Epigenetic modifications and human pathologies: cancer and CVD

Abstract

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.

Oxidative Stress and Antioxidants in Disease and Cancer: A Review

“…The regulation of gene expression by dietary polyphenols in cellular models such as the vascular endothelial cells is evident (Nicholson et al, 2010). One of the noteworthy current discoveries that have emerged from the phytochemical-antioxidant interactions in mammalian model systems is their nature of modulating the mammalian epigenome (Duthie, 2011). Totally, novel disciplines such as nutrigenetics and nutrigenomics have emerged with a focus on the phytochemical nutrient-gene interactions toward cancer prevention in which signaling pathways, networks, and epigenetic phenomena are investigated (Ferguson and Schlothaue, 2012).…”

Basic concepts of epigenetics

“…In other imprinting, 12 histone modifications and the establishment of specific expression profiles of non-coding miRNAs. 13,14 Given the enormous impact of early epigenetic programming and the serious nature of related developmental conditions, such as Praeder-Willi, Angelman and Beckwith-Wiedemann syndromes, neural tube defects, adult onset psychiatric disorders, obesity, cancer and schizophrenia, [15][16][17][18][19] considerable attention is given to the "nurture of the epigenome" prior to birth. A number of community outreach projects such as the CDC's National Center on Birth Defects and Developmental Disabilities promote awareness about reducing the risk of epigenetic related defects such as spina bifida by suggesting an adequate intake of epigenetic-related nutrients (e.g., choline, vitamin B 12 , B 6 and folate) during pregnancy.…”

Epigenetics of Arterial Hypertension

“…Її дефіцит призводить до глобального гіпометилюван-ня ДНК, що є фактором ризику розвитку серцево-судинних захворювань [23]. При Епігенетика артеріальної гіпертензії атеросклерозі ГМК судин трансформуються і набувають низку характерних рис ракових клітин (надлишкова експресія протоонко-генів, факторів росту, а також підвищена рухливість клітин) [23].…”

“…Нутрієнти та вітаміни В6 і В12 регулюють метаболізм гомоцистеїну. Зменшення надходження в організм ЛПНЩ і харчової солі, достатній вміст у їжі фолієвої кислоти або ресвератролу -це ті харчові чинники, які мають велике значення в профі-лактиці серцево-судинних захворювань [23,43]. Фолати разом із метіоніном забезпечу-ють виробництво S-аденозилметіоніну, який є донором вуглецю для метилювання ДНК [44].…”