USDA Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas.
Cancer Res Commun. 2024 Jan 19;4(1):164-169. doi: 10.1158/2767-9764.CRC-23-0356.
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.
长期以来，人们一直在争论非遗传环境因素（如饮食）在多大程度上促成了癌症的发生。环境因素影响基因表达而不改变潜在 DNA 序列的一种潜在机制是表观遗传修饰。然而，饮食因素与致癌表观遗传调控之间的功能合作在很大程度上尚不清楚。在这里，我们使用年龄依赖性 p16 表突变的小鼠模型，其中 p16 基因活性直接受启动子 DNA 甲基化控制。我们表明，饮食补充中的叶酸和辅助因子可调节 p16 表突变，从而增加结肠癌的风险。重要的是，我们的发现为一般人群中叶酸强化的安全性提供了功能证据。
我们的研究表明，饮食中的叶酸和辅助因子可调节肿瘤抑制基因的甲基化，从而增加肠道肿瘤的发生。我们的发现强调了需要监测高危人群中叶酸强化的长期安全性。
