduction:
Francis Peyton Rous challenged the oncology world
first when he suggested that cancers did not spontaneously occur but could be
triggered by something in a contagious way. Unbeknownst to him he was
working with the Rous Sarcoma virus. (when the virus was discovered it was
named after him) He could see that he was transferring some agent from
one chicken to another and triggering the tumors. The oncology world
seemed to believe that this was strictly a chicken pattern. Unsuccessfully
he alone attempted to isolate viruses from mammalian tumors for years.
In 1933 fellow researcher Richard Shope isolated HPV from
mouse tumors. They now had a mammalian virus. Fervently Rous and his
coworker Friedewald studied the HPV virus attempting to prove that it triggered
the tumors in mammals when combined with carcinogens. In 1944 they published a co-carcinogenesis
paper entitled “ The effect of chemical carcinogens on virus induced rabbit
papillomas.” Rous got the Nobel prize in
1966 for his work on HPV. (1-6)
Co-carcinogenesis suggests that it is the synergistic
actions of a virus and a carcinogen together on a host cell that causes
cancer. Both must be present. However the evidence of viruses can rarely
be found in cancer cells. In petridishes viruses and carcinogens have been shown
to produce cancer cells perhaps because they are merely the triggers of cancer
acting only at the beginning. The oncology world has decided that only
20% of cancers are involved with viruses because they could not find viruses in
the tumors but what if they had been there at the start and the receptors
expressed reflect that.
Based on what we know of tumors, viruses, and receptors this
paper will attempt to show that Rous’s Co-carcinogenesis could explain most of
the cancers we deal with today.
Hypothesis: Cancer cells express receptors that reveal
the virus that triggered their cancerous tumor process. Carcinogens are
present that can inhibit the viral polymerases. This hypothesis supports
Co-carcinogenesis as the cause of cancer.
Evaluation of Hypothesis:
Viruses are now known to make proteins that interact with
the telemores which are the ends of our chromosomes. The condition of the
telomeres, how frayed or pristine, determines how many times the chromosomes
can be copied. Viruses are therefore making our DNA, the cookbooks of our
cells, immortal and open for use. Carcinogens, such as benzene and
phenols, are now known to have multiple actions including inhibiting
polymerases which are the DNA readers. Viruses typically make their own
polymerases which have a stronger affinity for binding in order to compete with
the host's polymerase. Now imagine them coexisting as Co-carcinogenesis
suggests. The DNA has been opened up but the viral polymerases are inhibited
by the carcinogen and a cancer cell has been created. Is this possible?
The virus when it enters a cell uses a specific receptor thus stimulates the
production of more of those specific receptors to be made. It is my
contention that when we look at the cancerous tumors they will be over
expressing the receptor which tells us which virus triggered them. So let's
look at a few cancers and see. (7-11)
Breast cancer has 2 types. An estrogen receptor and non
estrogen receptor type. Interestingly enough 2 viruses have been isolated
from breast cancer; the HPV virus and the Epstein-barr virus. (12)
The Epstein Barr virus is likely using estrogen
receptors. Herpes viruses bind heptad
motifs. Estrogen receptors have heptad motifs.
The pattern of herpes viral infection appears to match that of the
estrogen receptor.
Estrogen alpha receptors cycle to the nucleus which would
allow herpes viruses to interact with the nucleus but in nerves the estrogen beta
receptors cycle to the mitochondria. Herpes viruses are known to hide in
the mitochondria of nerves and to travel down the nerves riding in the
mitochondrias like little cars thus explaining how shingles spreads down
nerves. Using the estrogen receptor would explain how the herpes virus ends up
in different locations. In Breast cancer the herpes virus would be
carried to the nucleus by the estrogen receptor. (11-16)
If the herpes virus Epstein-barr triggers the estrogen
receptor type of breast cancer then the HPV virus could be the trigger of the
estrogen-negative type of breast cancer tumor. Estrogen negative receptor
breast cancers have been found to contain HPV. Inhibition of cannabinoid receptors has shown
to inhibit tumor growth of some breast cancer cells. Are there cannabinoid receptors on these tumors specifically?
Does HPV use cannabinoid receptors? (17, 18)
Cannabinoids inhibited cervical cancer cells migration, a
known HPV cancer. Interestingly enough cannabinus oil has also been a
suggested remedy for non-melanoma cancers. Non-melanoma skin cancer has
associations with HPV. Non-melanoma skin cancer has increased cannabinoid
receptors. Negative- estrogen-receptor-breast cancers and cervical
cancers should be examined for increased cannabinoid receptors. (19-22)
For the two types of breast cancer we can associate two
types of viruses but an increase in receptors is only known for the herpes-
estrogen type. Can we now connect a specific carcinogen to breast cancer?
The carcinogen has to collect at the target tissue which in
this case is the breast. Heptachlor which was an insecticide of the 1980s
and is still currently used on fire ants has been found to collect in the
breast. Since heptochlor is not metabolized and is fat soluble it merely
collects increasing in concentration at the breast until the virus is caught.
Organochlorides have been suspected of triggering breast cancer but
studies seem to indicate the mere collection of the compounds do not cause
cancer. However Co-carcinogenesis could explain the data. (23-24) Does
heptoclor inhibit polymerases?
Chlorine has been shown to inhibit adenovirus DNA
synthesis. If chlorine inhibits the polymerase of the viruses found in
the breast which are HPV and Herpes Zoster then it is highly likely that
heptachlor and the other organochlorides do too. Note that the chlorine in tap
waster is at extremely low levels. Tap water
consumption has been associated with bladder cancers, so the amount of chlorine
added needs to be regulated. The key
here is dose and viruses. Too much at one time could result in the compounds absorbed
in the fatty tissue. (25,26)
The virus culprits for bladder cancer are the polyomaviruses
like BK or hepatitis B. Interesting serotonin receptors are found on bladder
cancers which could be the receptor they are using. (27-29)
Another cancer associated with heptachlor is prostate
cancer. If we look at prostate cancer we find 2 types there too. An
estrogen receptor form triggered by a herpes virus and a melanocortin receptor
form. What virus uses the melanocortin receptor? The flavivirus called
chikungunya virus has been isolated from prostate tumors. Prostate cancer
patients have an increased risk of melanoma, skin cancer. Melanoma cells
over express melanocortin receptors too. Interestingly most people who have
been bitten by a mosquito carrying west nile or other flaviviruses do not
realize they are infected. Flaviviruses could be the cause melanoma. It
is not clear if these melanocortin receptors have been increased in the tumors
of prostate cancers but they have been associated with an increased
proliferation of the prostate cancer cells. (30-33)
Let's look at bone cancers. Each type of bone cancer
has already been associated with a specific virus. Ewings has been
associated with CMV and Epstein barr. Interestingly Ewings has also been
associated with the hormone swings of pregnancy which would elevate estrogen
levels. As herpes viruses they would be using estrogen receptors and the tumors
would have increased estrogen receptors. Chondrosarcoma has also been
associated with estrogen receptors but as a bone cancer of the facial region
the prime suspect should be herpes simplex one. (34-39)
Osteosarcomas are the most common type and largest
group of bone cancers with a higher rate in African males.
Polyomaviruses which includes hepatitis B, the JC virus, mouse polyomavirus,
the rous sarcoma virus of chickens, sv40, and the murine FBJ virus have been
associated with bone cancers. The JC virus being of African origin is found in
slightly higher rates in african americans. Can JC be found in
osteosarcomas? Simian virus 40 specifically has been found in dozens of
osterosarcomas. SV40 infected cells have increased serotonin receptors too.
JC virus was proven to use serotonin receptors which begs the question,
do the serotonin receptors increase with all polyomaviruses? Canine
osteosarcomas have increased expression of serotonin receptors. Serotonin
receptors have also been described as immortalized on osteosarcomas.
Note that gangliosides were originally considered serotonin receptors and that
SV40 uses them. Although gangliosides might be used to gain access to cells
they do not appear to increase in cancers. Polyomaviruses could be using
a serotonin like ligand to gain access to cells but only the serotonin receptor
is apparently increased. (40- )
Spindle cell sarcoma has already been documented and
accepted to be caused by the Rous sarcoma virus. Rous sarcoma viruses are a
type of retrovirus. Retroviruses have also been associated with
gangliosides as receptors. The fact we can see a possible pattern,
association of a virus, with each type of bone cancer is suggestive. It would
be interesting to see if spindle cell sarcomas have increased serotonin
receptors.( -53)
Cadmium is the possible carcinogen for bones it
collects at the growth tip of the bones and has strong associations with the
cancer. Further because teen boys tend to grow rapidly and taller than girls
they would have more cadmium added which could explain why they have higher
rates of bone cancers. Occupations dealing with cadmium have higher rates of
osteosarcoma and heavy metal implants have been found associated with sarcomas.
Cadmium is found in cigarettes, and cigarette smoke. Cadmium can be found with
fertilizers and in Africa the cadmium has been found to contaminate the hot
chocolate of Africa because of this. Cadmium has also been found in
shellfish and oysters in high levels which could explain the clusters of cases
in the northeast coast. Toxic levels of cadmium were also dumped into Tampa Bay
in 2011 and there are clusters there too. Osterosarcoma case clusters
should appear near high cadmium areas. Cadmium can inhibit DNA polymerases directly.
This inhibition fits with our theme of a carcinogen present at the site
which can inhibit the viral polymerases. (55,56)
How about pancreatic cancer? There are 2 types of pancreatic
cancer, exocrine and endocrine. Endocrine cells secrete enzymes into the
bloodstream whereas exocrine cells secrete into the intestine. The exocrine
form is the most common so this must be a common virus. There seem to be
multiple types of endocrine cancers which might match up with the different
viral infections.
First the endocrine pancreatic cancers such as Insulinoma,
Glucogonoma, and gastrinoma duct tumors.
Coxsackie, an enterovirus, has been found in Insulinomas.
Enteroviruses might be using acetylcholine receptors to infect based on
their association with acute flaccid paralysis and acetylcholine secretion.
Mouse insulinomas were found expressing in high number nicotinic
acetylcholine receptors. (57-58)
Serotonin producing endocrine cancers appear to be triggered
by a polyomavirus. Pancreatic duct blocking endocrine tumors have been associated
with serotonin secretion and these same tumors have had Hepatitis B viruses
isolated from them. Hepatitis B as a polyomavirus could be using the serotonin
receptors. Called gastrinomas, these endocrine tumors should be analyzed
for serotonin receptors. Gastrinomas over lap with other parathyroid cancers.
Hepatitis B can infect the parathyroid as well as the liver. (56-60)
Glucagonomas have been associated with necrolytic migratory
erythema.
Glucagonomas have somatostatin receptors expressed.
Merkel cells have been connected with a new polyomavirus and also have
somatostatin receptors expressed. Necrolytic migratory erythema has also
been connected to hepatitis B, another polyomavirus. Are glucagonomas
triggered by merkel polyomaviruses or a similar polyomavirus? (63-68)
The most common pancreatic cancer, adenocarcinomas are the
exocrine pancreatic cancers. Looking at the rest of the exocrine
pancreatic tumors they appear to be over expressing dopamine receptors on their
surfaces. Can the flu virus be found in adenocarcinomas? This is not
known. The flu virus which has also been accused of triggering type one
diabetes seems to be using the dopamine receptors. Diabetes increases the risk
for developing pancreatic cancer and why has been unclear. If viruses trigger
diabetes they could also be there to trigger cancer. Patient history of
both diabetes and alcoholism increases the likelihood of pancreatic cancer even
more. (69-71)
2/3 of pancreatic cancers occur in alcoholics. Alcohol
does inhibit polymerases and could easily inhibit a viral polymerase. The other
pancreatic carcinogen could be N-nitros also known as nitrates or nitrites in
foods. Highly processed foods like meat, cheese, and beer have high quantities
and it's impact has been questioned. Viral polymerases can be inhibited by
nitrogen oxides which nitrates and nitrites are and this feature fits with the
co-carcinogen hypothesis. The influenza replication has been halted by nitric
oxide in mouse models. So does this mean people with the flu should not have processed
meats because of the pancreatic cancer risk? (72-74)
When we look for carcinogens of the brain nitrates, alcohol,
and benzodiazepine are the most likely
candidates. Again, alcohol and nitrates can and do inhibit polymerases
contributing to the stunting of growth and likely inhibits viral polymerases if
they are there. Astrocytes, the nurturing and protecting cells of the
brain’s neurons make up the blood brain barrier. Alcohol is first absorbed by these cells.
Astrocytes are one of the 3 types of glial cells. (75)
Benzodiazepine which
is an anxiety medication can be absorbed into the fats in the brain when in
high concentrations. Benzodiazepine has be proven to inhibit the
polymerases of Hepatits C specifically. The benzene ring of these medications could be what inhibits the
viral polymerases when alcohol is not involved. This is a side effect of an
anxiety drug. (76)
Acyclovir is a medicine prescribed for it's ability
to inhibit the polymerase of herpes viruses and is currently used as a
treatment to stop viral infections. There are cases where herpes encephalitis
was diagnosed, acyclovir was prescribed and then the patient was discovered to
have gliomas tumors. The question is were they misdiagnosed or did the viral
infections become high grade glioma tumors. Acyclovir is not considered carcinogenic
because when fed to rats and mice log term no tumors developed. What if the
rats had herpes infections at the same time? The reason that acyclovir does not
cause cancer in shingles patients has to do with where the virus is.
Herpes viruses use estrogen receptors. The estrogen receptors of nerves
cycle to the mitochondria and use the mitochondria's little DNA. Cancer only
occurs when the virus is at the nuclear DNA which is the huge cookbook. In the
breast or in the glial cells of the brain acyclovir would be a carcinogen and
should never be used in those cases. (77,78)
Gliomas, brain cancers of glial cells, are also
associated with Alzheimer's disease. If some forms of Alzheimer's are due to a
herpes virus infecting and destroying a neuron's mitochondria then could
gliomas be the herpes virus infecting the nucleus of the glial cells when the
carcinogen such as nitrates or alcohol are there? The overlap of the
gliomas and Alzheimer's is the herpes virus. Herpes simplex virus encephalitis
has been found in glioma patients. Cmv, another type of herpes virus, has also
been connected to gliomas especially in children. Herpes zoster has been
connect to gliomas too. With all the connections to herpes viruses it is not
surprising that some gliomas express estrogen receptors. (79-85)
Shingles, which is the emerging of herpes zoster, has
already been shown to be a risk factor for stroke. Could this be the herpes
zoster starting to infect the astrocyte glial cells of the blood brain barrier?
Is stroke a risk factor for glioma? Should people refrain from drinking after
strokes to prevent glioma? (86-88)
Meningiomas are the brain cancers of the meninge cells which
are the connective tissue cells between the brain and the skull. Meningiomas
are associated with polyomaviruses like sv40. Meningiomas have somatostatin
receptors not estrogen receptors expressed.
Again the virus and the receptors expressed are matching up. (89,90)
As for my original carcinogen example of simple benzene, it
has been associated with Leukemia when consumed, which means it goes to the
bone marrow. Viruses that infect the bone marrow like respiratory
syncytial virus have been associated with the disease too. Children with
acute lymphoblastic leukemia have often been exposed to RSV in the first nine
to 12 months of life. Was it a combination of RSV and benzene exposure? Benzene
appears in the waste water of fracking and could be contaminating the well
waters of people living near them. (91-93)
Respiratory syncytial virus, measles and mumps as
paramyxoviruses could be using Nectin 4 as a receptor to enter cells.
Ovarian cancer has over expressed Nectin 4 receptors. Interestingly
enough measles was once considered to be protective against ovarian cancer. Is
this because a paramyxovirus actually infects the ovary triggering the ovarian
cancer? Inflammation of the ovary is a symptom of the measles, which makes
sense because it has Nectin 4. Could measles vaccines as a paramyxovirus
protect against the RSV? (94-97)
The carcinogen of ovarian cancer is asbestos or talc powder.
The asbestos fibers have been found in the ovaries and fallopian tube of
asbestos workers correlating with the increased rates of ovarian cancer but
what about the use of talc? The association of talc has not been proven but is
suspected. (98-101)
There is not enough evidence to prove that cancers wear the
receptors that the viruses used to infect them but there is enough to
investigate the possibility. With luck this will prove Co-carcinogenesis and we
can prevent cancer with vaccines. Assuming we figure out how to make vaccines
for all of these viruses. One can only hope.
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