Association between dietary intake of folate, vitamin B6, B12 & MTHFR, MTR Genotype and breast cancer risk

OBJECTIVE we conducted a case-control study to investigate the association between dietary folate, vitamin B6 and vitamin B12 intake, MTHFR and MTR genotype, and breast cancer risk. METHODS Genotyping for MTHFR C677T and A1298C and MTR A2756G polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) method. The intake of folate, vitamin B6 and vitamin B12 were calculated by each food item from questionnaire. RESULTS Subjects with breast cancer tended to have more first-degree relatives (χ(2) =30.77, P<0.001) and have high intake of folate (t=2.42, P=0.008) and Vitamin B6 (t=2.94, P=0.002). Compared to the reference group, women with MTHFR 677 TT genotype and T allele had a significantly increased risk of breast cancer, with ORs (95%CI) of 1.8(1.08-2.27) and 1.39(1.02-1.92), respectively. For those who had folate intake＜450 ug/day, MTHFR 667TT genotype was associated with a higher risk of breast cancer (OR=2.45, 95% CI=1.09-5.82, P=0.02). Similarly, subjects with Vitamin B6 intake＜0.84 mg/day and MTHFR 667T allele genotype was correlated with a marginally increased risk of breast cancer. A significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer (P for interaction was 0.025). CONCLUSION This case-control study found a significant association between MTHFR C667T polymorphism, folate intake and vitamin B6 and breast cancer risk, and a significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer.