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 ethyltransferase (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<0.001). in the presence of tyms 3r/3r, compared to tyms 2r/3r, there was a trend toward enhancing the risk of metastasis by 4.15-fold (95% ci: 0.96-17.85, p=0.055). the frequencies of mtr c.2756a>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.