Publication Date
1-19-2024
Journal
Cancer Research Communications
DOI
10.1158/2767-9764.CRC-23-0356
PMID
38259096
PMCID
PMC10798135
PubMedCentral® Posted Date
1-19-2024
PubMedCentral® Full Text Version
Post-Print
Published Open-Access
yes
Keywords
Animals, Humans, Mice, Carcinogenesis, Cell Transformation, Neoplastic, Diet, Epigenesis, Genetic, Folic Acid, Intestinal Neoplasms, Cyclin-Dependent Kinase Inhibitor p16
Abstract
The extent to which non-genetic environmental factors, such as diet, contribute to carcinogenesis has been long debated. One potential mechanism for the effects of environmental factors is through epigenetic modifications that affect gene expression without changing the underlying DNA sequence. However, the functional cooperation between dietary factors and cancer-causing epigenetic regulation is largely unknown. Here, 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.
SIGNIFICANCE: Our study demonstrates that dietary folate and cofactors modulate tumor-suppressor gene methylation to increase intestinal tumorigenesis. Our findings highlight the need for monitoring the long-term safety of folate fortification in high-risk individuals.
Comments
Associated Data