The Association of Plasma Folate, Vitamin B12 and Homocysteine Levels on Hypermethylation Status of RARβ2 Gene in Primary Breast Carcinoma

The repression of retinoic acid receptor-β2 (RARβ2) expression is a concerning aspect of breast cancer, which is often induced by hypermethylation at promoter of the gene. We aimed to explore the correlation of plasma folate, vitamin B12 and total homocysteine (tHcy) levels with hypermethylation status of RARβ2 gene among Iranian breast cancer patients. The hypermethylation status was investigated in 137 specimens tissues from primary breast cancer patients aged 28-85 years thorough methylation-specific PCR. Hypermethylation at RARβ2 gene was observed in 36.5 %. The hypermthylated RARβ2 associated with younger age at diagnosis and negative family history of breast cancer. The plasma level of folate was found lower in cases aged ≥48 years with hypermethylated RARβ2 gene (P<0.05). In contrast the level of tHcy was shown higher in cases aged <48 y (P<0.05). The risk of hypermethylation at RARβ2 gene increased with low plasma levels of folate (OR=0.21, 95%CI: 0.05-0.88) and vitamin B12 (OR=0.04, 95%CI: 0.01-0.92) and high plasma level of tHcy (OR=7.55, 95%CI: 1.07-25.7) in cases older than 48y. Low plasma levels of folate, Vitamin B12 and high plasma level of total homocysteine could have important roles as prognostic factors in hypermethylation status of RARβ2 gene in breast cancer.