I copied this from the detoxigenomic profile but unfortunately i don't find it very helpful because i can't interpret it very well. It shows some genes carry the mutation but what does that mean to the expression? Are they downregulated or upregulated? Especially the homozygous mutation on the SOD2 gene is what concerns me.
CYP2C9
Health Implications : Cytochrome P450 2C9 is involved in the metabolism of many drugs including blood thinners like
Coumadin®. Polymorphisms may prevent the normal metabolism of these drugs and side effects are possible.
Minimizing Risks: Your health care provider has a list of drugs cleared through CYP2C9. Consult your physician. You
may still need these drugs, but your physician may opt to prescribe a smaller therapeutic dose. Should you need to be
placed on a blood thinning agent in the future, make sure your physician knows you have a genetic polymorphism that
impairs your ability to break down Coumadin®. If you are taking aspirin to reduce the risk of colon cancer, switch to a
non-aspirin alternative.
CYP2E1
Health Implications: Cytochrome P450 2E1 is involved in the activation of nitrates and nitrites (found in smoked meats
and bacon) into nitrosamines that may promote the development of colorectal cancers, especially if in combination
with a polymorphism either in CYP1A1 or GSTM1.
Minimizing Risk : Reduce or eliminate the consumption of smoked meats and bacon. Avoid exposure to industrial
solvents. Broccoli and black tea have both been shown to be significantly protective in vivo, and other cruciferous
vegetables, garlic and green tea have been shown to be protective in vitro.
Physician Recommendations:
+ - NAT2 I114T
+ - NAT2 R197Q
Health Implications: N-acetyltransferase 1 is found in extra-hepatic tissues, while NAT2 is found predominantly in the
liver and the gut. Both are used in the Phase II acetylation of numerous environmental toxins, including heterocyclic
aromatic amines. Slow acetylators do not clear toxins well and the resulting increased total toxic burden can increase
the risk of lung, colon, breast, bladder, and head and neck cancers, though results have not been consistent in all
studies. Urinary bladder cancer appears to have the most consistent association with slow acetylation.
Minimizing Risk: If you smoke, stop. Your risk of lung cancer is substantially higher than someone with normal NAT
activity. Even occasional smoking or exposure to second hand smoke is harmful. Liberal consumption of most
vegetables and fruits but especially cruciferous vegetables (broccoli, Brussels sprouts, cauliflower, watercress, and
cabbage), garlic, onions, soy, grapes and berries will increase Phase II efficiency, including acetylation.
+ - NAT2 K268R
Health Implications: N-acetyltransferase 1 is found in extra-hepatic tissues, while N-acetyltransferase 2 is found
predominantly in the liver and the gut. NAT2 is the enzyme that controls Phase II acetylation of numerous
environmental toxins, including heterocyclic aromatic amines. Rapid acetylators increase O-acetylation of toxins that
can actually make the toxins more reactive. These transformed toxins may increase risk of developing lung, colon,
breast, bladder, head and neck cancer, though results have not been consistent in all studies. Colon cancer appears to
have the most consistently reproducible association with fast acetylation.
Minimizing Risk: If you smoke, stop. Your risk of lung and breast cancer is substantially higher than someone with
normal NAT activity. Do not eat fried foods and minimize red meat as these substantially increase your risk of colorectal
cancer. Avoid well-done meats as these may substantially increase your risk of breast cancer. Liberal consumption of
most vegetables and fruits but especially cruciferous vegetables (broccoli, Brussels sprouts, cauliflower, watercress and
cabbage), garlic, onions, soy, grapes and berries will increase Phase II efficiency, including acetylation.
PRESENT GSTM1 1p13.3
+- GSTP1 A114V
+ - GSTP1 I105V
Health Implications: Glutathione S-transferases (GST) are responsible for detoxifying certain products of oxidative
stress and a variety of electrophilic xenobiotics and carcinogens such as solvents, herbicides, pesticides, polycyclic
aromatic hydrocarbons, steroids, and heavy metals. GSTM1 is located primarily in the liver, whereas GSTP1 is
located primarily in the brain and lungs.
The test indicates that the GSTM1 gene is present, although it is not clear whether the gene is present on one or
both chromosomes. This suggests normal GSTM1 enzyme activity and hepatic detoxification of xenobiotics and
toxic metals.
GSTP1 polymorphisms are associated with either higher or lower enzyme activity, depending on the exposure.
This genotype is associated with increased risk of various cancers, especially with cigarette smoke exposure. Risk
may also be increased for late-onset Alzheimer's, and Parkinson's disease in smokers.
Minimizing Risk: Minimize exposure to cigarette smoke, charred food, herbicides, fungicides, insect sprays,
industrial solvents, and toxic metals. Ensure availability of glutathione (GSH) precursors and cofactors, e.g.,
methionine, N-acetylcysteine, glutamine, glycine, magnesium, and pyridoxal-5-phosphate (B6). GSH depletion may
be reduced by alpha lipoic acid, milk thistle, and taurine. Allium vegetables (e.g., onions, leeks, garlic) and
crucifers (e.g., broccoli, cauliflower, cabbage, kale, Brussels sprouts, radish sprouts) can increase GST activity and
reduce cancer risk. Consume an antioxidant-rich diet to prevent oxidative stress.
+ + SOD2 A16V
Health Implications: Superoxide dismutase is the primary anti-oxidant enzyme within the mitochondria of cells
(where most of our energy is made). SOD2 converts reactive oxygen species into less reactive hydrogen peroxide.
Polymorphisms in SOD2 (+/- and +/+) are associated with reduced SOD activity. While this may increase some risk of
oxidative stress, more clinical correlations have been observed for the (-/-) genotype. This genotype has specifically
been associated with increased risk of cardiomyopathy.
Minimizing Risk: Although this genotype is less sensitive to antioxidant status compared to the (-/-) genotype, liberal
consumption of dietary antioxidants in colorful vegetables and fruits is still recommended. Broad-spectrum
antioxidant supplements may also be helpful, as well as manganese, which serves as a cofactor for SOD2. Consult
your health care provider to find the supplement regimen that best fits your overall health anti-oxidant needs.
