Induction of Epigenetic Alterations by Dietary and Other Environmental Factors

Human Nutrition Research Centre, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom.
Advances in genetics (Impact Factor: 6.76). 12/2010; 71:3-39. DOI: 10.1016/B978-0-12-380864-6.00001-8
Source: PubMed


Dietary and other environmental factors induce epigenetic alterations which may have important consequences for cancer development. This chapter summarizes current knowledge of the impact of dietary, lifestyle, and environmental determinants of cancer risk and proposes that effects of these exposures might be mediated, at least in part, via epigenetic mechanisms. Evidence is presented to support the hypothesis that all recognized epigenetic marks (including DNA methylation, histone modification, and microRNA (miRNA) expression) are influenced by environmental exposures, including diet, tobacco, alcohol, physical activity, stress, environmental carcinogens, genetic factors, and infectious agents which play important roles in the etiology of cancer. Some of these epigenetic modifications change the expression of tumor suppressor genes and oncogenes and, therefore, may be causal for tumorigenesis. Further work is required to understand the mechanisms through which specific environmental factors produce epigenetic changes and to identify those changes which are likely to be causal in the pathogenesis of cancer and those which are secondary, or bystander, effects. Given the plasticity of epigenetic marks in response to cancer-related exposures, such epigenetic marks are attractive candidates for the development of surrogate endpoints which could be used in dietary or lifestyle intervention studies for cancer prevention. Future research should focus on identifying epigenetic marks which are (i) validated as biomarkers for the cancer under study; (ii) readily measured in easily accessible tissues, for example, blood, buccal cells, or stool; and (iii) altered in response to dietary or lifestyle interventions for which there is convincing evidence for a relationship with cancer risk.

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    • "The risks associated with white rice consumption based on the findings so far suggest that less consumption of white rice may be helpful towards reducing risk of cardiometabolic diseases, especially Type 2 diabetes. Furthermore, epigenetic studies have demonstrated that dietary factors and habits can induce intrauterine molecular reprogramming events in growing fetuses with consequent increase in the risk of chronic diseases (Mathers et al., 2009; Skinner et al., 2010). Hence, it is likely also that epigenetic events due to excessive white rice consumption are promoting the transgenerational risk of cardiometabolic diseases. "
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    ABSTRACT: White rice is a major staple food for people in low to middle income countries and it can increase the risk of cardiometabolic disease. Brown rice, especially when germinated, is a healthier alternative. Various functional properties have been documented for the bioactive-rich germinated brown rice. Nutrigenomic studies, dwelling on interactions at diet-genome interface, have expanded our understanding of the role of diets on health. The nutrigenomic basis for the functional properties of GBR have also been reported; its antihyperglycemic, hypocholesterolemic, and antioxidative effects are mediated by its bioactives, partly via transcriptional regulation of genes involved in gluconeogenesis, cholesterol metabolism, and oxidative stress, respectively. Additionally, GBR's ability to improve menopausal symptoms is reported to be due to its ability to upregulate bone metabolism and uterine estrogen related genes, and downregulate inflammatory genes. Food synergy plays a role in the overall functional effects of GBR. Further studies on proteomics, metabolomics, nutrikinetics, and nutridynamics are indicated.
    Genomics, Proteomics and Metabolomics in Nutraceuticals and Functional Foods, Second Edition edited by Debasis Bagchi, Anand Swaroop, Manashi Bagchi, 08/2015: chapter 39; John Wiley & Sons, Ltd, Chichester, UK., ISBN: 9781118930458
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    • "diet, life style, air pollution and heavy metals) can change the methylation status of gene promoters, modify gene expression and ultimately modify cellular function [reviewed by [4] [10]]. In addition , early life exposures have been reported to produce aberrant patterns of epigenetic marks that are sustained across the lifecourse and result in down-regulation of cell defence mechanisms [4] [10] [11] possibly via epigenetic mechanisms including altered DNA methylation. DNA methylation is an epigenetic modification of the genome that may result in changes in gene expression and phenotype without altering the DNA sequence, thus introducing a process of genome regulation. "
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    ABSTRACT: Oxidative stress via redox reactions can regulate DNA repair pathways. The base excision repair (BER) enzyme apurinic/apyrimidinic endonuclease 1 (APE1) is a key player in the redox regulation of DNA repair. Environmental factors can alter the methylation of DNA repair genes, change their expression and thus modulate BER activity and susceptibility to oxidative DNA damage. Therefore, we hypothesized that epigenetic modifications play a role in the redox regulation of APE1 in hippocampi of newborns and investigated the effect of supplementation of pregnant sows with a diet enriched in antioxidants and other nutrients on oxidative stress, DNA methylation and DNA repair in their offspring. High levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and low levels of glutathione were detected in control piglets after birth compared with supplemented piglets, indicating the presence of oxidative stress. In control animals, this oxidative stress was associated with genomic DNA demethylation, decreased APE1 promoter methylation, increased APE1 expression and with slightly but not statistically significant increased BER-related DNA incision activity. Supplementation of piglets with antioxidants and other nutrients significantly lowered 8-oxodG levels compared to control animals, which was accompanied by overall lower APE1 promoter methylation and enhanced APE1 expression at day 7-28 after birth in supplemented piglets, although DNA incision activity was not significantly different between groups. Preliminary attempts to study the interaction between redox and epigenetic regulatory mechanisms revealed an inverse correlation between APE1 expression and methylation of CpG-sites 11 and 13 in the promoter region, which according to Genomatix "MatInspector" are located in the core binding sites of redox-sensitive transcription factors. We are the first to study methylation of the APE1 promoter and its role in mediating the functional effects of redox reactions induced by oxidative stress. Epigenetic and redox mechanisms may interact in regulating APE1-related DNA repair processes, involving redox-sensitive TFs.
    DNA repair 04/2014; 18(1). DOI:10.1016/j.dnarep.2014.03.011 · 3.11 Impact Factor
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    • "The association with the epigenetic status was highest in the most socio-economically deprived group of individuals and lowest in the least deprived group (McGuinness et al., 2012). The epigenetic status (DNA-methylation patterns) was also affected by dietary factors, even during embryogenesis, with further consequences in adult life (Mathers et al., 2010; Thompson et al., 2010; Thornburg et al., 2010). Similarly, the UTS Type-II families living under extremely low socio-economic conditions may also have been subjected to epigenetic changes during embryogenesis (see also Tan, 2010; Tan et al., 2012; Karaca et al., 2013). "
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    ABSTRACT: Two consanguineous families with Uner Tan Syndrome (UTS) were analyzed in relation to self-organizing processes in complex systems, and the evolutionary emergence of human bipedalism. The cases had the key symptoms of previously reported cases of UTS, such as quadrupedalism, mental retardation, and dysarthric or no speech, but the new cases also exhibited infantile hypotonia and are designated UTS Type-II. There were 10 siblings in Branch I and 12 siblings in Branch II. Of these, there were seven cases exhibiting habitual quadrupedal locomotion (QL): four deceased and three living. The infantile hypotonia in the surviving cases gradually disappeared over a period of years, so that they could sit by about 10 years, crawl on hands and knees by about 12 years. They began walking on all fours around 14 years, habitually using QL. Neurological examinations showed normal tonus in their arms and legs, no Babinski sign, brisk tendon reflexes especially in the legs, and mild tremor. The patients could not walk in a straight line, but (except in one case) could stand up and maintain upright posture with truncal ataxia. Cerebello-vermial hypoplasia and mild gyral simplification were noted in their MRIs. The results of the genetic analysis were inconclusive: no genetic code could be identified as the triggering factor for the syndrome in these families. Instead, the extremely low socio-economic status of the patients was thought to play a role in the emergence of UTS, possibly by epigenetically changing the brain structure and function, with a consequent selection of ancestral neural networks for QL during locomotor development. It was suggested that UTS may be regarded as one of the unpredictable outcomes of self-organization within a complex system. It was also noted that the prominent feature of this syndrome, the diagonal-sequence habitual QL, generated an interference between ipsilateral hands and feet, as in non-human primates. It was suggested that this may have been
    Frontiers in Neuroscience 04/2014; 8(8):84. DOI:10.3389/fnins.2014.00084 · 3.66 Impact Factor
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