Title | Dietary Folate and Cofactors Accelerate Age-dependent p16 Epimutation to Promote Intestinal Tumorigenesis. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Yang, L, Peery, RC, Farmer, LM, Gao, X, Zhang, Y, Creighton, CJ, Zhang, L, Shen, L |
Journal | Cancer Res Commun |
Volume | 4 |
Issue | 1 |
Pagination | 164-169 |
Date Published | 2024 Jan 19 |
ISSN | 2767-9764 |
Keywords | Animals, Carcinogenesis, Cell Transformation, Neoplastic, Cyclin-Dependent Kinase Inhibitor p16, Diet, Epigenesis, Genetic, Folic Acid, Humans, Intestinal Neoplasms, Mice |
Abstract | UNLABELLED: 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. |
DOI | 10.1158/2767-9764.CRC-23-0356 |
Alternate Journal | Cancer Res Commun |
PubMed ID | 38259096 |
PubMed Central ID | PMC10798135 |
Grant List | R01 HD100914 / HD / NICHD NIH HHS / United States R01 CA233472 / CA / NCI NIH HHS / United States R00 CA237618 / CA / NCI NIH HHS / United States P30 DK056338 / DK / NIDDK NIH HHS / United States P30 ES030285 / ES / NIEHS NIH HHS / United States P30 CA125123 / CA / NCI NIH HHS / United States |
Dietary Folate and Cofactors Accelerate Age-dependent p16 Epimutation to Promote Intestinal Tumorigenesis.
Similar Publications
A comparative study of structural variant calling in WGS from Alzheimer's disease families. Life Sci Alliance. 2024;7(5). | .
Genetic sex validation for sample tracking in next-generation sequencing clinical testing. BMC Res Notes. 2024;17(1):62. | .
The CARD8 inflammasome dictates HIV/SIV pathogenesis and disease progression. Cell. 2024;187(5):1223-1237.e16. | .