Gene mutations are often discussed when talking about the cause of disease. There are many well-known gene mutations such as:

Cystic fibrosis, sickle cell anemia, Tay-Sachs disease, phenylketonuria and color-blindness, among many others.

Sometimes, gene mutations prevent one or more of certain proteins from working properly. By changing a gene’s instructions for making a protein, a mutation can cause the protein to malfunction or to be missing entirely. When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development or cause a medical condition. A condition caused by mutations in one or more genes is called a genetic disorder.

Some mutations happen during cell division, when DNA gets duplicated. Still other mutations are caused when DNA gets damaged by environmental factors, including UV radiation, chemicals, and viruses. Most mutation are passed down by our parents…..

Cancer usually results from a series of mutations within a single cell. In some cases, a faulty, damaged, or missing p53 gene is to blame. The p53 gene makes a protein that stops mutated cells from dividing. Without this protein, cells divide unchecked and become tumours.

Genetic tests are now available for a range of cancers. These tests don't test for cancer directly, but instead indicate an increased likelihood of developing a cancer. Likelihood is far from certainty, and cancer may or may not develop, since it must be triggered by additional mutations.

Meanwhile, many cancers develop in persons without so-called "cancer genes." For example, the two gene variants that have been linked with breast cancer, called BRCA1 and BRCA2. These are involved in only 5% of breast cancer cases.

SNPs (pronounced ‘snips’) which is short for single-nucleotide polymorphism are the most common genetic variation among people.  

Each SNP represents a difference in a single DNA building block, called a nucleotide. There are four nucleotide which make up all DNA; Thymine, Cytosine, Adenine and Guanine. 

For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA. This can happen only on one allele, resulting in one wild-type allele and one mutated allele and called heterozygous or on both allele and therefore called homozygous.


Most of the time these SNPs don’t have any influence how our body works.

But some SNP’s can affect us immensely and make a difference in our health and mood. One example is the MTHFR gene, which can create a myriad of problems such as birth defects, miscarriages, cancer, mood disorders and many more.
Epi- is a prefix taken from the Greek that means “upon, at, by, near, over, on top of, toward, against, among.” Epi-genetics are the factors that prompts them to express negatively or positively. This contributes to all known
Epigenetics are how we influence the genetic and cellular expressions that mani-fest as signs, symptoms and disease states by modifying factors like diet, lifestyle, and biological function (or how the body performs its many jobs).

Having genetic polymorphism on certain genes does not mean that certain diseases will be expressed. But on the other side it certainly means if a healthy lifestyle, diet etc. aren’t followed that the likely hood to develop certain disease is higher than normal.

It is validated to test for specific genes for cancer and chronic diseases. Without any doubt gene testing could be very helpful in disease prevention. If a person eats a clean healthy diet, enjoys deep and satisfying sleep, avoids toxins, and keeps stress under control, testing is generally not necessary.

This is a list of genes, which could be important to test (the list is not complete though):


MTHFR - Methylenetetrahydrofolate reductase

The connection between genetic variants – SNPs and diseases has revealed the importance of a metabolic pathway in the body that is critical to maintaining health. The methylation cycle, it turns out, is involved in many regulatory processes and genetic defects that can be particularly damaging.

The MTHFR gene initiates the Methylation cycle, a process that provides methyl to at least two hundred functions in the body.

Methylenetetrahydrofolate reductase (MTHFR) is the enzyme that catalyzes the irreversible reduction of 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate. 5-methyl tetrahydrofolate is the methyl donor for the conversion of homocysteine to methionine, precursor of SAMe.

Polymorphism on the MTHFR (677) gene shows a reduced ability to convert folic acid to the active form of folate, 5-methyltetrahydrofolate. This is associated with higher risk of many different diseases and is implicated in the pathogenesis of cancer and neurodevelopment disorders. The defective MTHFR 677 gene can lead to higher homocysteine levels. High homocysteine levels are associated with: irritation of the blood vessels, increased risk for hardening of arteries and blood clots in veins, referred to as venous thrombosis.

Associated diseases are:

Alzheimer disease, Asthma, Atherosclerosis, Autism, Bipolar Disorder, Bladder Cancer, Blood Clots, Breast Cancer, Chemical Sensitivities, Chronic Fatigue Syndrome, Epilepsy, Fibromyalgia, Gastric Cancer, Glaucoma, High Blood Pressure, IBS, Male infertility, Migraines, MS, Parkinson’s Disease, Stroke, Thyroid Cancer, Miscarriages, Preeclampsia, Spina bifida, Cleft Palate….

The above diagram of the folate/methionine cycle as well as the involved enzymes and its cofactors. If there is a polymorphism on the MTHFR gene and not enough cofactors such as L-5MTHF, Vitamin B12 and Vitamin B6 available then we have low methionine and therefore low SAMe leading to:

  • Disruption of gene expression
  • Decreased neurotransmitter function
  • Decreased myelination
  • Poor cellular energy transfer
  • Deficient fatty acid metabolism
  • Increased allergic reactions.

MTHFR as the key regulator enzyme in folate and homocysteine metabolism is also connected directly with the production of glutathione.

People with MTHFR mutations almost always have low glutathione levels, making them more susceptible to stress and oxidative stress while making them far less tolerant to toxins. This gets much worse with age, as the accumulation of toxins and cumulative damage of oxidative stress take their toll on the body.

Interventions for not proper functioning methylation:

Methylated supplements of:

  • Methylcobolamin Vit. B12
  • L5-Methyltetrahydrofolate
  • Riboflavin Vitamin B2
  • P5P Vitamin B6

If these nutrients don’t reduce elevated homocysteine, then Methylation cycle is blocked by a number of other reasons:

  • Inflammation
  • Oxidative stress
  • Heavy metal
  • Folic acid (which blocks folate receptors)
  • Yeast overgrowth
  • SIBO
  • Infection
  • Other genes which are not working enough.

There are people which can live and function perfectly with polymorphism on the MTHFR gene if they live a clean and healthy live. On the other side there can be people who don’t have a polymorphism on the MTHFR gene but still influence the proper working of the gene due to:

  • Inadequate amount of methylfolate, methylcobolamin, riboflavin
  • Exposure to industrial chemicals,
  • Psychological stress
  • Physical stress
  • Hypothyroidism
  • Folic acid


  • Genetic testing
  • Fasting Homocysteine levels
  • Methylation Panel. This test checks homocysteine, cysteine, methionine, SAMe, SAH, and SAM:SAH ratio. The result will give a clear indication of how the methylation cycle is doing. It will not give any insight of why.


Zhang, B., Zhang, W., Yan, L., & Wang, D. (2017). NU SC. Clinica Chimica Acta.

The methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is closely related to the acute lymphoblastic leukaemia (ALL) indicated by many previous epidemiologic studies. However, their conclusions were still conflicting. Methods Our aim is to evaluate their associations using a more comprehensive updated meta-analysis. Electronic searches were conducted to select published studies prior to February, 2016. Results Totally, 39 case-control studies including 6,551 ALL cases and 10,918 controls were selected in current meta-analysis. The association was detected significantly between MTHFR C677T polymorphism and ALL reducing susceptibility. Conclusions Our results indicate that the MTHFR C677T polymorphism may be a promising ALL biomarker and studies to explore the protein levels of the variants and their functional role are required for the definitive conclusions.

Zhang, Y., Jia, H., Wang, S., & Jiang, D. (2017). Cumulative review and meta-analyses on the association between MTHFR rs1801133 polymorphism and breast cancer risk: a pooled analysis of 83 studies with 74,019 participants.Minerva medica, 108 1, 57-73.

The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To clarify the precise effects of MTHFR polymorphisms on the risk of breast cancer, a systemic review and most comprehensive meta-analysis of all available studies relating MTHFR rs1801133 gene polymorphism to the risk of breast cancer was conducted.

Eligible articles were identified by search of databases including Medline (Mainly PubMed), Embase, Web of Science, Chinese Biomedical Literature database (CBM), CNKI and Wanfang Medical databases. Crude ORs with 95% CIs were used to assess the strength of association.

Finally, a total of 83 studies with 35,029 cases and 38,990 controls were included. Overall, MTHFR rs1801133 gene polymorphism was proved to contribute to the risk of breast cancer under all genetic models (TT vs. CC: Pheterogeneity <0.001, OR=1.141, 95%CI=1.065-1.222, P <0.001; TT vs. CT: Pheterogeneity <0.001, OR=1.085, 95%CI=1.021-1.154, P=0.009; TT + CT vs. CC: Pheterogeneity <0.001, OR=1.040, 95%CI=1.020-1.061, P <0.001; TT vs. CC + CT: Pheterogeneity <0.001, OR=1.131, 95%CI=1.052-1.215, P=0.0478; T allele vs. C allele: Pheterogeneity <0.001, OR=1.040, 95%CI=1.009-1.071, P=0.010).

The results of this meta-analysis suggest that MTHFR rs1801133 gene polymorphism may the therapeutic target for breast cancer.

Yi-cheng, W., Ming-tsung, W., Yan-jun, L., & Feng-yao, T. (2015). Regulation of Folate-Mediated One-Carbon Metabolism by Glycine N -Methyltransferase ( GNMT ) and Methylenetetrahydrofolate Reductase ( MTHFR ), 148–150.

Folate-mediated one-carbon metabolism is an important therapeutic target of human dis- eases. We extensively investigated how gene-nutrient interactions may modulate human cancer risk in 2 major folate metabolic genes, MTHFR and GNMT. The biochemical impacts of MTHFR and GNMT on methyl group supply, global DNA methylation, nucleotide biosynthesis, DNA damage, and parti- tioning of the folate dependent 1-carbon group were carefully studied. The distinct model systems used included: EB virus-transformed lymphoblasts expressing human MTHFR polymorphic genotypes; liver- derived GNMT-null cell-lines with and without GNMT overexpression; and HepG2 cells with stabilized inhibition of MTHFR using shRNA, GNMT wildtype, heterozygotous (GNMThet) and knockout (GNMTnul) mice. We discovered that the MTHFR TT genotype significantly reduces folate-dependent remethylation under folate restriction, but it assists purine synthesis when folate is adequate. The advantage of de novo purine synthesis found in the MTHFR TT genotype may account for the protective effect of MTHFR in human hematological malignancies. GNMT affects transmethylation kinetics and S-adenosylmethionine (adoMet) synthesis, and facilitates the conservation of methyl groups by limiting homocysteine remethyl- ation fluxes. Restoring GNMT assists methylfolate-dependent reactions and ameliorates the consequences of folate depletion. GNMT expression in vivo improves folate retention and bioavailability in the liver. Loss of GNMT impairs nucleotide biosynthesis. Over-expression of GNMT enhances nucleotide biosynthesis and improves DNA integrity by reducing uracil misincorporation in DNA both in vitro and in vivo. The systematic series of studies gives new insights into the underlying mechanisms by which MTHFR and GNMT may participate in human tumor prevention.

Yang, L., Wang, X. W., Zhu, L. P., Wang, H. L., Wang, B., Wu, T., & Zhao, Q. (2016). Relationship between genetic polymorphisms of methylenetetrahydrofolate reductase and breast cancer chemotherapy response, 70(January).

Activity of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, is influenced by mutations in the corresponding gene, contributing to a decrease in 5,10-MTHF. Due to such polymorphisms, individuals differ in MTHFR enzyme activity and plasma folate levels. We investigated the relationship between two common MTHFR polymorphisms (C677T and A1298C) and breast cancer (BC) chemotherapy response. From February 2013 to January 2016, 148 advanced BC patients at the Center Hospital of Cangzhou were enrolled and treated with six different chemotherapy regimens. Subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Forty-one (27.7%), 70 (47.3%), and 37 (25.0%) patients carried the C/C, C/T, and T/T C677T genotypes, respectively; 101 (68.2%), 42 (28.4%), and 5 (3.4%) had the A/A, A/C, and C/C genotypes of A1298C, respectively. Total chemotherapy efficacy was 66.9% (99/148), with 7 (4.7%), 92 (62.2%), 36 (24.3%), and 13 (8.8%) cases showing complete response, partial response, no change, and progressive disease, respectively. Chemotherapy regimens did not differ in effectiveness (P > 0.05). Efficacy rates associated with C677T C/C, C/T, and T/T genotypes were 58.5, 58.6, and 91.9%, respectively, with T/T carriers exhibiting significantly better responses than the C/C (P < 0.05) and C/T groups (P < 0.05). Effectiveness among A1298C A/A, A/C, and C/C carriers was 70.6, 64.3, and 0.0%, respectively, but no difference was established between these genotypes in this regard (P > 0.05). The MTHFR C677T genotype may be associated with BC chemotherapy response and could be of great value in guiding individualized treatment for this disease.


COMT- Catechol-O-methyltransferase

COMT breaks down estrogen, catecholamines and neurotransmitters including dopamine, epinephrine and norepinephrine.

Heterozygous or homozygous variants for the COMT V158M methionine allele slow down the COMT enzyme, affecting estrogen metabolism and the breakdown of stress hormones (catecholamines)

An impaired COMT leads to an increased risk of neuropsychiatric disorders, impaired estrogen metabolism (increased risk of estrogen related cancers), increased sensitivity to pain and fibromyalgia.

COMT is also important in the detoxification of xenobiotics and metabolism of catechol drugs.

Dopamine, epinephrine and norepinephrine are all stress neurotransmitters. They are designed to make us alert, focused and ready to spring into action. When the stress neurotransmitters are high we are in a panic, anxious and unable to settle. We are in overdrive, unable to focus and often unmotivated. A slow COMT and a non-efficient Methylation cycle slow down COMT even more. This means that more stress neurotransmitters and estrogen remain in the system, longer than they should.

Polymorphism on COMT gene is significantly associated with prostate cancer. See picture below and study.

Laverdi, I., Fradet, Y., Caron, P., Lacombe, L., & Guillemette, C. (2014). Steroidogenic Germline Polymorphism Predictors of Prostate Cancer Progression in the Estradiol Pathway, 2971–2984.


Levodopa (Parkinson’s disease drug) boosts dopamine production, which causes a huge strain on the COMT gene, thereby increasing dopamine quinone…which in turns makes Parkinson’s worse. Dopamine quinone is toxic to the brain.


  • Because COMT depends on the Methylation Cycle it also depends on the nutrients important for the Methylation Cycle: Riboflavin B2, Folate B9, Cobalamin B12, protein and magnesium.
  • Magnesium supplementation is necessary for COMT function while COMT activity is inhibited by high amounts of calcium/low magnesium supplementation and high iron. Magnesium can be found in dark leafy greens, nuts, seeds, avocados, fish and whole grains. Magnesium deficiency is very prevalent around the world. Common reasons are caffeine intake and long-term use of PPIs (Proton Pump Inhibitors)
  • In vitro research has found that bisphenol (BPA) plastic bottles inhibit COMT activity. Other sources include: plastic wrap, styrofoam cups, non-organic meat and dairy, non-organic plants sprayed with pesticides, unfiltered tap water, personal care and laundry products that contain parabens, artificial flavours and sweeteners and unfermented soy.
  • Homozygous COMT carrier +/+ may be more sensitive to catechols in green and black tea, wine and coffee.
  • Mercury toxicity also inhibits COMT activity through inhibition of S-adenosylmethionine (SAM), a coenzyme for COMT.
  • High homocysteine levels slow down COMT further.
  • Supplementation with high doses of Quercetin could be counteractive with homozygous COMT carrier.


NQ01- Quinone reductase

Quinone reductase is a detoxification enzyme (Phase 2) encoded by NQ01 gene. The enzyme is involved in the body’s defense against oxidative stress. It plays an important role in detoxifying numerous endogenous and environmental toxins. Its pathway is regulated by Keap 1/ NRF2/ARE.

The NQ01 gene is called the anti-cancer gene as it binds and stabilizes the tumour suppressor gene p53.

NQO1 helps with stresses such as from polyaromatic toxins and carcinogens, or by helping break down superoxides and peroxides. NQO1 directly scavenges superoxide.

NQO1 is employed in the removal of a quinone from biological systems as a detoxification reaction:  NAD(P)H + a quinone →NAD(P)+ + a hydroquinone. Many of the hydroquinone products then get bound to glucuronides and sulphates and excreted.

Laverdi, I., Fradet, Y., Caron, P., Lacombe, L., & Guillemette, C. (2014). Steroidogenic Germline Polymorphism Predictors of Prostate Cancer Progression in the Estradiol Pathway, 2971–2984.

Low levels of NQO1 has been associated with:

  • Many tumors – individuals with decreased NQO1 expression/activity have reduced p53 stability.  
  • Alzheimer Disease
  • Breast cancer. Patient who were heterozygous had a poorer outcome to adjuvant doxorubicin and cycliophospamide therapy, with or without tamoxifen.

Jamieson, D., Cresti, N., Bray, J. et al. Two minor NQO1 and NQO2 alleles predict poor response of breast cancer patients to adjuvent doxorubicin and cyclophosphamide therapy. Pharmacogenetics and Genomics. 2011. Vol 21, Issue 12, 808-819

  • There is a higher risk in Caucasians for colorectal cancer when carrying the CT heterozygous allele. 

Ding RLin SChen D., Association of NQO1 rs1800566 polymorphism and the risk of colorectal cancer: a meta-analysis. Int J Colorectal Dis.2012 Jul;27(7):885-92. Epub 2012 Jan 4.

  • Gastric Cancer: The CT allele ( heterozygous) was significantly associated with increased risk for gastric cancer.

Malik, M., Zargar, S., and Mittal, B. Role of NQO1 609C>T and NQO2-3423G>A Polymorphisms in Susceptibility to Gastric Cancer in Kashmir ValleyDNA and Cell Biology. May 2011, 30(5): 297-303.

  • Lung cancer: Having at least one C (Val) allele in CYP1B1 Leu432Val and NQO1 609C>T polymorphism was associated with the highest increase in risk of lung cancer in people who had never smoked, but had any environmental tobacco smoke exposure (OR=7.68).

Wenzlaff, A., Cote, M., Bock, C., et al. CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study. Carcinogenesis. 2005. 26 (12):2207-2212.

  • Prostate Cancer: The homozygous gene is significantly associated with increased prostate cancer risk.

Mandal, R.m Nissar, K. and Mittal, R. Genetic variants in metabolizing genes NQO1, NQO2, MTHFR and risk of prostate cancer: a study from North India. Mol Biol Rep. 2012. 39, 11145-11152



All interventions that increase Nrf2 pathways:

  • Sulforaphane

Guerrero-Beltrán CE,Calderón-Oliver MPedraza-Chaverri JChirino YI.,Protective effect of sulforaphane against oxidative stress: recent advances, Exp Toxicol Pathol.2012 Jul;64(5):503-8. Epub 2010 Dec 3.

  • Curcumin
  • Resveratrol


Phase 1 and Phase 2 Detoxification:

The body’s ability to remove waste products and toxins from our body, plays a significant role in disease development. It is essential for all cells to be able to rid themselves of toxins, whether these toxins come from the environment, such as pollution, diet, active or passive cigarette smoke, pesticides, or from our own cellular activity.

The process of detoxification involves two phases in the liver. The most important genes to look at are:

Phase 1: 

CYP1B1- Cytochrome P450 1B1

CYP1B1 is involved in the Phase I Detoxification process of eliminating numerous xenobotics and environmental toxins such as polycyclic aromatic hydrocarbons PAH (cigarette smoke, car exhaust fumes, char grilled meats i.e. well barbequed meats etc.), chlorinated benzenes (solvents).

CYP1B1, is also involved in the metabolism of estrogen. It catalysis the oxidation of estrogens to catechol estrogens and estrogen quinones. These active metabolites are capable of causing DNA damage. Therefore, CYP1B1 plays a potentially important role in tumorigenesis.

CYP1B1 is expressed in several extrahepatic tissues, including mammary tissue, uterus, kidney, prostate and lung. CYP1B1 protein appears to be overexpressed in breast tumours as well as in other tumour tissues, like lung, colon, skin, ovaries and testis.

A significant overall association between CYP1B1 polymorphisms and breast cancer has been shown among Chinese, Japanese and Turkish women. If exposures, like tobacco smoking and long-term use of HRT are taken into account, there is further evidence for increased breast cancer risk among women with the CYP1B1 432Val alleles. CYP1B1 enzymes preferentially catalyse 4OH at a rate 18-20 fold higher than other CYP450 enzymes.

Polymorphism on the CYP1B1 gene increases its activity and therefore the production of intermediate Reactive Oxygen Species ROS.  

So, if CY1B1 activity is high and COMT activity low then there is potentially a higher risk of DNA damage genotoxic carcinogenesis. See picture below.

(Pia Sillanpa 2007)

Tsuchiya, Y., Nakajima, M., & Yokoi, T. (2005). Cytochrome P450-mediated metabolism of estrogens and its regulation in human. Cancer Letters, 227(2), 115–124.

Gajjar, K., Martin-Hirsch, P. L., & Martin, F. L. (2012). CYP1B1 and hormone-induced cancer. Cancer Letters, 324(1), 13–30.

Zimarina, T. C., Kristensen, V. N., Imianitov, E. N., & Bershteĭn, L. M. (2004). [Polymorphisms of CYP1B1 and COMT in breast and endometrial cancer]. Molekuliarnaia Biologiia, 38(3), 386–393. Retrieved from

Trubicka, J., Grabowska-k, E., Suchy, J., Serrano-fernandez, P., Kurzawski, G., Cybulski, C., … Scott, R. J. (2010). Variant alleles of the CYP1B1 gene are associated with colorectal cancer susceptibility, 4–9.

Wang, F., Zou, Y., Sun, G., Su, H., & Huang, F. (2010). Association of CYP1B1 gene polymorphisms with susceptibility to endometrial cancer : a meta-analysis, 112–120.


Cyp1A1- Cytochrome P450 1A1

CYP1A1 in involved in the Phase I Detoxification process of eliminating numerous xenobotics and environmental toxins such as polycyclic aromatic hydrocarbons PAH (cigarette smoke, car exhaust fumes, char grilled meats i.e. well barbequed meats etc) as well as chlorinated benzenes (solvents). CYP1A1 is involved in the metabolism of estrogen. It catalyse the oxidation of estrogens to catechol estrogens and estrogen quinones.

Polymorphism on the CYP1A1 gene increases its activity and therefore the production of intermediate Reactive Oxygen Species ROS.  

  • Meta-analysis over 5,300 women: Val/Val allele significantly associated with ovarian cancer

Huang, M., Chen, Q., Xiao, J., Zhao, X., & Liu, C. (2012). Cytokine CYP1A1 Ile 462 Val is a risk factor for ovarian cancer development. Cytokine, 58(1), 73–78.

  • A meta-analysis suggests that polymorphism of CYP1A1 correlates with increased lung cancer susceptibility.

Huang, M., Chen, Q., Xiao, J., Zhao, X., & Liu, C. (2012). Cytokine CYP1A1 Ile 462 Val is a risk factor for ovarian cancer development. Cytokine, 58(1), 73–78.

  • The role of CYP1A1 in thyroid cancer initiation and progression has been investigated. The results suggest that CYP1A1 gene expression could be used as a marker for thyroid cancer.

Huang, M., Chen, Q., Xiao, J., Zhao, X., & Liu, C. (2012). Cytokine CYP1A1 Ile 462 Val is a risk factor for ovarian cancer development. Cytokine, 58(1), 73–78.

Interventions for both genes:

  • Sulforaphane can effectively bind CYP1B1

Mazur, P., Magdziarz, T., Bak, A., & Chilmonczyk, Z. (2010). Does molecular docking reveal alternative chemopreventive mechanism of activation of oxidoreductase by sulforaphane isothiocyanates ?, 1205–1212.

  • Evaluate side-effects of using Estrogen + Progestin HRT with this SNP.
  • Minimizing exposure to PAH’s (i.e. smoke & well done meats), dioxins (i.e. chlorine bleaching)
  • Avoiding tobacco smoke both active and passive, especially women.
  • Avoiding car exhaust fumes, industrial fumes and environmental pollution.
  • Alcohol in moderation
  • Managing stress
  • Saunas are good to flush out toxins as well as for stress management
  • Consuming a diet rich in anti-oxidants (i.e. bright colourful vegetables)
  • Eating cruciferous vegetables i.e. broccoli, cauliflower
  • Eating Allium vegetables i.e. onions & garlic
  • Keeping physically active i.e. 30 – 60 minutes per day


Phase 2:

Glutathione plays a key role in the liver in detoxification reactions and in regulating the thiol-disulfide status of the cell. Glutathione synthesis is regulated mainly by the availability of precursor cysteine and the concentration of glutathione itself which feeds back to regulate its own synthesis. Glutathione helps to eliminate intermediate Reactive Oxygen Species (ROS) produced in the Phase I detoxification process.


GCLM and GCLC - Glutamate-cysteine ligase also known as gamma- glutamylcysteine synthetase

GCLM and GCLC are first rate limiting enzymes for glutathione production.

Glutathione is an endogenous anti-oxidant which plays a major role in scavenging reactive oxygen species (ROS), protects cells from oxidative stress, repairs oxidative damage, eliminates lipid peroxidation and detoxifies xenobiotics.

Glutathione synthesis is a two-step reaction, with the first step being a rate-limiting one (i.e., this step is the bottleneck of the whole process). Within this step, two amino acids are conjugated by the enzyme glutamate-cysteine ligase (GCL). GCL is a heterodimeric enzyme containing catalytic and modifier subunits, coded by the GCLCand GCLMgenes, respectively.

A polymorphism on these genes means a reduced activity.

Functional polymorphisms in the GCLC gene, which is involved in GSH-mediated lung antioxidant protection, are importantly contributing to a reduced lung function level and accelerated lung function decline, particularly in heavy smokers.

Research suggest that GCLM polymorphism impairs the antioxidant protection in conditions like oxidative stress.

Siedlinski M,Postma DSvan Diemen CCBlokstra ASmit HABoezen HM. Lung function loss, smoking, vitamin C intake, and polymorphisms of the glutamate-cysteine ligase genes. Am J Respir Crit Care Med.2008Jul 1;178(1):13-9. Epub 2008Apr 17.



Glutathione-S-transferases are a family of Phase II detoxification enzymes that catalyse the conjugation of glutathione to a wide variety of endogenous and exogenous electrophilic compounds.

It helps eliminate intermediate Reactive Oxygen Species (ROS) produced in the Phase I detoxification process, xenobiotics, many water-soluble solvents, lipid peroxides, pesticides, tobacco smoke, industrial and environmental pollutants, heavy metals and quinone estrogens. GSTP1 converts these substances to water soluble conjugates that can be excreted. GSTP1 is highly expressed in breast tissue and is the dominant enzyme for conjugation quinone estrogens in the breast. The most abundant GSTP1 enzyme in the lung, metabolizing numerous carcinogenic compounds, including benzo(a)pyrene, a tobacco carcinogen.

GSTP1 is believed to play an important role in the protection of DNA from oxidative stress.

Aynacioglu, A. S., Nacak, M., Filiz, A., Ekinci, E., & Roots, I. (2003). Protective role of glutathione S-transferase P1 ( GSTP1 ) Val105Val genotype in patients with bronchial asthma, 1, 213–217.

A polymorphism on this gene means a reduced activity. 

  • Gastric Cancer; polymorphism was significantly associated with larger tumour size and increased tumour aggressiveness.

Xu, Z., Zhu, H., Luk, J. M., Wu, D., Gu, D., & Gong, W. (2012). Clinical Significance of SOD2 and GSTP1 Gene Polymorphisms in Chinese Patients With Gastric Cancer, 1–8.

  • It has been suggested that polymorphisms in the GSTP1 gene are associated with asthma and related phenotypes.

Aynacioglu, A. S., Nacak, M., Filiz, A., Ekinci, E., & Roots, I. (2003). Protective role of glutathione S-transferase P1 ( GSTP1 ) Val105Val genotype in patients with bronchial asthma, 1, 213–217.

GSTP1 is involved in estrogen metabolism. Quinone estrogens are able to induce mutagenic DNA lesions, so the body tries to render these quinones inactive almost instantaneously by conjugating them with glutathione. It is the GSTP1 enzyme that enables this conjugation. The level of GSTP1 controls the rate at which quinone estrogens can be neutralised. The formation of GSH-estrogen conjugates reduces the level of estrogen quinones and lowering the potential for DNA damage.

Sequential Action of Phase I and II Enzymes Cytochrome P450 1B1 and Glutathione S-Transferase P1 in Mammary Estrogen Metabolism David L. Hachey, Sheila Dawling, Nady Roodi and Fritz F. Parl Cancer Res December 1 2003 (63) (23) 8492-8499;


GSTM1- glutathione S-transferase

GSTM1 is a glutathione S-transferase (GST) which play a role in the detoxification of metabolites of environmental carcinogens including tobacco smoke. There is some evidence to suggest that people with common polymorphisms of these genes may have an increased susceptibility to a range of different cancers. This susceptibility is often associated with a combined effect of other GST genes; GSTP1 and GSTT1. Polymorphisms in these genes have also been associated with pharmacogenetics, toxicity to chemotherapy, and treatment outcome in some studies.

Polymorphism on GSTM1 is either heterozygous or null/present. 

Due to the importance of this gene and the many research in relation to cancer, we have provided you the study reference with abstract.

Peddireddy, V., Badabagni, S. P., Gundimeda, S. D., Mamidipudi, V., Penagaluru, P. R., & Mundluru, H. P. (2016). gene polymorphisms with risk of non ‑ small cell lung cancer in Andhra Pradesh region of South India. European Journal of Medical Research, 1–14.

Lung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes. Reports on assessment of xenobiotic metabolizing genes like Cytochrome P 450 1A1 (CYP1A1), Glutathione -S -transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms from India are meagre, and reports from Andhra Pradesh are lacking.
Assessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes. Results showed that CYP1A1 m1 'CC' genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 'AG' gene polymorphisms with 8.8-fold risk and GSTT1 (-/-) genotype demonstrated a twofold risk of disease susceptibility.
A combined role of genetic polymorphisms and smoking status can be attributed for the cause of lung cancer. Further, the association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; CYP1A1 m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and GSTM1 with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2'-deoxyguanosine. A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.

Peddireddy, V., Badabagni, S. P., Gundimeda, S. D., Mamidipudi, V., Penagaluru, P. R., & Mundluru, H. P. (2016). gene polymorphisms with risk of non ‑ small cell lung cancer in Andhra Pradesh region of South India. European Journal of Medical Research, 1–14.

The study investigated the possible influence of GSTM1, GSTT1, and GSTP1 gene polymorphisms as predisposing factors for premalignant gastric lesions as well as their interaction with H. pylori infection, gastrotoxic drugs, smoking, and alcohol consumption. In this study, 270 patients with a complet set of gastric biopsies and successfully genotyped were finally included. The GSTM1 gene polymorphism had significant contribution in mild/severe endoscopic lesions (p = 0.01) as well as in premalignant lesions (p = 0.01). The GSTM1 null genotype increased the risk for mucosal defects in H. pylori-negative patients (OR = 2.27, 95% CI: 1.20-4.37) and the risk for premalignant lesions in patients with no alcohol consumption (OR = 2.13, 95% CI: 1.19-3.83). The GSTT1 deleted polymorphism did not significantly increase the risk for premalignant lesions in the absence of gastrotoxic drugs (OR = 1.82, 95% CI: 0.72-4.74). The combined GSTT1T1 and GSTM1 null polymorphisms were borderline correlated with an increased risk for premalignant lesions (OR = 1.72, 95% CI: 1.00-2.97). The wild-type GSTP1 Ile/Ile genotype versus the variant genotypes Ile/Val + Val/Val was significantly associated with a decreased risk of gastric atrophy/intestinal metaplasia (OR = 0.60, 95% CI: 0.37-0.98). In conclusion, the GSTM1 and GSTT1 null genotypes increased the risk for premalignant and endoscopic gastric lesions, modulated by H. pylori, alcohol, or gastrotoxic drug consumption, while the presence of the GSTP1Val allele seemed to reduce the risk for premalignant lesions.

Marczewska, J., Drozd, J., Drozd, E., Krzyszto, J., Bubko, I., Bielak, M., … Wiktorska, K. (2016). ScienceDirect Up-regulation of glutathione-related genes , enzyme activities and transport proteins in human cervical cancer cells treated with doxorubicin, 83, 397–406.

Doxorubicin (DOX), one of the most effective anticancer drugs, acts in a variety of ways including DNA damage, enzyme inhibition and generation of reactive oxygen species. Glutathione (GSH) and glutathione-related enzymes including: glutathione peroxidase (GPX), glutathione reductase (GSR) and glutathione S-transferases (GST) may play a role in adaptive detoxification processes in response to the oxidative stress, thus contributing to drug resistance phenotype. In this study, we investigated effects of DOX treatment on expression and activity of GSH-related enzymes and multidrug resistance-associated proteins in cultured human cervical cancer cells displaying different resistance against this drug (HeLa and KB-V1). Determination of expression level of genes encoding GST isoforms and MRP proteins (GCS, GPX, GSR, GSTA1-3, GSTM1, GSTP1, ABCC1-3, MGST1-3) was performed using StellARray™ Technology. Enzymatic activities of GPX and GSR were measured using biochemical methods. Expression of MRP1 was examined by immunofluorescence microscopy. This study showed that native expression levels of GSTM1 and GSTA3 were markedly higher in KB-V1 cells (2000-fold and 200-fold) compared to HeLa cells. Resistant cells have also shown significantly elevated expression of GSTA1 and GSTA2 genes (200-fold and 50-fold) as a result of DOX treatment. In HeLa cells, exposure to DOX increased expression of all genes: GSTM1 (7-fold) and GSTA1-3 (550-fold, 150-fold and 300-fold). Exposure to DOX led to the slight increase of GCS expression as well as GPX activity in KB-V1 cells, while in HeLa cells it did not. Expression of ABCC1 (MRP1) was not increased in any of the tested cell lines. Our results indicate that expression of GSTM1 and GSTA1-3 genes is up-regulated by DOX treatment and suggest that activity of these genes may be associated with drug resistance of the tested cells. At the same time, involvement of MRP1 in DOX resistance in the given experimental conditions is unlikely.

Role of GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms in the response to chemotherapy and overall survival of advanced non-small cell lung cancer. Jia, J. Y. Sun, K. Y. Jia, X. C. Liu Genet Mol Res. 2016 Sep 23; 15(3) Published online 2016 Sep 23. doi: 10.4238/gmr.15037668

We evaluated the association between GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms and treatment outcomes of advanced non-small cell lung carcinoma. Between January 2010 and December 2012, a total of 244 patients with non-small cell lung carcinoma were recruited from Yiwu Central Hospital. The GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and the results were statistically analyzed. Conditional regression analysis, showed that individuals carrying the null GSTM1 were associated with an increased risk of response to chemotherapy when compared to the present GSTM1 (odds ratio = 1.88, 95% confidence interval (CI) = 1.01-3.47). Moreover, the GG genotype of GSTP1 IIe105Val was associated with a better response to chemotherapy compared to the AA genotype (odds ratio = 2.77, 95%CI = 1.14-6.64). The null GSTM1 genotype was associated with a lower risk of death from all causes when compared with the present GSTM1 genotype (hazard ratio = 2.16, 95%CI = 1.10-4.38). Moreover, the GG genotype of GSTP1 IIe105Val was correlated with a reduced risk of death from all causes compared with the AA genotype (hazard ratio = 2.94, 95%CI = 1.11-8.68). In conclusion, we found that the null GSTM1 and the GG genotype of GSTP1 IIe105Val were correlated with a good response to chemotherapy and improved overall survival of advanced non-small cell lung carcinoma patients.

Malik, S. S., Kazmi, Z., Fatima, I., Shabbir, R., & Masood, N. (2016). Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7 , 281 Prostate Cancer Cases and 9 , 082 Healthy Controls, 17, 2629–2635.

Genetic polymorphisms constitute one of the reasons behind the racial variation in prostate cancer occurrence. Published studies regarding genetic associations of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) null deletion polymorphisms with prostatic carcinoma have generated inconsistent results among different populations. To date, even a single meta-analysis is not available representing the association of these genes with prostate cancer in different ethnic groups. Therefore, the aim of the current study was to provide a clear picture of GSTM1 and GSTT1 null deletion and risk of prostate cancer among different ethnic groups (i.e. Asians, Europeans, Americans, Africans and Eurasians). A systematic search was performed with the help of various search engines to find out the all the recent studies (2004 to 2015) evaluating the role of GSTM1 and GSTT1 deletion in prostate cancer development. Odds ratios (ORs) with 95% confidence interval (CI) of a total of 34 studies with 7,281 cases and 9,082 controls was analyzed using STATA and MedCalc software. Overall, GSTM1 deletion (OR 3.67; CI 1.39-9.85; P= 0.001) was strongly associated with prostatic cancer. In the sub group analysis GSTM1 null deletion was also significantly associated with prostate cancer among Asians (OR 4.84; CI 1.08-21.5; P= 0.03), Eurasians (OR 17.69; CI 9.87-31.70; <0.001) and Americans (OR 0.11; CI 0.01-1.06; P= 0.05). No association was observed among Europeans (P=0.42) and Africans (P= 0.40). As a whole GSTT1 null deletion (OR 0.85; CI 0.28-2.58; P= 0.77) did not show anyt significant association with prostate cancer risk among different populations. When the data were stratified into different groups, however, Africans demonstrated a significant association of GSTT1 null deletion (OR 1.95; CI 1.57-2.39; <0.001) with prostate cancer, whereas no association was found among Asians (P= 0.90), Americans (P= 0.50), Europeans (P= 0.89) and Eurasians (P= 1.0). In conclusion, both GSTM1 and GSTT1 may contribute to prostate cancer development but GSTM1 may prove to be a stronger candidate risk factor.

Malik, S. S., Kazmi, Z., Fatima, I., Shabbir, R., & Masood, N. (2016). Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7 , 281 Prostate Cancer Cases and 9 , 082 Healthy Controls, 17, 2629–2635.

The super family of glutathione S-transferases (GSTs) is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1, and GST P1 affect the body's ability to detoxify a range of potential leukemogens encountered in the environment.
To address how differences in the human GST isoenzyme expression patterns influence cancer susceptibility, prognosis, and treatment.
PATIENTS AND METHODS: A total of 50 patients with acute myeloid leukemia (AML), as well as 50 age and sex matched apparently healthy volunteers were genotyped for GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and conventional polymerase chain reaction (PCR), respectively.
RESULTS: For GSTP1 313 A →G (GSTP1 Ile105Val) polymorphism, It was found that the wild genotype (AA) was significantly higher among control subjects (P value = 0.0277), while the frequency of heteromutant genotype (AG) and mutant G allele (AG + GG) was significantly higher among patients (P value = 0.0402, P value = 0.0277, respectively). For GSTM1 and GSTT1gene, we found statistically significantly higher frequency among patients regarding homozygous gene deletion (P value = 0.0005).
CONCLUSION: We demonstrated that GSTM1 null or GSTT1 null genotypes may be considered independent risk factors for AML with no impact on prognosis and GSTP1 * 105 genotype is a prognostic factor, adding independent information to the routine laboratory parameters and cytogenetic and molecular alterations of the tumor cells.

Antonova O, Toncheva D, Grigorov E Bladder cancer risk from the perspective of genetic polymorphisms in the carcinogen metabolizing enzymes. J BUON. 2015 Nov-Dec; 20(6):1397-406

Urinary bladder cancer is a socially significant healthcare problem. A diverse array of aromatic and heterocyclic amines, derived from the chemical and transport industry, diet, and cigarette smoke are considered carcinogens for the bladder. To exert their carcinogenic effect and to initiate the carcinogenic response, the arylamines require a metabolic activation by the host enzymes to chemically reactive compounds. The aim of this article was to review the latest and basic research developments on the role of the polymorphisms in the carcinogen metabolizing enzymes N-acetyltransferase (NAT), Glutathione S-transferases (GST), and Soluble sulfotransferases (SULT), with emphasis on the susceptibility to urinary bladder cancer. A PubMed search was conducted to identify original and review articles containing information about these polymophic variants in different populations and according to their prevalence in bladder cancer patients. We noticed that some genotypes were found to be predisposing and some protective for bladder cancer development. The NAT2 slow genotype, together with GSTM1 null genotype facilitated the development of bladder cancer in almost all ethnic groups. The 213His allele of the SULT1A1 gene which is associated with lower enzyme activity and decreased mutagen activation was reported to protect from bladder cancer in almost all studies.

Malik, S. S., Kazmi, Z., Fatima, I., Shabbir, R., & Masood, N. (2016). Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7 , 281 Prostate Cancer Cases and 9 , 082 Healthy Controls, 17, 2629–2635.

Oxidative stress might contribute to the occurrence of cancers, including the hematological ones. Various genetic polymorphisms were shown to increase the quantity of reactive oxygen species, a phenomenon that is able to induce mutations and thus promote cancers. The purpose of the study was to evaluate the association between CAT C262T, GPX1 Pro198Leu, MnSOD Ala16Val, GSTM1, GSTT1, and GSTP1 Ile105Val gene polymorphisms and acute myeloid leukemia risk, in a case-control study comprising 102 patients and 303 controls. No association was observed between AML and variant genotypes of CAT, MnSOD, GSTM1, and GSTT1 polymorphisms. Our data revealed a statistically significant difference regarding the frequencies of GPX1 Pro198Leu and GSTP1 Ile105Val variant genotypes between AML patients and controls (p < 0.001). Our results showed no association in the distribution of any of the CAT C262T, GPX1 Pro198Leu, GSTM1, GSTT1, and GSTP1 polymorphisms regarding age, gender, FAB subtype, cytogenetic risk groups, FLT3 and DNMT3 gene mutations, and overall survival. Our data suggests that the presence of variant allele and genotype of GPX1 Pro198Leu and GSTP1 Ile105Val gene polymorphisms may modulate the risk of developing AML.

Malik, S. S., Kazmi, Z., Fatima, I., Shabbir, R., & Masood, N. (2016). Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7 , 281 Prostate Cancer Cases and 9 , 082 Healthy Controls, 17, 2629–2635.

We evaluated the association of GSTM1 null/present, GSTT1 null/present, and GSTP1 IIe105Val polymorphisms with the clinical response to chemotherapy and treatment outcome of NSCLC. Between October 2009 and October 2012, a total of 282 patients with advanced NSCLC were enrolled into our study, and they were followed up until October 2014. The genotypes of GSTM1, GSTT1, and GSTP1 IIe105Val were performed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By logistic regression analysis, our study found that the Val/Val genotype of GSTP1 IIe105Val was associated with more CR+PR response to chemotherapy when compared with the IIe/IIe genotype, and the OR (95% CI) was 2.18 (1.16-4.12). By multivariate Cox proportional hazards regression analysis, we found the Val/Val genotype of GSTP1 was correlated with lower risk of death in advanced NSCLC (HR, 0.48; 95% CI, 0.25-0.93). However, no association was found between GSTT1 and GSTM1 polymorphisms and response to chemotherapy and overall survival of advanced NSCLC. Moreover, the IIe/Val + Val/Val genotypes of GSTP1 were associated with lower risk of death in never smokers, and the adjusted HR (95% CI) was 0.34 (0.12-0.93). In conclusion, we found that the GSTP1 polymorphism was correlated with better response to chemotherapy and lower risk of death in advanced NSCLC patients.

Malik, S. S., Kazmi, Z., Fatima, I., Shabbir, R., & Masood, N. (2016). Genetic Polymorphism of GSTM1 and GSTT1 and Risk of Prostatic Carcinoma - a Meta-analysis of 7 , 281 Prostate Cancer Cases and 9 , 082 Healthy Controls, 17, 2629–2635.

Antioxidant compounds such as glutathione and its enzymes have become the focus of attention of medical sciences. Glutathione, a specific tripeptide, is involved in many intercellular processes. The glutathione concentration is determined by the number of GAG repeats in gamma-glutamylcysteine synthetase. GAG polymorphisms are associated with an increased risk of schizophrenia, berylliosis, diabetes, lung cancer, and nasopharyngeal tumors. Cancer cells with high glutathione concentration are resistant to chemotherapy treatment. The oxidized form of glutathione is formed by glutathione peroxidases (GPXs). The changes in activity of GPX1, GPX2, and GPX3 isoforms may be associated with the development of cancers, for example, prostate cancer or even colon cancer. Detoxification of glutathione conjugates is possible due to activity of glutathione S-transferases (GSTs). Polymorphisms in GSTM1, GSTP1, and GSTO1 enzymes increase the risk of developing breast cancer and hepatocellular carcinoma. Gamma-glutamyl transpeptidases (GGTs) are responsible for glutathione degradation. Increased activity of GGT correlates with adverse prognosis in patients with breast cancer. Studies on genes encoding glutathione enzymes are continued in order to determine the correlation between DNA polymorphisms in cancer patients.

General Interventions for Phase 2 genes:

  • Nrf2 regulates the expression of g-glutamyl cysteine ligase catalytic (GCLC) and modulatory (GCLM) subunits, glutathione reductase (GR), so generally everything that helps to switch on Nrf2 will help upregulated these enzymes. (Sulforphane, Resveratrol, Curcumin, Ozone…
  • Vitamin D
  • Avoiding exposure to smoke active or passive
  • Sulforaphane activates Phase 2.
  • Garlic is beneficial for oxidative damage and reduced enzyme activity as well as cruciferous vegetables.
  • Precursor for Glutathione are: R-alpha lipoic acid, spirulina, milk thistle, selenium, N-Acetyl-Cysteine (NAC), undenatured Whey Protein (Undenatured whey proteins preserve the original bioactivity of cysteine guaranteeing the highest level of Glutathione promoting activity.)
  • Asparagus is a leading source of glutathione, broccoli, avocado and spinach are also known to boost glutathione levels. Raw eggs and garlic help to maintain optimal glutathione levels.
  • Glutamine can raise glutathione levels. Glutamine is abundant in plants and meats but gets easily destroyed by cooking. Good sources are fresh parsley and spinach.
  • Ensure adequate protein intake as the GCLM enzyme conjugates amino acids to produce glutathione.
  • Biotin provides sulfates for glutathione production.
  • Poor diet, chronic stress, strenuous exercise (though not a toxic substance but produces a lot of free radicals within the body), are other factors that deplete glutathione.
  • Avoid environmental toxins such as car exhaust fumes, herbicides, insect sprays, industrial solvents
  • Reduce caffeine intake
  • Curcumin has been found to increase expression of the glutathione S-transferase and protect neurons exposed to oxidant stress.


Anti-Oxidant Genes

Every minute of every day our body produces Reactive Oxygen Species (ROS), also referred to as free radicals. Research is demonstrating that free radicals cause oxidative stress and damage our DNA. Oxidative stress leads to ageing and underlies all disease processes, including cardiovascular disease, dementia and diabetes, premature ageing and plays a role in the development of cancer. Poor liver health, inflammation, diabetes, high cholesterol, obesity, environmental toxins, chemotherapy, radiation, and smoking will all increase free radical production and can lead to DNA damage.

Superoxide dismutase (SOD), along with catalase (CAT) and glutathione peroxidase (GPX1) form the front line of the body's antioxidant enzyme defence system. The primary endogenous antioxidant is SOD and is predominantly produced in the mitochondria within our cells.


MnSOD - Manganese superoxide dismutase

MnSOD is the primary mitochondrial i.e.endogenous anti-oxidant produced by our bodies as the first line of defence from the attack by Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS).

MnSOD influences redox regulation, offers cytoprotection and protects mitochondria, cell membranes, DNA and proteins from damaged caused by oxidative stress from normal metabolism.

The mitochondrial respiratory chain initially forms the superoxide anion radical, which the MnSOD reduces to H2O2, which is detoxified into water by mitochondrial glutathione peroxidase.

Polymorphism on the MnSOD gene is associated with breast cancer, cervical cancer, gastric cancer, liver damage, prostate cancer and Alzheimer’s disease.

P.Siianp. (2007). Polymorphic low penetrance genes and breast cancer. The role of genes involved in metabolism of xenobiotics, estrogens and reactive oxygen species. Department of Biological and Environmental Sciences Finland.

Tong, S., Lee, J., Song, E., Lee, K., Kim, M., Lee, J., … Kwon, Y. (2009). Gynecologic Oncology Functional polymorphism in manganese superoxide dismutase and antioxidant status : Their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer. Gynecologic Oncology,115(2), 272–276.


  • Avoiding factors that contribute to oxidative stress, avoiding over exposure to sun, avoiding smoking, excess alcohol and environmental toxins.
  • Parsley increases SOD activity
  • Cucumis melon + gliadin product
  • Foods rich in anti-oxidants, such as Vitamins A, C and E in fruits and vegetables, the more colourful the better.


GPX1 - Glutathione peroxidase

The protein encoded by this gene belongs to the glutathione peroxidase family, members of which catalyse the reduction of organic hydroperoxides and hydrogen peroxide (H2O2) by glutathione, and thereby protect cells against oxidative damage.

Through polymorphism and thereby downregulation of expression a wide spectrum of human malignancies, including thyroid cancer, hepatocellular carcinoma and chronic myeloid leukemia has been observed. GPX is a selenoprotein; it incorporates selenium into its protein structure. Therefore, how much a person produces is dependent on their selenium levels. 

The activity of GPX1 can prevent DNA damage and inhibit synthesis of inflammatory mediators such as prostagl- andins and leukotrienes.

A meta-analysis based on 14,372 cases with different tumour types and 18,081 controls from 31 published case–control studies. Individuals who carried variant CT were associated with an increased cancer risk. This polymorphism contributes to cancer susceptibility through a disturbed antioxidant balance.

Chen, J., Cao, Q., Qin, C., Shao, P., Wu, Y., Wang, M., & Zhang, Z. (2011). GPx - 1 polymorphism ( rs1050450 ) contributes to tumor susceptibility : evidence from meta-analysis, 1553–1561.

Breast cancer: While neither allele alone shows any change in breast cancer risk, an increase in the risk of breast cancer is observed in individuals who carry both the CC genotype (homozygeous) of MnSODand the TT genotype of GPX-1. The TT allele of GPX-1(homozygeous) results in less responsiveness to selenium, and the CC of MnSOD which is associated with increased urinary DNA adduct levels increases breast cancer risk. See link of study above.


  • Ensureglutathione status through precursors such as: Cysteine, glutamic acid, glycine, N-acetyl-cysteine (NAC), selenium, alpha lipoic acid (ALA), Milk thistle
  • Avoiding factors that contribute to oxidative stress, avoiding over exposure to sun, avoiding smoking, excess alcohol and environmental toxins.
  • Adequate level of selenium
  • Sulforaphane
  • Nrf2 supporter:


CAT- Catalase

Catalase is a heme enzyme that plays an important role in controlling the concentrations of hydrogen peroxide in human cells. It is part of the SOD cascade as the third endogenous anti-oxidant which reduces oxidative stress by converting hydrogen peroxide into water & molecular oxygen.

Catalase plays an important role in numerous oxidant – related diseases.

Alzheimer Disease:

Genetic and lifestyle-related risk factors for Alzheimer disease (AD) are associated with an increase in oxidative stress, suggesting that oxidative stress is involved at an early stage of the pathologic cascade. Moreover, oxidative stress is mechanistically and chronologically associated with other key features of AD, namely, metabolic, mitochondrial, metal, and cell-cycle abnormalities. Contrary to the commonly held notion that pathologic hallmarks of AD signify etiology, several lines of evidence now indicate that aggregation of amyloid-β and tau is a compensatory response to underlying oxidative stress. Therefore, removal of proteinaceous accumulations may treat the epiphenomenon rather than the disease and may actually enhance oxidative damage.

CAT polymorphism is associated with a higher risk of breast cancer for women on HRT (Hormone Replacement Therapy)

Quick, S. K., Shields, P. G., Nie, J., Platek, M. E., Mccann, S. E., Hutson, A. D., … Freudenheim, J. L. (2008). Effect Modification by Catalase Genotype Suggests a Role for Oxidative Stress in the Association of Hormone Replacement Therapy with Postmenopausal Breast Cancer Risk, 17(May), 1082–1088.


  • Avoiding factors that contribute to oxidative stress, avoiding over exposure to sun, avoiding smoking, excess alcohol and environmental toxins.
(Pia Sillanpa 2007)


Combinations of genes:

Researchers recognizing the issues with looking for single gene-disease connections are now investigating combinationsof genes in connection with a percentage increased risk for certain diseases.

For example:

Combination of SNPs in CYP1B1 / COMT / GSTP1 and CYP1B1 / COMT / MnSOD increase breast cancer risk by 2.7 and 12.2-fold respectively.

Cerne, J., Pohar-perme, M., Novakovic, S., Frkovic-grazio, S., & Stegel, V. (2011). Combined effect of CYP1B1 , COMT , GSTP1 , and MnSOD genotypes and risk of postmenopausal breast cancer, 22(2), 110–119.



We are right at the beginning of understanding how gene express and what influences certain genetic polymorphism have on our health. We also know that genes don’t act alone and that cellular function depends on the expression of many genes.

Genes even interact with other genes to influence their own expression.

Nevertheless we know what a strong influence certain pathways have on our health such as methylation, glutathionylation, catecholamine pathway, CYP450 pathways……, therefore we can’t neglect dis-functional genes and their possible impact on our health.

I am a strong believer of epigenetics and that not genes but our lifestyle dictate the development of disease. But there is no doubt that some people have a stronger genetic disposition than other people. This is exactly where we as practitioner need to be aware off and act accordingly by supporting the patient with the right nutrients and adequate lifestyle advice.

Important is:

Providing optimal and safe levels of nutrient precursors and cofactors so that DNA regulation and metabolism can function appropriately. Diet, gut support, liver support and supplementation.

Removing factors that get in the way of appropriate gene expression or that damage DNA strands or structures. Wrong diet, stress, toxins, insomnia, no exercise, deficiencies, leaky gut, inflammation……

This is a very specific and complicated chapter and was added for your information only. We decided to add this information about genetic mutations and polymorphism as it is a subject which is getting more and more popular. 

No quiz required. 

Further reading but not required:

Book: Dirty Genes by Dr.Ben Lynch