Dietary folate and cofactors accelerate age-dependent p16 epimutation to promote intestinal tumorigenesis

We use a mouse model of age-dependent p16 epimutation, in which the p16 gene activity is directly controlled by promoter DNA methylation. We show p16 epimutation is modulated by folate and cofactors in dietary supplementation, which leads to increased colon cancer risk. Importantly, our findings provide functional evidence concerning the safety of folate fortification in the general population. As a control, we analyzed cells from adjacent normal colonic mucosa.