Exposure to many different man-made chemical compounds occurs every day, and our exposure to new toxicants well exceeds what our ancestors experienced. Your body has fascinating ways of breaking down and eliminating toxicants, medications, and even hormones made in the body.
Detoxification often is a two-phase process. The first step (phase I) makes the molecules more reactive and phase II (conjugation) makes the molecules ready to be bound to something. This process is then followed by elimination (urine, feces).
GSTs: phase II detoxification enzymes
The glutathione S-transferase genes code for enzymes involved in the removal of a variety of carcinogens and environmental toxins.[ref]
These phase II detoxification enzymes combine the metabolites from phase I with molecules that make them less toxic and more easily excreted.
There are eight different enzymes in the GST family of genes and identified by Greek letters: alpha, kappa, mu, omega, pi, sigma, theta, and zeta. As such, abbreviations for the classes start with their first letter (i.e. GSTMA for alpha).
The GST enzymes are found in the liver, intestines, and several other tissues. They are responsible for detoxifying a large number of pesticides, herbicides, carcinogens, and chemotherapy drugs.
Glutathione, an endogenous antioxidant
The GST enzymes conjugate (bind) an antioxidant called glutathione to the substance for elimination. Glutathione is considered the master antioxidant for the body.
Once a toxic substance has been conjugated with glutathione via the GST-specific enzyme, the body excretes it via bile or urine.
One very important role performed by the GST enzymes is to rid the body of polycyclic aromatic hydrocarbons (PAHs). Cigarette smoke, diesel exhaust, and grilled meats all contain PAHs. Not to mention, PAHs are known carcinogens.[ref]
Several fairly common genetic variants can decrease the function of the GST enzymes, but with several different GST enzymes available, often the body has a backup route for getting rid of toxicants.
Importantly, environmental factors, such as exposure to toxicants (pollution, cigarette smoke) also play a large role here. It really is a matter of genetic susceptibility along with exposure to toxins and carcinogens.
Genetic variants in the GST genes:
Genetic variants greatly impact the way that your GST genes function, with common variants causing non-functioning genes.
The GSTM1 (glutathione S-transferase mu 1) enzyme helps the body detoxify several types of carcinogens, drugs, toxins, and oxidative stress byproducts.
Not everyone has a functioning copy of this gene, and the non-functioning (null) genotype shows links to cancer susceptibility.[ref] The deletion is fairly common with 50 – 78% of people, depending on ethnic group, having the null genotype for GSTM1.
Check your genetic data for rs366631 (23andMe v4 only):
- A/A: deletion (null) GSTM1 gene. 2x increased risk of breast cancer[ref], increased susceptibility to lung cancer in smokers[ref], increased risk of prostate cancer in Caucasians[ref] (common genotype in many population groups)
- A/G: GSTM1 present
- G/G: GSTM1 present
Members: Your genotype for rs366631 is —.
A non-functioning version of the GSTA1 gene is referred to in studies as GSTA1*B. A couple of studies show that with GSTA1*B there is a higher risk for colon cancer with high cruciferous vegetable intake, especially broccoli.[ref][ref] On the other hand, people with the GSTA1*B genotype and high cruciferous veggie consumption were found to have more protection against breast cancer.[ref] GSTA1*B is also associated with a higher risk of asthma and allergies.[ref]
Check your genetic data for rs3957357 (23andMe v4, v5; AncestryDNA):
- A/A: GSTA1*B, low/ non-functioning enzyme; increased risk of asthma, allergies[ref] interaction with cruciferous vegetables and cancer risk[ref][ref][ref]
- A/G: GSTA1*A/*B, somewhat lower enzyme function.
- G/G: GSTA1*A
Members: Your genotype for rs3957357 is —.
GSTP1 is involved in estrogen metabolism, and women with GSTP1 G/G were found to have a higher risk of breast cancer in a 2008 Chinese study. This increased risk was dependent, though, on the amount of cruciferous vegetables consumed. Those with the G/G alleles and the lowest intake of cruciferous vegetables seemed to have the highest risk of breast cancer.[ref]
A 2012 study on men taking Vitamin E (alpha-tocopherol) supplements found that those with GSTP1 A/A and A/G had higher levels of inflammation (measured IL-6), while those with G/G had decreased IL-6 levels.[ref]
Check your genetic data for rs1695 (23andMe v4, v5; AncestryDNA):
- A/A: typical; possibly higher IL-6 in men who take vitamin E[ref]
- A/G: typical risk of breast cancer
- G/G: reduced function, increased risk of breast cancer[ref][ref] increased risk of prostate cancer[ref] increased risk of nasal polyps[ref]
Members: Your genotype for rs1695 is —.
The GSTO1 gene codes for a glutathione-S-transferase that acts a little bit differently than the rest. This enzyme reportedly plays a pro-inflammatory role in certain situations, such as bacterial infections.[ref] Additionally, it plays a role in neutralizing oxidative stress.[ref]
Check your genetic data for rs4925 (23andMe v5; AncestryDNA):
- C/C: typical (most common);
- A/C: lower mortality in renal cell carcinoma (males); increased susceptibility to PCOS; increased skin lesions in arsenic poisoning[ref]
- A/A: lower mortality in renal cell carcinoma (males)[ref]; increased risk of PCOS[ref]; increased problems detoxifying arsenic
Members: Your genotype for rs4925 is —.
There are several dietary ways to naturally increase the amount of the GST enzymes the body produces.
The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.
Related Articles and Genes:
Estrogen – from how much is made to how it is broken down – is dependent on both genetics and lifestyle factors and affects both men and women. This article explains how estrogen is made, how it is eliminated from the body, which genes are involved, and how this influences the risk of breast cancer, prostate cancer, and fibroids.
How your genes influence BPA detoxification:
BPA, a chemical found in some plastics, has links to a variety of effects on people including obesity, insulin resistance, and epigenetic effects on the fetus. Genetics plays a role in how quickly you can eliminate BPA from your body.
Nrf2 Pathway: Increasing the body’s ability to get rid of toxins
The Nrf2 (Nuclear factor erythroid 2–related factor) signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes. This is a fundamental pathway that is important in how well your body functions. Your genetic variants impact how well this pathway functions.
Phase I and Phase II detoxification
Learn how the different genetic variants in phase I and phase II detoxification genes impact the way that you react to medications and break down different toxins.
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.