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Epigenetic modifications and human pathologies: cancer and CVD

  • Susan J. Duthie (a1)
  • DOI:
  • Published online: 11 November 2010

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.

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Correspondence author: Dr Susan J. Duthie, fax +44 1224 716629, email
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1.PA Jones & SB Baylin (2007) The epigenomics of cancer. Cell 128, 683692.

2.MP Turunen , E Aavik & S Yla-Herttula (2009) Epigenetics and atherosclerosis. Biochim Biophys Acta 1790, 886891.

3.MF Fraga , E Ballestar , MF Paz (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102, 1060410609.

5.DC Dolinoy (2008) The agouti mouse model: an epigenetic biosensor for nutritional and environmental alterations on the fetal epigenome. Nutr Rev 66 (Suppl. 1), S7–S11.

6.SA Ross , J Dwyer , A Umar (2008) Diet, epigenetic events and cancer prevention. Nutr Rev 66 (Suppl. 1), S1S6.

7.RH Dashwood & E Ho (2008) Dietary agents as histone deacetylase inhibitors: sulforaphane and structurally related isothiocyanates. Nutr Rev 66 (Suppl. 1), S36S38.

8.N Druesne-Pecollo , C Chaumontet & P Latino-Martel (2008) Diallyl disulfide increases histone acetylation in colon cells in vitro and in vivo. Nutr Rev 66 (Suppl. 1), S39S41.

9.I Rahman (2008) Dietary polyphenols mediated regulation of oxidative stress and chromatin remodeling in inflammation. Nutr Rev 66 (Suppl. 1), S42S45.

11.JF Costello & C Plass (2001) Methylation matters. J Med Genet 38, 285303.

12.F Gaudet , JG Hodgson , A Eden (2003) Induction of tumors in mice by genomic hypomethylation. Science 300, 489492.

13.IT Johnson & NJ Belshaw (2008) Environment, diet and CpG island methylation: epigenetic signals in gastrointestinal neoplasia. Food Chem Toxicol 46, 13461359.

14.RP Arasaradnam , DM Commane , D Bradburn (2008) A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis. Epigenetics 3, 193198.

16.LR Ferguson (2001) Role of plant polyphenols in genomic stability. Mutat Res 475, 80111.

17.SJ Duthie (2007) Berry phytochemicals, genomic stability and cancer: evidence for chemoprotection at several stages in the carcinogenic process. Mol Nutr Food Res 51, 665674.

20.WJ Lee , JY Shim & BT Zhu (2005) Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids. Mol Pharmacol 68, 10181030.

23.K Kato , NK Long , H Makita (2008) Effects of green tea polyphenol on methylation status of RECK gene and cancer cell invasion in oral squamous cell carcinoma cells. Br J Cancer 99, 647654.

24.JC Chuang , CB Yoo , JM Kwan (2005) Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-aza-2′-deoxycytidine. Mol Cancer Ther 4, 15151520.

25.C Stressman , B Brueckner , Musch (2006) Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res 66, 27942800.

29.CJ Boushey , SAA Beresford , GS Omenn (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 274, 10491057.

35.The Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 288, 20152022.

38.The Heart Outcomes Prevention Evaluation (HOPE)2 Investigators (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. NEJM 354, 15671577.

39.S Voutilainen , TA Lakka , E Porkkala-Sarataho (2000) Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Eur J Clin Nutr 54, 424428.

41.SN Doshi , IFW McDowell , SJ Moat (2002) Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering. Circulation 105, 2226.

42.M Usui , H Matsuoka , H Miyazaki (1999) Endothelial dysfunction by acute hyperhomocysteinemia: restoration by folic acid. Clin Sci 96, 235239.

44.IP Pogribny , SJ James , S Jernigan (2004) Genomic hypomethylation is specific for preneoplastic liver in folate/methyl deficient rats and does not occur in non-target tissues. Mutat Res 548, 5359.

45.JM Stempak , K-Y Sohn , E-P Chiang (2005) Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model. Carcinogenesis 26, 981990.

47.SJ Duthie , S Narayanan , S Blum (2000) Folate deficiency in vitro induces uracil misincorporation, DNA hypomethylation and inhibits DNA excision repair in immortalised normal human colon epithelial cells. Nutr Cancer 37, 127133.

52.Y-J Sohn , JM Stempack , S Reid (2003) The effect of dietary folate on genomic and p53-specific DNA methylation in rat colon. Carcinogenesis 24, 8190.

53.SJ Duthie , S Narayanan , GM Brand (2000) DNA stability and genomic methylation status in colonocytes isolated from methyl-donor-deficient rats. Eur J Nutr 39, 106111.

59.M Fenech , C Aitken & J Rinaldi (1998) Folate, vitamin B12, homocysteine status and DNA damage in young Australian adults. Carcinogenesis 19, 11631171.

62.M Cravo , P Fidalgo , AD Pereira , . (1994) DNA methylation as an intermediate biomarker in colorectal cancer: modulation by folic acid supplementation. Eur J Cancer Prev 3, 473479.

63.ML Cravo , AG Pinto , P Chaves . (1998) Effect of folate supplementation on DNA methylation of rectal mucosa in patients with colonic adenomas: correlation with nutrient intake. Clin Nutr 17, 4549.

64.GP Basten , SJ Duthie , LP Pirie (2006) Sensitivity of markers of DNA stability and DNA repair activity to folate supplementation in healthy volunteers. Br J Cancer 94, 19421947.

65.MO Hiltunen , MP Turunen , TP Hakkinen (2002) DNA hypomethylation and methyltransferase expression in atherosclerotic lesions. Vasc Med 7, 5–11.

66.G Lund , L Andersson , M Lauria (2004) DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking Apolipoprotein E. J Biol Chem 279, 2914729154.

67.WS Post , PJ Goldschmidt-Clermont , CC Wilhide (1999) Methylation of the estrogen receptor gene is associated with aging and atherosclerosis in the cardiovascular system. Cardiovasc Res 43, 985991.

68.AK Ying , HH Hassanain , CM Roos (2000) Methylation of the estrogen receptor-α gene promoter is selectively increased in proliferating human aoric smooth muscle cells. Cardiovasc Res 46, 172179.

69.MO Hiltunen & S Yla-Herttuala (2003) DNA methylation, smooth muscle cells and atherogenesis. Arterioscler Thromb Vasc Biol 23, 17501753.

70.Z Chen , AC Karaplis , SL Ackerman (2005) Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity within neuropathology and aortic lipid deposition. Hum Mol Genet 10, 433443.

72.P Yi , S Melnyk , M Pogribna (2000) Increase in plasma homocysteine associated with parallel increase in plasma S-adenosyl homocysteine and lymphocyte DNA hypomethylation. J Biol Chem 275, 2931829323.

73.KS Brown , Y Huang , Z-Y Lu (2006) Mild folate deficiency induces a proatherosclerotic phenotype in endothelial cells. Atherosclerosis 189, 133141.

74.MA Hoffman , E Lalla , Y Lu (2001) Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest 107, 675683.

75.J Zhou , J Moller , CC Danielsen (2001) Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 21, 14701476.

76.J Zhou , J Moller , M Ritskes-Hoitinga (2003) Effects of vitamin supplementation and hyperhomocysteinemia on atherosclerosis in ApoE-deficient mice. Atherosclerosis 168, 255262.

77.AM Troen , E Lutgens , DE Smith (2003) The atherogenic effect of excess methionine intake. Proc Natl Acad Sci USA 100, 1508915094.

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