MTHFR and ‘XYZ’ Cancer: Is it Related?

Do you wonder if MTHFR is related to a specific cancer?

Many do.

In order to determine if MTHFR and a specific cancer is related, one may search the medical research database, Pubmed.

Here are some results from searching the Pubmed Database on various keywords:

  • MTHFR Cancer = provides over 2,300 articles as of March 12, 2012
  • MTHFR oncology = provides same result
  • MTHFR carcinoma = provides same result
  • “MTHFR Cancer” = provides 0 results because “MTHFR Cancer” is not a specific cancer.

Evaluating the research done MTHFR may not be the best option for a few reasons:

  1. There are not enough studies done on various types of cancer and MTHFR defects
  2. Research is conflicting. One study says, “Yes, MTHFR is a risk factor” and another says, “No relation.”
  3. Time consuming. Digging through 1000’s of studies trying to find the specific cancer and MTHFR may not exist.

Other option is to understand what affect the MTHFR defects have on human function:

MTHFR Defects Lead to HYPOMETHYLATION if untreated

Hypomethylation = decreased methylation

There are many cancers that relate to hypomethylation. The research on hypomethylation is plentiful.

When determining if ‘MTHFR and ‘XYZ’ cancer are linked, using both searching methods is recommended.


“Is there a link between Chondrosarcoma and MTHFR?”

Here is an example of how to search PubMed to see if MTHFR is related to a specific cancer:

  • Chondrosarcoma MTHFR = 1 result which demonstrates no link in Turkish individuals. Small study of n=56. Not significant enough.
  • Chondrosarcoma Hypomethylation = 1 result which used a drug to induce hypomethylation in rats. Results demonstrate a link between hypomethylation and chondrosarcoma.
  • Chondrosarcoma Undermethylation = no results
  • Chondrosarcoma Hypermethylation = 3 articles which vary in their target genes. Methylation, either hyper or hypomethylation, are linked in cancer and it depends on which gene is affected.
Bottom Line:

MTHFR is linked to numerous cancers if methylation is not restored and balanced. Excessive methylation is as harmful as undermethylation. Health requires balance. Balance Methylation.

You are now immediately asking:

How to balance methylation?

Through an understanding of various markers on testing. Currently, this is being evaluated. There are a few laboratories measuring levels of methylation; however, the results are not providing useful information.

Out of all methylation tests I have evaluated, each individual has ‘normal’ methylation. I find this impossible especially since these individuals have MTHFR defects.

Rudimentary Methods to Understand if You’re Hypomethylated or Hypermethylated

  1. Measure blood levels of Histamine. Histamine requires methylation to be processed and broken down. If histamine levels are elevated, you are likely a hypomethylator. If histamine levels are normal, you are a ‘normal’ methylator. If histamine levels are too low, you are a hypermethylator.
  2. Take some Niacin in the form of nicotinic acid. Chew 1/10th a tablet of Niacin and then swallow. Niacin utilizes s-adenosylmethionine (SAM) when breaking down. If you flush strongly on 50 mg, you are likely hypomethylated (lack of SAM). If you do not flush much, you are likely a ‘normal methylator’ (balanced SAM). If you do not flush at all, you may be hypermethylated (excessive SAM).
  3. Side Effects from Methylfolate: If you are taking methylfolate and experiencing these side effects, then you are likely hypermethylated.

Comments? Share your Story. 

11 Responses to “MTHFR and ‘XYZ’ Cancer: Is it Related?”

  1. Diane April 20, 2012 at 4:15 am # Reply

    Hi Dr. Ben,

    Re being a hypomethylator:
    1. Does the lack of SAM mean you need to take TMG?
    2. I’ve read that TMG is dangerous if you have high cholesterol – is this true?

    Thank You,

  2. Cal Crilly April 23, 2012 at 8:22 am # Reply

    Well you may be the only person on the net mentioning the MTHFR1 problem and cancer.
    MTHFR1 leads to folate loss and hypomethylation of the genome as you say.
    When our genes hypomethylate our retroviruses express and this is seen in tumours and recognised as a cause of metastasis.
    The nutrients to create proper methylation being Folate, B12, B6, Selenium and Choline.
    This is balanced by Retinoic acid or vitamin A which is the natural substance to create hypomethylation of DNA along with things like Estrogen which also hypomethylate and encourage new cell growth.
    Both Vitamin A and estrogen can make retroviruses express as happens in tumour formation and fetal growth.
    Folate, B12, B6, Selenium and Choline methylate and make the retroviruses stay in the genome so you don’t want too much of say selenium as it stops growth.
    Folate methylates but is also used for cell growth.
    In the case of cancer suppressing the retroviruses stops tumour spread but once a tumour has started growing things like folate can feed a tumour.
    I’m friends with an old gentleman with the MTHFR1 problem.
    He says that tumours in people missing the MTHFR1 gene will occur more often but they will be smaller tumours due to the lack of folate to encourage their growth once started.
    It is vital someone with cancer checks to see if they have the MTHFR1 problem because they can’t cope with detoxifying chemo and so have best chance with surgery only.

    Best reference.
    “Cancer-associated DNA hypomethylation is as prevalent as cancer-linked hypermethylation, but these two types of epigenetic abnormalities usually seem to affect different DNA sequences. Much more of the genome is generally subject to undermethylation rather than overmethylation. Genomic hypermethylation in cancer has been observed most often in CpG islands in gene regions. In contrast, very frequent hypomethylation is seen in both highly and moderately repeated DNA sequences in cancer, including heterochromatic DNA repeats, dispersed retrotransposons, and endogenous retroviral elements.”
    DNA methylation in cancer: too much, but also too little

    • Dr Ben April 23, 2012 at 4:54 pm # Reply

      Cal – excellent information – thank you for sharing with others.

      Look up ‘unmetabolized folic acid’ in Medline ( and you will see that it shuts down our Natural Killer cells (NK cells) which are heavily needed to fight against cancer. So those with MTHFR who are supplementing with high dose folic acid (prescribed by doctors all the time incorrectly for MTHFR), eating enriched foods containing folic acid or taking supplements with folic acid are reducing their NK cell level. This partially explains why folic acid in high amounts can cause cancer -it is because of the high levels of unmetabolized folic acid (UMFA).

      • Cal Crilly April 24, 2012 at 12:48 am # Reply

        yes totally true, I just looked then for studies on methylated folate but they are few so it seems they are just realising this.

        “Approximately 40% of older adults in the United States have Unmetabolized serum folic acid (UMFA) that persists after a fast, and the presence of UMFA is not easily explained in NHANES by folic acid intakes alone. Given the possibility that excessive folic acid exposure may relate to cancer risk, monitoring of UMFA may be warranted.”
        Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged ≥60 y in the United States 2010

        Synthetic folic acid became trendy to stop neural tube defects in pregnancy and it does work very well there.
        The other problem is folic acid apparently chews up B12 in processing it to the usable methylated folate so you are in effect using methylation nutrients to process a methylation nutrient like folic acid into folate.
        I mention this to cancer patients (friends if unfortunate enough to happen) and say don’t take folic acid in any form as it may increase tumour growth.
        It’s simply best to eat enough greens and vegetables to get the required amount.
        People missing MTHFR1 need the methylated folate and it can be taken at much lower doses.
        I think even if a person is missing MTHFR1 and has cancer it may be prudent to simply eat well. Selenium foods and choline foods will help with cancer.
        A B12 supplement I think is safe and necessary.

        I always tell people to try Bromelain for cancer if not on blood thinners.
        It is the only safe substance apart from cimetidine that blocks CD44 or E-selectin on tumour cells to stop tumours spreading.
        Also Bromelain helps Natural Killer cells to work.

        “These results indicate a potential role for bromelain in the activation of inflammatory responses in situations where they may be deficient, such as may occur in immunocompromised individuals.”
        Bromelain activates murine macrophages and natural killer cells in vitro.

  3. Kimberly April 28, 2012 at 12:30 am # Reply

    So, interesting! While not MTHFR, it’s related-
    I was reading a study on the relation of estrogen and COMT. Dr.Ben, you mentioned COMT was a estrogen metabolizer which caught my attention, because I have severe hormone issues and believe I’m COMT+. I’m also C667T++. Two of my grandparents died of Cancer. I had lesions on my cervics removed at 24. Interestingly, this study talks about the relation Estrogen has on COMT.They studied the effects of administered Estradiol, which down-regulated COMT and Tamoxifen which up-regulated it.The COMT enzymes effected were in the PFC and Kidneys…where Dopamine is metabolized.
    So I could be not understanding this at all, but wouldn’t that suggest a vicious loop?
    COMT++ causes excess Estrogens and those unmetabolized Estrogens cause
    the COMT to further downgrade?
    If this were true, could we work on lowering environmental exposures, proper diet and detox to lower Estrogens in turn up-regulating COMT?
    It did mention that the COMT is not easily induced or suppressed and I don’t recall the doses given, but is COMT related to Cancer as well. ya think?
    BTW-I was surprised to see that 1 of the 2 COMT enzymes that break down Dopamine are in the Kidneys. I’ve have chronic Kidney problems, Estrogen dominace and a faulty COMT….related or am I stretching it? I told my My accupuncturist I had elevated excitos and he said, “fear is located in the Kidneys”. lol.

    • Kimberly April 28, 2012 at 12:32 am # Reply

      Link to the study for anyone interested.

    • Dr Ben April 28, 2012 at 8:18 pm # Reply

      Kimberly –

      Great comment – thanks for posting.

      You are right that it is a vicious loop. This is how it can get extremely complicated quickly especially when dealing with multiple mutations, the GMO foods, inappropriate medical treatment, overuse of medications, high stress and fast paced lifestyles, sedentary lifestyles and prevalence of chemicals in our environment – along with many poorly made supplements containing a bunch of garbage rather than active nutrients – in pure delivery form.

      Takes work! But – the good news – it is still possible but takes extra effort on everyone’s part and also takes effort to change business in the world – such as Monsanto, Dow Chemical and others.

    • Carol W. September 2, 2013 at 7:25 pm # Reply

      @Kimberly, Looks like a stretch to me. There’s more to estrogen-related genetics than just COMT. For example, but not limited to, there’s aromatase for estrogen synthesis, there are also CYP3A4 and phase 2 liver detox genetics (UGTs) that contribute to estrogen clearance.

      In my own case, aromatase is homozygous variant on key SNPs, so I don’t make much estrogen, COMT is homozygous variant so this helps keep what little estrogen I make in the system a longer, but wildtype on CYP3A4 and homozygous variant on key UGTs
      (gain-of- function mutations) so I clear estrogen fast otherwise. When I hit perimeno at 48, I felt like I was running on fumes, felt like I was falling thru the floor, did not have typical hot flashes but just turned red for hours on end, but a little HRT fixed me up in 1-2 days. Even small amounts of estrogen go a long way with me and make a major positive difference. That’s just an example of how key SNPs on various estrogen-related genes can work together – not just on paper or in theory, but also in practice and experience.

      Estrogen dominance is a misleading term, because it can misdirect attention toward estrogen when the problem is often low progesterone (which begins declining due to normal aging starting in a woman’s early 30s) – so estrogen becomes *relatively* high only in relation to *low progesterone*. Some women may have high *absolute* estrogen, where tested estrogen levels are high out of range. And some have both. But all that needs to be qualified and sorted before use of the ambiguous term “estrogen dominance” becomes meaningful.

      • Dr Lynch September 3, 2013 at 4:45 am # Reply

        Excellent points, Carol. Thanks for sharing.


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