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INTERNATIONAL CONGRESS OF

CancerGenetics

• Association between dietary folate intake and genetic mutations that cause breast cancer

• Zahra Mirzaei,¹ mahdi soltanian,^2,*
  1. Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran
  2. Student Research Committee, Semnan University of Medical Sciences, Semnan, Iran
  
  
  
• Introduction: Breast cancer (BC) is the most diagnosed malignancy worldwide and is a leading cause of half million women deaths annually. Some of the related risk factors that we can name for this disease are menarche, age of first birth or menopause, breastfeeding, excess weight, low physical activity, alcohol consumption, viral infectious agent, and gene mutations. Women who inherit a deleterious BRCA1-2 or MTHFR gene mutations are at risk of developing BC. Evidence shows that there is U-shaped relationship between levels of folate in diet and serum with breast cancer risk. So that both low and high levels of folate in plasma may increase risk of breast cancer, whereas midrange intakes are protective. the issues that are important regarding the intake of folate supplements are the dose and stage of cell transformation at the time of intervention.
• Methods: Studies published updated to July 2024 analyzing "the effect of folate on breast cancer related genes" were searched by searching Google Scholar, Pubmed, and Web of Science. Among the screened articles, related articles were reviewed.
• Results: The proteins encoded by BRCA1 and BRCA2 are critical checkpoints in cell cycle for repair of single- and double-stranded DNA breaks with homologous recombination, and repairing of stalled or collapsed replication forks. If these genes are mutated, they may disrupt normal cell cycle and lead to carcinoma. Germline genetic mutations in BRCA1 are one hallmark of hereditary BC. Folate is a key factor in one-carbon metabolism, the universal source of methyl donors for DNA methylation that plays important roles in nucleotide biosynthesis and biological methylation reactions. BRCA1 and BRCA2 mutation carriers are more sensitive to folate deficiency-induced genome damage, especially those who develop breast cancer. So adequate folate status may be necessary for the protection of genomic stability and the prevention of BC. Evidence supports that the risk of BC in women who only had mutations in their BRCA1 gene and used folic acid-containing supplements was significantly decreased, compared to women who never used a folic acid-containing supplement. In the other hand Folate status affects DNA methylation by interacting with the MTHFR C677T polymorphism. MTHFR is a crucial enzyme in folate metabolism, facilitating the conversion of 5,10-methylenetetrahydrofolate to 5-methylenetetrahydrofolate, a methyl donor that is essential for DNA functions. Also Folate may increase breast cancer risk by promoting the silencing of tumor-suppressor genes APC, PTEN, and RARb2 through DNA methylation. Excessive folate intake can disrupt one-carbon metabolism, potentially contributing to breast cancer development.
• Conclusion: Since excessive and deficient folate levels are both carcinogens, dietary folate intake should be arranged in normal range by considering suitable dietary patterns (that have enough folate resources) and cooking methods. More researches and studies with large sample size and long follow-up periods are needed to provide more knowledge about relation between folate status and breast cancer risk in high-risk women and suggest ways to control it.
• Keywords: Breast cancer, BRCA1/2, MTHFR, "folate"