American Association for Cancer Research
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Figure S3 from Dietary Folate and Cofactors Accelerate Age-dependent p16 Epimutation to Promote Intestinal Tumorigenesis

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posted on 2024-01-19, 14:20 authored by Li Yang, Robert C. Peery, Leah M. Farmer, Xia Gao, Yiqun Zhang, Chad J. Creighton, Lanjing Zhang, Lanlan Shen

Supplementary Figure S3 shows dietary methyl donor supplementation markedly increases tumor cell proliferation and immune cell infiltration.

Funding

USDA | Agricultural Research Service (ARS)

HHS | NIH | National Cancer Institute (NCI)

HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

HHS | NIH | All of Us Research Program

Cancer Prevention and Research Institute of Texas (CPRIT)

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)

History

ARTICLE 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. 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.