DNA methylation, cancer susceptibility, and nutrient interactions.
DNA methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of cancer. Aberrant methylation of DNA (global hypomethylation accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can result in chromosome instability, and hypermethylation has been associated with the inaction of tumor suppressor genes. Preclinical and clinical studies suggest that part of the cancer-protective effects associated with several bioactive food components may relate to DNA methylation patterns. Dietary factors that are involved in one-carbon metabolism provide the most compelling data for the interaction of nutrients and DNA methylation because they influence the supply of methyl groups, and therefore the biochemical pathways of methylation processes. These nutrients include folate, vitamin B(12), vitamin B(6), methionine, and choline. However, looking at individual nutrients may be too simplistic. Dietary methyl (folate, choline, and methionine) deficiency in combination causes decreased tissue S-adeno-sylmethionine, global DNA hypomethylation, hepatic steatosis, cirrhosis, and ultimately hepatic tumorigenesis in rodents in the absence of carcinogen treatment. Other dietary components such as vitamin B(12), alcohol, and selenium may modify the response to inadequate dietary folate.
Davis
Cindy D
CD
Nutritional Sciences Research Group, Division of Cancer Prevention, National Cancer Institute, 6130 Executive Boulevard, Suite 3159, Rockville, MD 20892-7328, USA. davisci@mail.nih.gov.
Uthus
Eric O
EO
D000818:Animals; D002796:Choline Deficiency / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D003677:Deficiency Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004032:Diet; D004198:Disease Susceptibility; D005492:Folic Acid / Q000008:administration & dosage; D005494:Folic Acid Deficiency / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008715:Methionine / Q000172:deficiency / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics; D012643:Selenium / Q000008:administration & dosage / Q000172:deficiency
D005492:Folic Acid; D008715:Methionine; D012643:Selenium