Genetic Flaws in the gene COMT and the development of certain diseases and certain cancers

In my previous article, I wrote about how ‘variants’ or ‘flaws’ in our gene COMT (catechol-M-transferase) influence the development of disorders of chronic, unmanaged stress like insomnia, fibromyalgia, anxiety, PTSD, burn-out, and so on.

Today, I would like to dive a little deeper into the subject, and discuss some interesting features of COMT in order to shed more light on how our gene expression influences both our body / mind, and predisposes us to diseases if we don’t act in time to avoid them from developing.

As mentioned already, COMT gene plays a paramount role in determining our body’s ability to metabolize our neurotransmitters dopamine, adrenaline and noradrenaline, as well as our hormone estrogen. Some of our neurotransmitters are excitatory, and provide us with enthusiasm, mental focus, and optimism for the day ahead; while others are calming and reduce activity of the neurons, thus allowing us to relax, unwind, and feel in line with the goodness of life.

The right balance of neurotransmitters will determine whether we feel clear-headed instead of foggy; and happy and satisfied instead of anxious, pessimistic, and blue. Dopamine, adrenaline and noradrenaline are all excitatory neurotransmitters that energise the way we feel or perceive certain situations of life. In regards to estrogen, COMT helps to break down estrogen byproducts that have the potential to cause DNA mutations and thus cancer. Estrogen is an indispensable hormone to glucose homeostasis, immune robustness, bone health, cardiovascular health, fertility, and neural functions [1], but in either excess or deficiency it will give way to auto-immune disorders, tumours, cancer [1], osteoporosis, uterine fibroids, infertility, PCOS, endometriosis, depression, and cardiovascular disease.

Genetic polymorphisms or SNPs (flaws) of COMT will determine how we respond to PAIN and STRESS, and to how we metabolise ESTROGEN. This explains why some people are anxious and some others never seem to be bothered by anything much. Or why some people can’t sleep well, while others sleep like logs; or why some people get breast or prostate cancer, and others don’t, and so on.

Although our DNA is fixed and we cannot change it, the way our genes express themselves can be influenced with epigenetics in order to obtain therapeutic outcomes. It means that what really matters in the end is not the inherited gene itself, believe it or not, but all the factors “around the gene” that effect its expression, namely diet, stress management, gut microbiome, nutrient status, toxic load, and lifestyle.

Apart from influencing the metabolism of estrogen, dopamine, adrenaline and noradrenaline, COMT will also determine how we process some substances called catechols which are found in stimulating drinks and foods like tea, coffee, and chocolate; in spices and herbs like peppermint, parsley, thyme; and in certain thermogenic supplements like green tea extract (EGCG), green coffee-bean extract, or quercetin. This explains why some people get hyper when they drink coffee and some don’t; or why some supplements work to help us increase energy metabolism or not.

SNPs of COMT will determine whether its activity is slow or fast.

Let’s see how this affects us


Dopamine, adrenaline and noradrenaline will provide us with drive, determination, buoyancy, and optimism for the day. But if COMT expresses itself slowly, it will be slower in processing these chemicals of excitation. In other words, if we engage in too much excitatory activity (strenuous exercise, competitive work, dramatic relationships, etc.), there will be dopamine, adrenaline, and noradrenaline in the system for too long, preventing us from unwinding, relaxing, and even dozing off and nicely falling asleep at bed time.

When this happens, estrogen metabolism will be upregulated, leading to two undesirable phenomena: 1) conversion of estrogens into pro-carcinogenic compounds; and 2) higher levels of estrogen, and thus, estrogen dominance [2] [3]. Estrogen dominance is caused by low progesterone and high estrogen and leads to disorders like (PMS), mood swings, weight gain / obesity, fatigue, breast tenderness, depression with anxiety or agitation, brain fog, headaches, infertility, irregular menstrual periods, irritability, insomnia, PCOS, sluggish metabolism, water retention, hypothyroidism, cancer (breast, uterine, ovaries, prostate) and uterine polyps/fibroids. In men, it causes “man boobs” or gynecomastia, benign prostatic hyperplasia, and cancer of the prostate [4].


If COMT is fast, your brain chemicals of enthusiasm and determination will have a rather short life. While your temperament will be nice and calm, you won’t be strong on the motivation side and will have tendency towards opting more easily for activities requiring less effort and engagement from your side. Because your enthusiasm and determination are not generally too high, you will easily go for quick energy fixes to feel awake and present, like smoking, sugary snacks, high carb dishes, coffee, Red Bull, guarana, etc. Your high COMT activity will affect estrogen metabolism eventually influencing development of depression and cardiovascular disease. [5]

1]Estrogen exposure, metabolism, and enzyme variants in a model for breast cancer risk prediction- Cancer Inform2009;7:109–21.

2] Influence of the catechol-O-methyltransferase (COMT) codon 158 polymorphism on estrogen levels in women- Human Reproduction, Volume 18, Issue 2, February 2003, Pages 262–266,

3] Estrogeon: the necessary evil for human health, and ways to tame it – Biomedicine & Pharmacotherapy –Volume 102, June 2018, Pages 403-411

4] The Role of Estrogens in Prostate Carcinogenesis: A Rationale for Chemoprevention- Rev Urol. 2005; 7(Suppl 3): S4–S10.

5] Association of Catechol-O-methyltransferase (COMT Val158Met) with future risk of cardiovascular disease in depressed individuals – a Swedish population-based cohort study – BMC Med Genet. 2018; 19: 126.


How Do You Know If You Have A Slow Or A Fast COMT?

Check the options below and see in what group you see yourself more:


I can get headaches

I get stressed and tense quickly

Falling asleep takes for ever

My temper is short and I easily get impatient or irritable

I suffer from bad PMS; bad peri-menopausal; or bad menopausal symptoms

I feel much more physical pain than other people do


I can’t easily focus my mind on things that seem to be important to others

I love to play video-games for hours, smoke, drink alcohol, shop, and I get addicted to these easily.

It’s difficult to get me to do things that I’m not passionate about. I easily lack motivation.

I love sugar! It gives me energy! I couldn’t live without my carbs!

I sleep like a baby! That’s never been a problem!


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