High levels of circulating folate concentrations are associated with DNA methylation of tumor suppressor and repair genes , , and in elderly Chileans.

BACKGROUND

Changes in DNA methylation, one of the most studied epigenetic mechanisms, are considered an initial marker for early cancer detection. We evaluated how availability of dietary factors (folates and vitamin B12) involved in one-carbon metabolism may contribute to DNA methylation changes of cancer-related genes in human subjects.

METHODS

We studied, by pyrosequencing, the methylation of tumor suppressor gene , DNA repair genes and , and the repetitive element LINE-1 (as a surrogate for global DNA methylation), in blood of elderly individuals ( = 249) who had been exposed to folic acid (FA) through FA-fortified wheat flour during the last 12 years.

RESULTS

We found that serum folate and to a lesser extent, vitamin B12 concentrations, were significantly correlated with DNA methylation of , , and , but not with . High serum folate concentrations (>45.3 nmol/L) were present in 31.1% of the participants. Although the methylated fraction of CpG sites in , , and was low (1.17-3.8%), high folate concentrations were significantly associated with methylation at the 3rd tertile of specific CpG sites in all genes with OR between 1.97 and 4.17.

CONCLUSIONS

This study shows that a public policy, like food fortification with FA that increases circulating serum folate levels, could affect methylation levels of specific genes linked to cancer risk. Our present results deserve additional studies to clarify the real impact of high FA levels for risk of cancer in a whole population chronically exposed to a fortified food such as wheat flour.

TRIAL REGISTRATION

ISRCTN 48153354 and ISRCTN 02694183.