Breast cancer

The MTHFR Gene and Breast Cancer Risk

Author:
Anne Danahy, MS, RDN
Scottsdale, Arizona

 

Breast cancer is the most common form of cancer in women worldwide.1 Risk factors include alcohol use, obesity, inactivity, family history, and genetic mutations. The BRCA1 and BRCA2 mutations are well-known, but other genetic variants and single nucleotide polymorphisms (SNPs) also play a role in influencing one’s risk. SNPs are small mistakes, comparable to a spelling mistake, in a person’s genetic code. They can cause faulty cell growth or function that in some cases may favor the growth of cancer cells.

In two different studies in 2017, researchers identified a total of 72 common genetic variants that appear to increase the risk of breast cancer.2 While any one of these SNPs might increase the risk of breast cancer slightly, the study researchers suggest that the presence of several SNPs provides an additive effect. The risk is even further increased with the addition of other lifestyle risk factors, such as obesity or alcohol use.2

The MTHFR SNP and Breast Cancer

One common SNP often occurs in the gene that codes for methylenetetrahydrofolate reductase (MTHFR), an enzyme that is essential for the methylation of folate. Two variants of the MTHFR gene have been identified, and one, C677T, is thought to play a role in breast cancer. In the United States, approximately 25% of the Hispanic population and 10% to 15% of the white population have 2 copies of the C677T SNP.3

The MTHFR gene is critical for metabolizing folate or folic acid into its active methylfolate form. Methylfolate fuels methylation, the biochemical reaction that allows various metabolic cycles in the body to run normally, especially those that assist with repairing DNA, detoxifying the body, and producing the endogenous antioxidant glutathione.

Many studies that suggest that the MTHFR C677T SNP is associated with an increased risk of breast cancer in various populations, including Asian, Jewish, premenopausal, and postmenopausal women.4 The authors of one systematic review and meta-analysis examined data from 50 studies with 19,260 cases and 26,364 controls. They determined that the MTHFR C677T mutation appears to increase the risk of both breast cancer and ovarian cancer, especially among Asian women.5

It is unclear whether any additional risk is a result of the genetic mutation itself, lower methylfolate levels, less glutathione to defend against cancer cells, or some other factor. It is also important to note that not all research agrees with these findings. Data from some other studies do not support an association between MTHFR and breast cancer.

Advice for Patients

Genetic testing is an option to identify those with the MTHFR C677T SNP. In addition, high fasting blood levels of homocysteine may be suggestive of the SNP.3 Those who have the MTHFR SNP may benefit from taking a methylated form of folate, which does not have to be metabolized, since it is already in its active form. Adding more folate-rich foods such as leafy green vegetables, legumes, asparagus, Brussels sprouts, broccoli, and orange juice is one of the most important moves women can make to reduce their risk of breast cancer. A higher intake of folate-rich foods can result in more folate that is converted to its active form. Regardless of their MTHFR status, dietary folate intake is inversely associated with breast cancer risk.6,7

Finally, women who have, or are suspected to have the MTHFR C677T SNP should be assessed for other lifestyle risk factors that increase their risk of breast cancer, especially overweight or obesity, inactivity, and alcohol consumption, and be educated about ways to mitigate any additional genetic risk.

 

Anne Danahy, MS, RDN, is a registered dietitian nutritionist in Scottsdale, Arizona; a nutrition communications specialist; and author of Craving Something Healthy.

 

References:

  1. Breast cancer: prevention and control. World Health Organization. http://www.who.int/cancer/detection/breastcancer/en/. Accessed December 5, 2018.
  2. Study finds 72 new genetic mutations linked to breast cancer. Breastcancer.org https://www.breastcancer.org/research-news/72-new-genetic-mutations-linked-to-bc-found. Published October 24, 2017. Accessed December 6, 2018.
  3. MTHFR gene variant. National Institutes of Health, Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/10953/mthfr-gene-mutation. Accessed December 5, 2018.
  4. Liew S-C, Gupta ED. Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. Eur J Med Genet. 2015;58(1):1-10.
  5. He L, Shen Y. MTHFR C677T polymorphism and breast, ovarian cancer risk: a meta-analysis of 19,260 patients and 26,364 controls. Onco Targets Ther. 2017;10:227-238.
  6. Chen P, Li C, Li X, Li J, Chu R, Wang H. Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis. Br J Cancer. 2014;110(9):2327.
  7. de Batlle J, Ferrari P, Chajes V, et al. Dietary folate intake and breast cancer risk: European prospective investigation into cancer and nutrition. J Natl Cancer Inst. 2015;107(1):367.