Variants of Genes Involved in Metabolism of Folate among Patients with Breast Cancer: Association of TYMS 3R Allele with Susceptibility to Breast Cancer and Metastasis

Background & objective Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism disturbance might play an important role in the etiology of BC. The present study aimed to investigate the thymidylate synthase (TYMS), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and methionine synthase reductase (MTRR) variants as good candidates for studying the role of genetic variants of folate metabolizing enzymes in the risk of BC. Methods The present case-control study includes 100 BC patients and 141 healthy females. The TYMS 2R/3R (rs34743033), MTR c.2756A>G (rs1805087), and MTRR c.66A>G (rs1801394) variants were detected by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and a designed amplification-refractory mutation system (ARMS) method, respectively. Results The 3R allele of TYMS enhanced the risk of BC by 2.84-fold (P G and MTRR c.66A>G variants were not significantly different among patients and controls. Conclusion We observed that the TYMS 3R is a risk allele for susceptibility to BC and this allele may increase the risk of metastasis in BC patients. .