Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence

Abstract

Current evidence supports the notion that environmental exposures are associated with DNA-methylation and expression changes that can impact human health. Our objective was to conduct a systematic review of epidemiologic studies evaluating the association between environmental chemicals with DNA methylation levels in adults. After excluding arsenic, recently evaluated in a systematic review, we identified a total of 17 articles (6 on cadmium, 4 on lead, 2 on mercury, 1 on nickel, 1 on antimony, 1 on tungsten, 5 on persistent organic pollutants and perfluorinated compounds, 1 on bisphenol A, and 3 on polycyclic aromatic hydrocarbons). The selected articles reported quantitative methods to determine DNA methylation including immunocolorimetric assays for total content of genomic DNA methylation, and microarray technologies, methylation-specific quantitative PCR, Luminometric Methylation Assay (LUMA), and bisulfite pyrosequencing for DNA methylation content of genomic sites such as gene promoters, LINE-1, Alu elements, and others. Considering consistency, temporality, strength, dose-response relationship, and biological plausibility, we concluded that the current evidence is not sufficient to provide inference because differences across studies and limited samples sizes make it difficult to compare across studies and to evaluate sources of heterogeneity. Important questions for future research include the need for larger and longitudinal studies, the validation of findings, and the systematic evaluation of the dose-response relationships. Future studies should also consider the evaluation of epigenetic marks recently in the research spotlight such as DNA hydroxymethylation and the role of underlying genetic variants.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0055-7) contains supplementary material, which is available to authorized users.

Ecotoxic pharmaceuticals, personal care products, and other emerging contaminants: A review of environmental, receptor-mediated, developmental, and epigenetic toxicity with discussion of proposed toxicity to humans

“…Despite limited epigenetics study regarding DNA methylation, Ruiz-Hernandez et al (2015) conclude that DNA will generally tend towards hypomethylation (potentially opening promoter regions to transcription machinery) with increasing contaminant exposure levels. However, exceptions to this trend exist.…”

“…Endocrine disruption in humans has been suggested and effects in lower organisms offer additional insight into possible human toxicity although effects on humans are highly debated (see Section 5) (Teeguarden et al 2013;Fisher et al, 2014;Prins et al 2014;Ruiz-Hernandez et al 2015). The full study of environmental and aquatic EDCs will not be discussed here and is specifically reviewed in greater scope and detail elsewhere (Patisaul and Adewale 2009;Fisher et al 2014).…”

“…However, environmental epigenetics and possible effects on humans is of increasing research interest and likely a subject that will dominate future toxicological study. Several reviews can be found incorporating discussion of potential links to humans in greater detail than here including with regard to endocrine disease (Fleisch et al 2012), gonadal effects and female reproduction (Uzumcu et al 2012), and DNA methylation in adults (Ruiz-Hernandez et al 2015).…”

“…Endocrine disrupting compounds have been hypothesised to affect human gene regulation via epigenetic mechanisms (Fleisch et al 2012;Rissman and Adli 2014;LaRocca et al 2015;Ruiz-Hernandez et al 2015). Despite limited epigenetics study regarding DNA methylation, Ruiz-Hernandez et al (2015) conclude that DNA will generally tend towards hypomethylation (potentially opening promoter regions to transcription machinery) with increasing contaminant exposure levels.…”

“…Numerous reviews have examined primary study of exposure to chemicals in the environment and the incidence of obesity La Merril and Brinbaum 2011;vom Saal et al 2012;Thayer et al 2012;Jeon et al 2015), type 2 diabetes mellitus (T2DM) Jeon et al 2015), breast cancer (Soto and Sonnenschein 2015), DNA methylation alterations in adults (Ruiz-Hernandez et al 2015), advancement of puberty Fisher and Eugster 2014), poor semen quality/viability (Li et al 2011), and various disruptions to childhood development (Meeker 2012). Conducting a comprehensive preliminary review of primary research in humans linking prenatal or early childhood exposure (up to 8 years of age) to environmental chemicals (other than tobacco smoke, alcohol, recreational drugs and pharmaceutical compounds) and susceptibility to disease/dysfunction across the human lifespan, Heindel et al (2015) found 283 publications reporting a significant correlation between exposure and disease/dysfunction and 60 reporting non-significant associations.…”