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 with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under 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 estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out.


RESULTS
The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and 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). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p<0.05). At 15 to 60 nmol /L FA, the MNBN in cases with the TTAC genotype was higher than controls (p<0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background.


CONCLUSIONS
Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls.
School of Life Sciences, Yunnan University, Kunming, China.
Xia-Yu
XY
Wu
Juan
J
Ni
Wei-Jiang
WJ
Xu
Tao
T
Zhou
Xu
X
Wang
D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D005260:Female; D005494:Folic Acid Deficiency / Q000150:complications* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors
D042965:Methylenetetrahydrofolate Reductase (NADPH2)