Interactions Between MTHFR C677T - A1298C Variants and Folic Acid Deficiency Affect Breast Cancer Risk in a Chinese Population

Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients withbreast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosisunder folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer.
Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimatedby cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out.
Results: Theresults showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298Cand breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). TheMNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of thesingle variants (p < 0.05). At 15 to 60 nmol /L FA, the MNBN in cases with the TTAC genotype was higher thancontrols (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls afterexcluding the genetic background.
Conclusions: Associations between the combined MTHFR C677T-A1298Cpolymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosisin cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitiveto the genotoxic effects of FA deficiency than controls.