Association between dietary intake of folate, vitamin B(6), B(12) & MTHFR, MTR Genotype and breast cancer risk

Objective: we conducted a case-control study to investigate the association between dietary folate, vitamin B(6) and vitamin B(12) 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 B(6) and vitamin B(12) 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 B(6) (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 B(6) 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 B(6) and breast cancer risk, and a significant interaction was observed between MTHFR C667T polymorphism and folate intake on the risk of breast cancer.