Breast Cancer and Genetic Factors: The Role of MTHFR in Risk Assessment

Breast Cancer and Genetic Factors: The Role of MTHFR in Risk Assessment

Breast cancer is one of the most common forms of cancer worldwide and the second leading cause of cancer-related death among women after lung cancer. [1] Although every woman is at some risk for breast cancer, the degree of risk for individual women can vary considerably. 

Research suggests that genes are the strongest hereditary risk factor for developing breast cancer, particularly in women who are affected at a younger age. In fact, around 10–20% of early-onset cases are hereditary. [2]

For this reason, women with a family history of breast cancer are strongly advised to be aware of their higher risks and seek regular checkups. 

This article will discuss the role of genetic factors in breast cancer, including the potential for the MTHFR gene to play a part. We will also cover how to manage your risks and support your health if you are affected by certain gene variants. 

Breast cancer: An overview:

Breast cancer accounts for about 12.5% of all new cancer cases worldwide and around 30% of all new cancer cases in women each year in the US. [3] About 13% of women will develop breast cancer some time during their lives. 

In 2020, there were an estimated 2.3 million new cancer cases and 685,000 cancer deaths (1 in 6 deaths) worldwide. An estimated 2,964,197 new female breast cancer cases are expected to occur in 2040 - a 31% increase from today. [4]

The most common symptoms of breast cancer include a lump in the breast (75% of women diagnosed), a change in shape and size of the breast (57%), a lump under the armpit (56%), and pain in one breast (56%). 

While the main risk factors for breast cancer include getting older and being a woman, many other factors are now known to be involved. Hormonal factors can increase the risk, including the age at which a woman starts menstruating and the density of her breasts throughout her lifetime. Previous cancer treatment may also increase the risk. However, genetic factors are also a significant contributor. 

Approximately 70% of women who develop breast cancer have cancerous tissue that has receptors for estrogen and/or progesterone. This is a form of cancer called hormone receptor-positive. Both estrogen and progesterone are related to cancer cell growth and spread. [5] Studies have shown that women with a family history of breast cancer are more likely to have ER (estrogen receptors) and PR (progesterone receptor) tumors than women without a family history. [6]

Connection between genes and breast cancer risk

Some studies suggest that first-degree relatives of individuals with breast cancer have triple the risk of developing cancer themselves. [7] Other studies indicate that up to 10% of all breast cancer cases are linked to genetic factors. In women aged under 30, genetic factors may account for up to 25% of cases. BRCA1 and BRCA2 are the 2 most important genes responsible for increased breast cancer susceptibility. [8]

People who inherit harmful variants in the genes BRCA1 (BReast CAncer gene 1) and BRCA2 (BReast CAncer gene 2) have increased risks of breast cancer and tend to develop cancer at younger ages than people who do not have these variants. However, studies suggest that around 55–72% of women with the BRCA1 mutation and 45–69% of women with the BRCA2 mutation will develop breast cancer before they turn 70. [9]

More recently, research has indicated a relationship between the MTHFR polymorphisms and the increased risk of breast cancer.

What is the MTHFR gene?

The MTHFR gene is involved in numerous essential processes within the body, including regulating folate levels, DNA synthesis, methylation, and tumorigenesis. [10] The MTHFR gene is also responsible for producing MTHFR, an enzyme that catalyzes and converts folic acid to methylfolate. 

The MTHFR enzyme is vital for proper folate metabolism and DNA biosynthesis, methylation, and repairing actively dividing cells. However, a common mutation - known as a SNP (single nucleotide polymorphisms) - often occurs in the MTHFR gene. There are two common variants of the MTHFR gene and of the two, the C677T variation is believed to play a role in the development of breast cancer.

Approximately 25% of the world’s population carries MTHFR C677T, some populations carry higher percentages, including 47% of Hispanics, 36% of Europeans, and 30% of East Asians. [11]

Poor function of the MTHFR enzyme leads to reduced levels of methylfolate, which in turn results in a lack of folate synthesis and DNA repair. Changes in the patterns of DNA methylation can lead to genetic faults - or mutations - that can then contribute to the process of carcinogenesis. [12]

Research has linked low folate levels and folate-related polymorphisms such as MTHFR to the incidence of cancer. [13] MTHFR polymorphisms have also been shown to influence the risk of breast cancer, with several studies showing a higher risk of incidence of breast cancer in individuals with MTHFR. [14] This appears to be more prevalent in Caucasian and Asian populations. 

The MTHFR C677T mutation appears to increase the risk of both breast cancer and ovarian cancer, especially among Asian women.

Women with active ovulatory cycles who also have MTHFR gene mutations are most at risk for breast cancer. [15] However, scientists are not yet certain if the mutation itself causes cancer, or if it simply increases the risk by reducing methylfolate and/or glutathione to defend against cancer cells, or other factors. Further research is pending. 

Prevention and awareness

Many factors contribute to the development of breast cancer, and include both environmental and genetic factors. The most common of these are age, diet, body mass index (BMI), reproductive history, common oncogenes, breast density, and family history. [16] However, research suggests that many risks can be modified, particularly diet, exercise; avoiding smoking, alcohol and drugs, and supporting healthy hormonal balance. [17]

Tips on breast cancer prevention


Obesity has been linked to many cancers, including breast cancer. [18]

Eating a diet rich in antioxidants - particularly Vitamin C and vitamin E - can help protect against breast cancer risk. Vitamin E has been shown to reduce the number of carcinogen-induced mammary tumors in animals. [19] Recommended diets include the DASH diet and the Mediterranean diet, which are rich in vegetables, fruits, fish, whole grains, and unsaturated fats from nuts and extra-virgin olive oil. [20]

Supporting your folate levels by eating plenty of folate-rich foods can also help support healthy cell repair in the body. For additional support, consider supplementing with methylfolate, active B12, and other nutrients required by the body for proper methylation and DNA synthesis. 


Numerous studies have reported the importance of physical activity in preventing breast cancer. Women can reduce their risk of developing cancer by 25–30% if they exercise regularly. Being active also helps in recovering from breast cancer, both during and after treatment. [21]

While any amount of exercise is beneficial, most studies recommend at least 30-60 min/day five days a week. This can include brisk walking, running, swimming, cycling, or any other activity that increases the heart rate. 

Awareness of family history

Family history is one of the most well-known factors in the development of breast cancer. Around 5–10% of women diagnosed have a family member who has also had breast cancer. [22]

Faulty genes can increase the risk of breast cancer. Normally, the BRCA1 and BRCA2 genes stop cells in the body from growing and dividing out of control. However, a mutation on the gene can lead to cells multiplying and developing into various cancers, including breast cancer.

BRCA1 mutations occur in around 7% of families with a history of breast cancer, while BRCA2 mutations are found in about 20% of families at high risk for both breast and ovarian cancers. [23]

Anyone who has a family history of breast cancer or is concerned that they may have a harmful BRCA1 or BRCA2 gene should speak to their healthcare provider. Testing can identify risk factors for potential gene variants

The role of regular screening and mammograms

While no test is 100% accurate, regular mammograms can reduce the risk of dying from breast cancer. Early detection of breast cancer may mean more efficient treatment and less time spent recovering. [24]

Self-examination is also an important and effective means of prevention. Regularly checking your breasts will help you identify any changes or abnormalities such as lumps or skin changes. You can then report any changes to your healthcare provider right away.

The takeaway

While every woman is at risk for developing breast cancer, there are ways to reduce that risk - even when genetic links are present. 

The first step is to be aware of your risk. If you have relatives who have had any form of cancer or any other genetic mutations - including the MTHFR mutation - it’s essential that you monitor your own health throughout life. Have regular checkups. This includes both mammograms and self-examinations. Maintain a healthy lifestyle with a nutritious diet, regular exercise, and limiting harmful factors such as alcohol and smoking. 

When in doubt, consult a qualified healthcare practitioner. 




























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