Association of plasma folate, vitamin B12 and homocysteine levels with hypermethylation status of ERα gene in primary breast carcinoma

The translation of estrogen receptor-α (ERα) is vital in therapeutic regimens in breast cancer. The repression of its expression could be attributed to regional CpG island methylation in exon1. We aimed to explore the association of plasma levels of folate, vitamin B12 and total homocysteine (tHcy) with the hypermethylation status of ERα genes in breast cancer patients. The hypermethylation status was determined in dissected tissues from 137 primary breast cancer patients aged 28-85 years, using methylation-specific PCR. In addition, the plasma levels of folate and vitamin B12 of the patients were assessed by automated chemiluminescence, and their total plasma homocysteine was determined by HPLC. The logistic regression analysis was used for analyzing the data after adjusting for potential confounding factors. Hypermethylation at ERα was observed in 51.1% of the participants. It was related positively to smoking history and duration of exposure to estradiol, and inversely with ER translation. After adjustments for confounding factors, an inverse association was also found between the hypermethylation status of ERα gene and the plasma levels of folate (OR=0.187; 95%CI, 0.052-0.668) and vitamin B12 (OR=0.185; 95%CI, 0.036-0.953). The data also showed that the risk of hypermethylation at ERα gene increased with the high plasma levels of tHcy (OR=9.61; 95%CI, 1.26-73.2). It may be concluded that a high plasma tHcy level can potentially increase the risk of hypermethylation of the ERα gene, while plasma folate and vitamin B12 levels may reduce the risk, in cancer patients