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

Abstract

Background & Objective: Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism (OCM) 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 consisted of 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 tends to increase the BC metastasis.

Keywords

• breast cancer
• thymidylate synthase
• methionine synthase
• methionine synthase reductase
• polymorphism
• metastasis