The gene mutation MTHFR and its role in cancer
A key component of methylating processes that occur within every cell of the human body is the gene MTHFR (methylenetetrahydrofolate reductase). MTHFR acts comparable to a switch turning biological activities off and on in the body.
This concept is known as epigenetics and is vastly opposite the old belief that our biological inheritance is unchangeable. These modifications that are made to our genes has received considerable attention in the most recent decade and is associated with cancer development.
The role of methylation
Methylation pathways are stimulated trillions of times every minute within every cell. Methylation involves transferring methyl groups to amino acids, enzymes, DNA and proteins to body tissue. It is a critical metabolic process essential for living and involves a series of reactions that pass along these methyls “on / off” switches.
Genes which suppress tumors can be inactivated by DNA methylation. Under optimal methylating pathways, glutathione is produced which is a powerful antioxidant that supports our body’s healing abilities.
Proper methylation promotes the following healthy functions: (1)
- Histamine tolerance
- Stress management
- Nerve protection or neurotransmitter myelination
- Protection and repair of DNA and RNA
David Jockers DNM, DC, MS is a doctor of natural medicine, functional nutritionist, and corrective care chiropractor. He owns and operates Exodus Health Center in Kennesaw, Georgia.
MTHFR interacts with methylation
Both folate and one-carbon metabolism are reliant on the MTHFR gene. DNA synthesis is dependent on one-carbon metabolism as well as converting homocysteine into SAM (S-adenosyl methionine) (2). Optimal DNA, RNA and protein methylation is required from the methyl donating properties of SAM.
The enzymeA protein that speeds up chemical reactions in the body. 5, 10- methylenetetrahydrofolate reductase is folate metabolizing and is also involved in synthesizing SAM and regulating DNA synthesis.
Disruptions to MTHFR increases cancer risk
Disrupting the MTHFR gene can directly increase the likelihood of cancer development. When the levels of molecules that function as precursors to methionine conversion are above normal, the biological pathways of converting homocysteine into methionine are adversely impacted. For example, uracil may be used at exceedingly high concentrations instead of thymine. The increased risk of damage to DNA and genetic mutation occurs with this sort of continual genetic change.
SAM necessitates methylation pathways in DNA. When methionine is altered, both DNA and genetic expression may be altered. When MTHFR is less active, hypomethylation occurs resulting from low SAM levels (4). This loss of methyl groups disrupts the body’s requirement to prioritize methyl groups based on immediate concerns.
This phenomenon known as hypomethylation was first recognized in 1983. However, the negative effects on the body when the demand for methyl groups is higher than what is available has not been understood since the 21st century. Hypomethylation significantly increases carcinogenic tissue growth and cancer metastasisThe spread of cancer cells from the place where they first formed to another part of the body. In metastasis, cancer cells break away from the original (primary) tumor, travel through the blood or lymph system, and form a new tumor in other organs or tissues of the body. The new, metastatic tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the lung, the cancer cells in the lung are breast cancer cells, not lung cancer cells.. We have since learned that hypomethylation is present in all forms of cancer and it increases with tumor progression further stimulating cancerous activity. (4)
Polymorphisms and cancer risks
Two genes are most commonly linked to increased cancer risk involving MTHFR. Polymorphism C677T and A1298C are dependent on every individual’s genetic makeup and their genetic prevalence within ethnic groups.
A polymorphism is a variation which naturally occurs within a genetic sequence or chromosome alteration. Both genetic predisposition and environmental influences are therefore also associated with polymorphism and cancer risks. (6)
The MTHFR C677T polymorphism is most common and occurs when the amino acid alanine is swapped instead with valine. This seemingly insignificant change produces major consequences. The result is an MTHFR enzyme with the ability to only handle 30 percent of its otherwise normal responsibilities when alanine is properly encoded in the gene.
Common cancers with polymorphism MTHFR C677T and A1298C
Breast cancer — Studies have shown that breast cancer risks reduce with increased folate consumption. When optimal levels of folate are included in one’s diet, breast cancer risk significantly reduces.
Polymorphism C677T may even be linked with the age of menstruation and the childbearing of a woman's first child. Although further studies must be conducted, some research shows that breast cancer risk increases with late childbearing and the delayed onset menarche. (3)
Breast cancer involves one million new diagnoses each year and regardless of other risk factors, abnormal MTHFR is a known precursor to breast cancer (4).
Gastric cancer — Conflicting data suggests whether C677T polymorphism is associated with the elevated risk of gastric cancer. However, some research has found that this genetic variance is higher in Asian populations when compared to Caucasian. There is a higher percentage of the abnormal allele in individuals in Korea and East Asia and there is also a higher prevalence of gastric cancer. (5)
The risk for gastric cancer applies equally to anyone with the abnormal allele, yet individuals from Asian descent have a higher risk of carrying the genetic variance.
Prostate and testicular cancer — The risk seems to vary among different populations but hypomethylation is linked to a higher risk of prostate and testicular cancers. Polymorphisms C677T and a1298C aggravate nutrient disturbance in the metabolism of both folate and Vitamin B12 serum concentrations. This risk may again be greatest in East Asian populations. (8)
Other cancers — There is still a vast amount of understanding that must be learned regarding the consequences of MTHFR gene mutations and cancer risks. However, MTHFR gene polymorphisms have been linked to childhood leukemia, and cancer of the skin, lung, head, neck and colon.
Improve your body’s methylating abilities
Reduce your risk of developing cancer by improving your body’s natural methylation processes. It is recommended to regularly detoxify all of the organs and the body. Managing stress is also critical because chronic stress depletes methyl groups from required biological functions.
- Receive healthy amounts of sleep
- Limit exposure to all environmental contaminants
- Increase dietary antioxidantsProtects cells from damage caused by free radicals (unstable molecules made by the process of oxidation during normal metabolism). Free radicals may play a part in cancer, heart disease, stroke, and other diseases of aging. Antioxidants include beta-carotene, lycopene, Vitamins A, C, and E, and other natural and manufactured substances. by consuming fruits and veggies rich
- Increase consumption of dark leafy greens and lentils naturally rich in folate
- Eliminate, if not avoid, all inflammatory foods including sugar and common inflammation-promoting allergy triggers such as dairy, gluten, and soy
- MTHFR Support Link Here
- Lucock M, et al. Methylation diet and methyl group genetics in risk for adenomatous polyp occurrence. BBA Clin. 2015 Jan; 107-12. PMID: 26673393
- Zhang XF, et al. Association between MTHFR 677C/T and 1298A/C gene polymorphisms and breast cancer risk. Genet Mol Res. 2015 Dec; 14(4): 16425-30. PMID: 26662439
- Kumar P, Yadav U, and Rai V. Methylenetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility. Meta Gene. 2015 Oct; 6: 72-84. PMID: 26629412
- Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics. 2009 Dec; 1(2): 239-259. PMID: 2873040
- Chen L, et al. Association between the MTHFR C677T polymorphism and gastric cancer susceptibility: A meta-analysis of 5,757 cases and 8,501 controls. Oncol Lett. 2015 Aug; 10(2): 1159-1165. PMID: 26622644
- NIH: Genetics Home Reference Link Here
- Chen PL, et al. Association between mtHFR gene polymorphisms (C677T, A1298C) and genetic susceptibility to prostate cancer: a meta-analysis. Genet Mol Res. 2015 Dec; 14(4): 19191-202. PMID: 26782572