Induction of epigenetic alterations by dietary and other environmental factors.
ABSTRACT 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.
SourceAvailable from: Daniel Levy[Show abstract] [Hide abstract]
ABSTRACT: Background DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age. Results Here we test whether differences between people’s chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43. Conclusions DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0584-6) contains supplementary material, which is available to authorized users.Genome Biology 01/2015; 16(1):25. DOI:10.1186/s13059-015-0584-6 · 10.47 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Chronic liver injury can lead to the development of liver fibrosis and cirrhosis but only in a minority of patients. Currently, it is not clear which factors determine progression to fibrosis. We investigated whether DNA\methylation profile as determined by pyrosequencing can distinguish patients with mild from those with advanced/severe fibrosis in non-alcoholic liver disease (NAFLD) and alcoholic liver disease (ALD). To this end, paraffin-embedded liver biopsies were collected from patients with biopsy-proven NAFLD or ALD, as well as paraffin-embedded normal liver resections, genomic DNA isolated, bisulfite converted and pyrosequencing assays used to quantify DNA methylation at specific CpGs within PPARα, PPARα, TGFβ1, Collagen 1A1 and PDGFα genes. Furthermore, we assessed the impact of age, gender and anatomical location within the liver on patterns of DNA methylation in the same panel of genes. DNA methylation at specific CpGs within genes known to affect fibrogenesis distinguishes between patients with mild from those with severe fibrosis in both NAFLD and ALD, although same CpGs are not equally represented in both etiologies. In normal liver, age, gender or anatomical location had no significant impact on DNA methylation patterns in the liver. DNA methylation status at specific CpGs may be useful as part of a wider set of patient data for predicting progression to liver fibrosis.03/2015; 7(1):25. DOI:10.1186/s13148-015-0056-6
[Show abstract] [Hide abstract]
ABSTRACT: Epigenetic mechanisms play a pivotal role in the expression of genes and can be influenced by both the quality and quantity of diet. Dietary compounds such as sulforaphane (SFN) found in cruciferous vegetables and epigallocatechin-3-gallate (EGCG) in green tea exhibit the ability to affect various epigenetic mechanisms such as DNA methyltransferase (DNMT) inhibition, histone modifications via histone deacetylase (HDAC), histone acetyltransferase (HAT) inhibition, or noncoding RNA expression. Regulation of these epigenetic mechanisms has been shown to have notable influences on the formation and progression of various neoplasms. We have shown that an epigenetic diet can influence both cellular longevity and carcinogenesis through the modulation of certain key genes that encode telomerase and p16. Caloric restriction (CR) can also play a crucial role in aging and cancer. Reductions in caloric intake have been shown to increase both the life- and health-span in a variety of animal models. Moreover, restriction of glucose has been demonstrated to decrease the incidence of age-related diseases such as cancer and diabetes. A diet rich in compounds such as genistein, SFN and EGCG can positively modulate the epigenome and lead to many health benefits. Also, reducing the quantity of calories and glucose in the diet can confer an increased health-span, including reduced cancer incidence. © 2015. Published by The Company of Biologists Ltd.Journal of Experimental Biology 01/2015; 218(Pt 1):59-70. DOI:10.1242/jeb.107110 · 3.00 Impact Factor