Epigenetic modifications and human pathologies: cancer and CVD.
Epigenetic changes are inherited alterations in DNA that affect gene expression and function without altering the DNA sequence. DNA methylation is one epigenetic process implicated in human disease that is influenced by diet. DNA methylation involves addition of a 1-C moiety to cytosine groups in DNA. Methylated genes are not transcribed or are transcribed at a reduced rate. Global under-methylation (hypomethylation) and site-specific over-methylation (hypermethylation) are common features of human tumours. DNA hypomethylation, leading to increased expression of specific proto-oncogenes (e.g. genes involved in proliferation or metastasis) can increase the risk of cancer as can hypermethylation and reduced expression of tumour suppressor (TS) genes (e.g. DNA repair genes). DNA methyltransferases (DNMT), together with the methyl donor S-adenosylmethionine (SAM), facilitate DNA methylation. Abnormal DNA methylation is implicated not only in the development of human cancer but also in CVD. Polyphenols, a group of phytochemicals consumed in significant amounts in the human diet, effect risk of cancer. Flavonoids from tea, soft fruits and soya are potent inhibitors of DNMT in vitro, capable of reversing hypermethylation and reactivating TS genes. Folates, a group of water-soluble B vitamins found in high concentration in green leafy vegetables, regulate DNA methylation through their ability to generate SAM. People who habitually consume the lowest level of folate or with the lowest blood folate concentrations have a significantly increased risk of developing several cancers and CVD. This review describes how flavonoids and folates in the human diet alter DNA methylation and may modify the risk of human colon cancer and CVD.
Nutrition and Epigenetics Group, Division of Vascular Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK. s.duthie@abdn.ac.uk
Susan J
SJ
Duthie
D002318:Cardiovascular Diseases / Q000235:genetics* / Q000517:prevention & control; D019175:DNA Methylation / Q000502:physiology*; D004032:Diet; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use; D005492:Folic Acid / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000517:prevention & control; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D059808:Polyphenols; D011519:Proto-Oncogenes; D014803:Vitamin B Complex / Q000494:pharmacology / Q000627:therapeutic use
D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D014803:Vitamin B Complex; D005492:Folic Acid