One of the beautiful things about science is that we are now looking much more deeply into the reasons why breast cancer appears to be on the rise, despite decades of more mammogram screenings, and educating women how to do monthly self breast exams.

Science is delving deeper into the reasons why breast cancer occurs and one of the most interesting (yet at the same time contentious) areas of research is genetics. Scientists are looking closely at specific genes that have been associated with breast cancer.

The genes related to breast cancer promotion (and quite a few of them have been identified) can play many different roles such as promoting inflammation, cell proliferation (rapid growth), how a person metabolizes estrogen, blocking programmed cell death, enhancing the formation of tumors – and many other functions.

Today’s article is presented at the request of several of my Facebook followers and is about two particular genes – COMT and MTHFR – both of which may possibly have an impact on rising levels of estrogen, if they are not performing as they should. Keep that word “possibly” in your mind as you read this.

Since high levels of estrogen “appear” to be one causative factor in about 80-90% of breast cancer cases and variations in these two genes are now being much more closely examined, this seems a worthy subject and of interest to the breast cancer community.

I put the word “appear” in quotation marks above because for anyone who has delved more deeply into the question of why cancer occurs, it is obvious that there are many reasons for it to appear, not the least of which are stress and inflammation. NOT necessarily an overabundance of estrogen.

But that’s part of a different discussion.

What is the COMT Gene?

The COMT gene is responsible for providing instructions to the body for making an enzyme called catechol-O-methyltransferase, also called COMT.

The COMT gene and enzyme are both super important to our health as they help to break down neurotransmitters such as dopamine, epinephrine (aka adrenaline) and norepinephrine, and hormones such as cortisol and estrogen – and anything that has the same catechol structure, including certain drugs.

The COMT gene is also essential for methylation. This is a biochemical process where atoms are transferred from one substance to another. A methyl group is one carbon atom and 3 hydrogen atoms, CH3. Simply stated, methylation involves the addition or removal of a methyl group (CH3) between substances, a vital process which happens millions of times per day in healthy cells.

What is Slow COMT?

If you have been told that you have slow COMT, you may have difficulty ridding yourself of certain neurotransmitters and hormones, which allows them to build up in the system to higher than normal levels. Experts will tell you that somewhere between 20-30% of Caucasians with European ancestry do have a COMT gene variation or polymorphism. I don’t like calling it a mutation because I think that puts a rather negative spin on things that doesn’t need to be there.

Needless to say, this description is VERY simplified because there are several different COMT variations and it can be an extremely confusing discussion. If you want all the nitty gritty details just Google “COMT variations”.

I don’t think anyone really wants me to spend a lot of time on all the gene variants, so we are going to keep this simple and just talk about slow COMT (also called the MET allele). Because of the effects that slow COMT has on estrogen and cortisol, it can directly affect breast health, stress levels and well-being. Or can it? Read on.

The recommended course of action with regard to slow COMT from naturopaths and functional medicine doctors is to get an adequate intake of B vitamins, especially B2, B6, B9, and B12. Also to get magnesium, SAMe (S-adenosyl-L-methionine), a naturally occurring substance in the body but also available in supplement form. SAMe is useful for the transfer of methyl groups (described above) and is thought to counteract a slow COMT by working as a methyl donor for COMT. Also recommended is DIM (di-indolyl-methane), a supplement made from cruciferous veggies.

People are also told to focus on foods that help to remove excess estrogen from the body such as broccoli, cabbage, Brussel sprouts, cauliflower, flaxseed, raw garlic, onions, leeks, beets, eggs, avocado – things that support Phase 2 liver detox pathways.

Those with slow COMT are also told to avoid foods or substances that increase catechols, such as the amino acids tyrosine, tryptophan, and phenylalanine (ie high-protein foods), caffeine and alcohol, smoking cigarettes.

One suggestion that I agree with is the avoidance of environmental estrogens known as xenoestrogens. For a list of the major ones, see my article Unraveling the Mystery of Xenoestrogens and Estrogen Dominance.  See also my article: Protect Yourself from Xenoestrogens & Estrogen Dominance. When we are exposed to these xenoestrogens, it creates a greater load on detoxification pathways and messes up our hormones.

You may also be told to avoid strenuous exercise, the thinking being that strenuous exercise involves methylation and increases catechols. So more gentle exercise may be good, rather than running a marathon.

Another suggestion I agree with is the avoidance of stress. As mentioned, a slow COMT can significantly limit the body’s ability to excrete stress hormones. That means during stressful times, you can feel like it affects you worse than others, seems to last longer, and can potentially do more damage. Things like meditation, mindfulness, prayer and being in nature are a good way to minimize stress.

The most contentious advice I’ve found is that people with slow COMT are told to limit catechol-containing flavonoids including quercetin, rutin, luteolin, EGCG, catechins, epicatechins, fisetin, ferulic acid, and hydroxytyrosol. These phytochemicals are found abundantly in many fruits and vegetables, green tea and herbs and are the very things we are TOLD to have as part of an anti-cancer diet and that is backed up by loads of research. Look, I understand why the advice is offered, I just personally think it’s bad advice.

I think you can drive yourself crazy with all of this, which stresses you out, and that is far worse for you than having a cup of green tea and enjoying it.

Please read on, especially the section about epigenetics for the reason why I feel this way.

What is the MTHFR Gene?

MTHFR is short for methylene tetrahydrofolate reductase and it is a gene that codes for an enzyme with the same name. We have two copies of the MTHFR gene, one from each parent. MTHFR is just possibly THE most studied gene.

It has a number of responsibilities but chiefly it helps the body convert folate (vitamin B9) into its active form so that the body can utilize it.

That may not sound like a big deal but almost every cell in the body needs active folate to properly function. Active folate is essential for methylation (discussed above), healthy cell division, DNA synthesis and repair, heart health, good vision, brain development, memory and mood, and so much more.

Folate is also required to help break down and convert homocysteine into methionine (both are amino acids). Methionine is super important for creating SAMe (mentioned above in the COMT section). MTHFR working properly means you have normal levels of homocysteine in the blood.

Slow MTHFR means that there is a gene variant which can slow down the production of the MTHFR enzyme – in some cases up to 70% slower. This can result in things like reproductive problems including miscarriages, infertility, and stillbirths. Other conditions include headaches and/or migraines, childhood behavioral disorders, chemical sensitivities, allergies, gut health problems, detox issues, sleep problems, hormonal conditions and cardiovascular diseases.

Slow MTHFR and Estrogen Build-Up

For the purposes of this article, we are mainly concerned with how slow MTHFR affects estrogen levels. Or doesn’t. I know, it’s confusing.

I have looked deeply into the studies and general consensus between experts on the matter, which has revealed the following:

– Hilariously, genetics experts call MTHFR the “motherfucker gene” (Yes they really do – see it in the acronym? Sorry if anyone is offended). Keep reading.

– Genetics experts do NOT recommend MTHFR testing for estrogen issues. See the study at [1].

– According to Dr Jen Gunter, OB/GYN and a strong critic of MTHFR testing, “there is no proof that these MTHFR variants result in any issues with excessive estrogen or a buildup of toxic estradiol-3,4 quinone. Having one of these MTHFR variants is a variation, not a problem.” In her blog on Substack, Dr Gunter has publicly stated “The American College of Medical Genetics and Genomics have been recommending against testing for MTHFR variants since 2013.” [2]

– Naturopaths and functional medicine doctors do feel there is an issue for those with MTHFR variants and suggest avoiding generic multivitamins in favor of activated B vitamins; some recommend taking glutathione or N-Acetyl-Cysteine (NAC); to get hormone levels checked; to avoid xenoestrogens; to reduce dietary triggers like gluten and oxalates; among other nutritional advice.

– The research I read – eight different studies – revealed mixed results. One 2006 case study indicated that those with MTHFR variants C677T and A1298C were actually associated with breast cancer survival [3]. Of the remaining seven studies, one study [4] found that the MTHFR C677T and A1298C polymorphisms did not alter the risk of breast cancer, but appeared to be associated with the clinical severity of breast cancer. Three of the studies [5]-[7] indicated that MTHFR variants appeared to be a breast cancer risk, two studies [8]-[9] said they did NOT appear to be a breast cancer risk. The last study and the latest one I read, published in 2021 [10], looking at postmenopausal breast cancer risk said only that “estrogen metabolic pathway polymorphisms constitute a factor to be considered simultaneously with models for breast cancer risk assessment.”

As you can see, it is a complex discussion, and you can drive yourself crazy with the tiny details of it all.

My Thoughts on the Matter

I think that genetic testing results can be a distraction from what’s really causing your symptoms. I also think that genetic testing can also be very disempowering for patients.

95% of the breast cancer patients/survivors I work with all feel that high stress levels were the cause of their breast cancer. Stress is that big of a deal, yes. Stress and poor nutrition (and a few other factors) can alter the way our genes are expressed.

If you want to really expand your mind on the subject of genetics, go and read Dr Bruce Lipton’s book “The Biology of Belief” [11]. I highly recommend doing this, the book is all about the power of epigenetics, which literally means “above genetics”.

The old way of thinking is that a person’s genes and DNA controls protein expression in the body – and therefore the risk of disease – and some scientists still do believe that. However this theory was effectively debunked in 2000 when the entire human genome was catalogued and found to contain approximately 20,000 genetic instructions, which is not nearly enough to account for the 100,000 proteins within the human body.

We are now aware that epigenetic factors are much more responsible for determining disease risk. These factors are influenced by a person’s nutrition, emotional health, lifestyle factors, environmental factors and even thoughts. Epigenetics is about turning genes on or off, of gene regulation, by utilizing these factors.

We have so much more power over genetic expression than we think we do!

In his book, Dr Lipton states that 95% of breast cancer is not due to inherited genes, but to malignancies derived from environmentally induced “epigenetic alterations”.

Not only that but we now know that up to 50% of breast cancer cases are thought to be preventable utilizing some simple changes in lifestyle and diet – things I teach on my website and in my courses.

I teach my clients not to focus on genes but rather to focus on the things they can do to powerfully take charge of their health. I have free newsletters full of tips on how to begin making those changes (you can sign up here), website articles (link) and a course called Toxic Free Me, all of which teach you what amazing things you can do to influence your health in the most positive way possible. Reach out if you need some assistance with all of this.

References:

[1] ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing – https://www.nature.com/articles/gim2012165
[2] Dr Jen Gunter on Substack: https://vajenda.substack.com/p/mthfr-testing-and-estrogen
[3] Association of MTHFR gene polymorphisms with breast cancer survival – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1634868/
[4] Can MTHFR C677T and A1298C Polymorphisms Alter the Risk and Severity of Sporadic Breast Cancer in Brazilian Women? – https://pubmed.ncbi.nlm.nih.gov/28330681/
[5] Breast cancer risk associated with multigenotypic polymorphisms in folate-metabolizing genes: a nested case-control study in Taiwan – https://pubmed.ncbi.nlm.nih.gov/17595805/
[6] Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case-control study and a pooled meta-analysis – https://pubmed.ncbi.nlm.nih.gov/17260091/
[7] Polymorphisms in the MTHFR gene are associated with recurrence risk in lymph node-positive breast cancer patients – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5024764/
[8] DNA promoter methylation in breast tumors: No association with genetic polymorphisms in MTHFR and MTR – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837294/
[9] HFE, MTHFR, and FGFR4 genes polymorphisms and breast cancer in Brazilian women – https://pubmed.ncbi.nlm.nih.gov/21625954/
[10] Influence of Estrogenic Metabolic Pathway Genes Polymorphisms on Postmenopausal Breast Cancer Risk – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910923/

[11] Lipton, B. (2005). The Biology of Belief: Unleashing the Power of Consciousness, Matter and Miracles, Santa Rosa, CA: Mountain of Love/Elite Books