Abstract
Vitamin B12 has been widely related to methionine metabolism, which is an essential component for biological methylation reactions, including DNA methylation. However, the relationship between vitamin B12 and DNA methylation is still controversial. In addition, there is increasing evidence for the association between vitamin B12 and the risk of colorectal cancer (CRC), although results of this association need to be assessed with caution. For this purpose, we hypothesized that serum vitamin B12 could be associated with global DNA methylation in the CRC context. To test this hypothesis, we studied the association between global DNA methylation through long interspersed nuclear element-1 (LINE1) in CRC patients under the 25th percentile of serum vitamin B12. We found that the high vitamin B12 group had low LINE1 methylation in both tumor area and peripheral blood mononuclear cells (PBMCs) than the low serum vitamin B12 group. LINE1 methylation levels were significantly lower in tumor area compared to the adjacent tumor-free area, only in the high vitamin B12 group. LINE1 methylation in visceral adipose tissue (VAT) and PBMCs were correlated with tumoral, inflammatory, and insulin metabolism markers. However, the interaction between LINE1 methylation and vitamin B12 levels was associated with neoadjuvant therapy in the regression analysis only in men, suggesting a beneficial relationship. In conclusion, our results reported an inverse association between DNA methylation and vitamin B12 in the CRC context, which suggests that vitamin B12 may be implicated in an epigenetic state or mediation in CRC.
Highlights
Vitamin B12 plays essential roles in the metabolism of DNA methylation, through its participation in the homocysteine metabolism
We studied the association between methylation of long interspersed element-1 (LINE1) as a marker of global DNA methylation and serum vitamin B12 in different biological samples, such as peripheral blood mononuclear cells (PBMCs)—as a non-invasive source tissue, visceral adipose tissue (VAT)—as an active metabolic tissue, as well as tumoral tissues
long interspersed nuclear element-1 (LINE1) is typically found hypomethylated in colorectal cancer (CRC) [19,20], and tumor hypomethylation of LINE1 was significantly associated with worse overall survival and poor prognosis compared to patients with a higher level of LINE1 methylation in tumor [20]
Summary
Vitamin B12 plays essential roles in the metabolism of DNA methylation, through its participation in the homocysteine metabolism. It is required by the methionine synthase, a vitamin. Methionine, in turn, is converted to 5-adenosylmethionine, being an essential component for biological methylation. Previous studies have reported associations between vitamin B12 and DNA methylation [3]. Even a large-scale genome-wide DNA methylation study did not find correlation between vitamin B12 intake and DMPs [6]. The relationship between both dietary intake and supplementation with vitamin B12 and DNA methylation is still controversial. There is a lack of studies evaluating the link between serum levels of vitamin B12 and DNA methylation
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