The Role of Folic Acid in DNA Methylation and Breast Cancer

Folate and folic acid (FA) are two forms of vitamin B9, a B-complex nutrient essential for the human body. Folate is the natural form of vitamin B9 and is found in foods such as citrus fruits, leafy green vegetables, and beans. In contrast, FA is the synthetic form and is commonly found in supplements and added to fortified foods. The metabolism of folate and FA plays a crucial role in DNA synthesis and methylation; therefore, understanding the mechanism through which a decrease in folate and FA consumption affects the development of breast cancer (BC) is important. DNA hypermethylation can inhibit the transcription of tumor suppressor genes, while DNA hypomethylation may have the same effect and activate oncogene transcription. However, some genetic variants exist, such as rs1801133 and rs1801131 in the MTHFR gene and rs1051266 in the RFC gene. The MTHFR gene encodes an enzyme that facilitates the utilization of folate to support essential bodily functions, while the RFC gene is responsible for transporting folate into cells and acts as an anion exchanger. Both genes intervene in the transport and absorption of FA and are related to an increased risk of cancer. Studies investigating the relationship between FA and BC often rely on in vitro and in vivo models; however, the findings may not fully translate to humans due to significant physiological and metabolic differences across species. This article explores how changes in FA metabolism due to malabsorption defects, a deficient diet or genetic variants may impact methylation processes and their relationship with BC.