Variants of Genes Involved in Metabolism of Folate Among Patients with Breast Cancer: Association of 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  2R/3R (rs34743033),  c.2756A>G (rs1805087), and 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 enhanced the risk of BC by 2.84-fold (<0.001). In the presence of 3R/3R, compared to 2R/3R, there was a trend toward enhancing the risk of metastasis by 4.15-fold (95% CI: 0.96-17.85, =0.055). The frequencies of c.2756A>G and c.66A>G variants were not significantly different among patients and controls.

CONCLUSION

We observed that the 3R is a risk allele for susceptibility to BC and this allele may increase the risk of metastasis in BC patients. .