Is cancer a genetic or metabolic disease?

The prevailing paradigm is that cancer is a genetic disease caused by somatic mutations occurring in the course of cell division. However, it has been know for many years, ever since Otto Warburg’s effect has been discovered, that cancer cells favor a less efficient metabolism via glycolysis rather than the much more efficient oxidative phosphorylation pathway even in the presence of sufficient oxygen.

The alternative theory to somatic mutations as the culprit of cancer is that most cancers are metabolic diseases caused by dysfunctional mitochondria and mutations occurring in nucleus are the effect of metabolic instability of the cell. It follows that cell machineries in charge of normal cell growth suffer mutations leading to proliferation rather than the other way around.

The following experimental evidence points to conclusions that the many genetic mutations associated with cancers (over 11.000 mutations have been associated with colon cancer alone) have almost no effect on cancer as long as fully functional mitochondria (s) are present in the cell…

The experiments have shown that transplanting of tumor nucleus into cell with normal cytoplasm does not produce cancer cells. Transplanting of normal nucleus into cells with tumor cytoplasm produces tumor cells.
How could these facts be reconciled with the predominant theory that somatic mutations are the cause of great majority of cancers?

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19 thoughts on “Is cancer a genetic or metabolic disease?

  1. The only thing I can contribute on cancer is that decay is behind its increase. If people did not decay they would not get cancer. in fact all people would eventually get cancer if we outlived other things that kill us. Then i understand ethnic groups have more cancer then others or rather more types of cancer.

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  2. Robert Byers: The only thing I can contribute on cancer is that decay is behind its increase.

    Experts like Dr. Seyfried say the great majority of cancers can be prevented by keeping mitochondria (s) healthy. How? Therapeutic fasting and ketogenic diet..

    Seyfried also says that entropy can lead to genomic instability.

    Nobody really dies of old age or decay. These often lead to organ or systemic failures…

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  3. Hi J-Mac
    My understanding is that cancer is caused by accelerated stem cell division in mature cells. This happens when embryonic pathways get up regulated. The up regulation occurs when the protein destruction mechanism which is part of the ubiquitin system gets turned off. This can be caused by.
    -imbalance of hormones
    -a mutation causing the ubiquitin system to not operate properly.
    If this happens a possible stop gap to prevent a tumor forming is apoptosis and this is where mitochondria may be involved.

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  4. colewd: My understanding is that cancer is caused by accelerated stem cell division in mature cells. This happens when embryonic pathways get up regulated. The up regulation occurs when the protein destruction mechanism which is part of the ubiquitin system gets turned off.

    Hi Bill,
    My understanding is that any mutations happening during embryo development are the most likely to be lethal forcing the embryo to abort…
    This brings us to the problem of evolutionary mechanism: if one kind of animal were to evolve into another kind, the mutations would have to happen early on during embryo development for any body plan changes to take place. But those mutations are usually most damaging leading to developmental issues or abortion…

    BTW: Dr. Seyfried talks about mutations in embryo development in one of his videos. When I find it, I will attach the link.

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  5. J-Mac,

    My understanding is that any mutations happening during embryo development are the most likely to be lethal forcing the embryo to abort…

    I have heard this also. In addition mutations to key cellular processes like splicing seem to be rare and often lethal.

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  6. J-Mac: Experts like Dr. Seyfried say the great majority of cancers can be prevented by keeping mitochondria (s) healthy.How? Therapeutic fasting and ketogenic diet..

    Seyfried also says that entropy can lead to genomic instability.

    Nobody really dies of old age or decay. These often lead to organ or systemic failures…

    The decay is from old age and this decay ruins the biology and so stuff malfunctions.
    I wish diet and fasting worked but this surely is incompetent advice from this person.

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  7. colewd:
    J-Mac,

    In addition mutations to key cellular processes like splicing seem to be rare and often lethal.

    Unless they are preprogrammed, just like in case of metamorphosis…The question still remains: where is the information preprogrammed as the great majority of it is not in DNA?

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  8. Robert Byers: The decay is from old age and this decay ruins the biology and so stuff malfunctions.

    And the old age from decay.? Thanks Bob!

    Robert Byers: I wish diet and fasting worked but this surely is incompetent advice from this person.

    The calorie restricted diet, which includes fasting and ketogenic diet, reversed aging and decay in mice experiments…

    In humans, short and long term studies have showed the slowing down or even the reversal of many diseases often associated with aging, such as Alzheimer’s, Parkinson’s, dementia, cancer, diabetes, atherosclerosis…
    While the process of aging can’t be reversed permanently, many of its effects can be slowed down or even reversed leading to better quality of life in old age and often to longer life…

    https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30605-1

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  9. “NON-MUTAGENIC ORIGIN OF METASTATIC BEHAVIOR

    Recent studies from Brook Chernet and Michael Levin have shown that alterations in bioelectric membrane signaling can produce the metastatic behavior of Xenopus melanocytes in the absence of somatic mutations, which further suggests that the tumorigenic phenotype is not dependent on nuclear gene mutations (43,44). In other words, nuclear gene mutations alone are insufficient for producing tumors, whereas the tumorigenic phenotype can be produced in some cells without nuclear mutations.

    THE ABSENCE OF GENE MUTATIONS IN CANCER CELLS

    The SMT is based on the premise that nuclear gene mutations are responsible for the dysregulated division of cancer cells. Stuart Baker, however, has reviewed gene sequencing studies that failed to detect any pathogenic somatic mutations in several types of cancers (45). Michael Kiebish et al. also found no pathogenic mutations in mitochondrial DNA from five independently derived mouse brain tumors (46). Moreover, Donald Williams Parsons et al. could find no mutations in any of the three signaling systems of sample Br20P that was obtained from aggressive glioblastoma (47).

    CANCER DRIVER GENES FOUND IN NORMAL CELLS

    Recent studies show that normal cells in various tissues contain cancer driver genes. Inigo Martincorena and his team recently found large numbers of cancer driver genes in normal human skin (48,49). Indeed, the prevalence of NOTCH1 mutations in normal esophagus tissue was several times higher than in esophageal cancers. Somatic driver mutations found in brain tissue have been linked to psychiatric disorders rather than to cancer (50). These findings are concerning given that new immunotherapies could target driver mutations in normal cells as well as in tumor cells (48). Significant adverse effects involving inadvertent targeting of normal tissue cells have already been seen in some patients treated with immunotherapies (51).”

    https://www.crossfit.com/essentials/is-cancer-a-genetic-or-metabolic-disease-part-5

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  10. “Cancer progression is more consistent with Lamarckian than Darwinian evolution

    When viewed as a mitochondrial metabolic disease cancer progression is more in line with the evolutionary theory of Lamarck than with the theory of Darwin (20). Many investigators in the cancer field have attempted to link the Darwinian theory of evolution to the phenomenon of tumor progression (171–174). The attempt to link cancer progression to Darwinian evolution is based largely on the view that nuclear somatic mutations are drivers of the disease. According to Lamarck’s theory, it is the environment that produces changes in biological structures (175). Through adaptation and differential use, these changes lead to modifications in the structures. The modifications of structures would then be passed on to successive generations as acquired traits. Lamarck’s evolutionary synthesis was based on his belief that the degree of use or disuse of biological structures shaped evolution along with the inheritance of acquired adaptability. Lamarck’s ideas could also accommodate a dominant role for epigenetics and horizontal gene transfer as factors that could facilitate tumor progression (176,177). In addition to nuclear epigenetic events involving acetylation and phosphorylations, mitochondria are also recognized as a powerful extra nuclear epigenetic system (159,178–180). Other epigenetic phenomena such as cytomegalovirus infection, cell fusion and horizontal gene transfer can also contribute to cancer progression and metastasis (147,159,181–184).”

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3941741/#!po=36.8852

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  11. Can you two nutbags go waste your time doing something else instead of potentially getting people killed by spreading fad-diets and crackpottery? The place for this debate to be had is in the peer-reviewed literature between qualified experts, and from this the conclusions of correctly applied scientific methodology and testing can translate into clinical actions.

    Your intentions may be good, but you are not qualified to give people cancer-treatment advice, much less debate how it works or can be cured.

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  12. Rumraket:
    Can you two nutbags go waste your time doing something else instead of potentially getting people killed by spreading fad-diets and crackpottery? The place for this debate to be had is in the peer-reviewed literature between qualified experts, and from this the conclusions of correctly applied scientific methodology and testing can translate into clinical actions.

    Your intentions may be good, but you are not qualified to give people cancer-treatment advice, much less debate how it works or can be cured.

    And yet, those of us unfamiliar with all this molecular biology are inundated with claims that “X causes cancer”, whether X is Roundup, smoking, asbestos, or whatever from a long and growing list. So it would seem that there are foods, chemicals, behaviors etc. that DO make cancer more likely and that we should therefore avoid as much as possible. It seems sensible to pay attention to these claims, even if we can’t understand what these things are doing to us at the cellular level.

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  13. Flint: And yet, those of us unfamiliar with all this molecular biology are inundated with claims that “X causes cancer”, whether X is Roundup, smoking, asbestos, or whatever from a long and growing list. So it would seem that there are foods, chemicals, behaviors etc. that DO make cancer more likely and that we should therefore avoid as much as possible. It seems sensible to pay attention to these claims, even if we can’t understand what these things are doing to us at the cellular level.

    I do not agree that it is ‘sensible’ to ‘pay attention’ to such claims. By that I mean: don’t be gullible. Instead, verify. Check with a reliable (preferably disinterested) source before lending any credence to the inundation.
    The usual problem with the “X causes cancer” or “Y is poison” scare-stories is the deliberate omission of information about dose. The canola oil story is a great example.
    The fact is that many chemicals have some mutagenic effect, so sufficiently high exposures could increase your risk of cancer to some extent. It’s ALL a matter of degree. (I should mention in passing that the fact that mutagens cause cancer destroys the thesis of this OP. Heh.) For smoking, asbestos, and benzene, typical exposures significantly increase cancer risk. For Round-Up (and canola oil), not so much. You should definitely avoid sunlight and alcohol, mind you.
    😮

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  14. Dang! I was really hoping that “smoking causes cancer” was a hoax, and I could resume the habit.

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  15. Unfortunately, smoking also causes atherosclerosis. But it was fear of cancer that made me give it up…

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  16. 2014 : WHAT SCIENTIFIC IDEA IS READY FOR RETIREMENT
    “Somatic Mutation Theory of Cancer
    Cancer is one of the most intensively studied phenomena in biology, yet mortality rates from the disease are little changed in decades. Perhaps that’s because we are thinking about the problem in the wrong way.

    A major impediment to progress is the deep entrenchment of a 50 year-old paradigm, the so-called somatic mutation theory. It goes like this. A somatic cell serially accumulates genetic damage, eventually reaching a point at which it decouples from the organism’s regulatory systems and embarks on its own agenda.
    Cancer cells acquire a range of distinctive hallmarks—unfettered proliferation, evasion of apoptosis, motility and migratory powers, genomic rearrangements, epigenetic alterations, and changes in the mode of metabolism, chromatin architecture and elasticity (to mention a few)—that collectively confer remarkable robustness and survivability. In the standard picture, cancer, with all these attendant hallmarks, is considered to be re-invented de novo in each host organism: the result of a dream run of “lucky” genetic accidents. The gain of all these amazing fitness functions, co-located in the same neoplasm (population of new cells), over a period of as little as months or even weeks, is attributed to a sort of ultra-fast-paced Darwinian evolution going on in the body of the host organism. Unfortunately this theory, despite its simplicity and popular appeal, has only one successful prediction: that the administration of chemotherapeutic drugs is very likely to fail on account of the neoplasm’s ability to rapidly evolve a resistant sub-population.

    Armed with the somatic mutation paradigm, the research community has become fixated on the promise of sequencing technology, which enables genetic and epigenetic changes in cells to be measured on a vast scale. If cancer is caused by mutations, so the reasoning goes, then maybe subtle patterns can be teased out of petabytes of bewildering cancer sequencing data.

    https://www.edge.org/response-detail/25380

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  17. Temozolomide Induced Hypermutation in Glioma: Evolutionary Mechanisms and Therapeutic Opportunities
    “Glioma are the most common type of malignant brain tumor, with glioblastoma (GBM) representing the most common and most lethal type of glioma. Surgical resection followed by radiotherapy and chemotherapy using the alkylating agent Temozolomide (TMZ) remain the mainstay of treatment for glioma. While this multimodal regimen is sufficient to temporarily eliminate the bulk of the tumor mass, recurrence is inevitable and often poses major challenges for clinical management due to treatment resistance and failure to respond to targeted therapies. Improved tumor profiling capacity has enabled characterization of the genomic landscape of gliomas with the overarching goal to identify clinically relevant subtypes and inform treatment decisions. Increased tumor mutational load has been shown to correlate with higher levels of neoantigens and is indicative of the potential to induce a durable response to immunotherapy. Following treatment with TMZ, a subset of glioma has been identified to recur with increased tumor mutational load. These hypermutant recurrent glioma represent a subtype of recurrence with unique molecular vulnerabilities. In this review, we will elaborate on the current knowledge regarding the evolution of hypermutation in gliomas and the potential therapeutic opportunities that arise with TMZ-induced hypermutation in gliomas.

    https://www.frontiersin.org/articles/10.3389/fonc.2019.00041/full

    If TMZ induces hypermutations in gliomas, why would anybody who believes that mutations lead to cancer like gliomas recommend it?

    Unless of course…

    How does TMZ work other than inducing more mutations in tumors?

    “…TMZ’s most common side effects include hematological toxicity and gastrointestinal troubles, with nausea, vomiting, and anorexia being most common in patients …”

    Therapeutic fasting can have the same effect without toxicity and hypermutations by the mechanism know as anti-Warburg effect…

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439413/

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