title: 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.
authors.affiliation: Department of Internal Medicine, Hospital Clínico de Valencia, Avenida Blasco Ibañez, 17, 46010 Valencia, Spain ; Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic de Valencia INCLIVA, Av. Menendez Pelayo 4, Accesorio, 46010 Valencia, Spain.
authors.forename: Adrian
authors.initials: A
authors.lastname: Ruiz-Hernandez
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA ; Department of Internal Medicine, Kidney Institute and Division of Nephrology, China Medical University Hospital and College of Medicine, China Medical University, 2 Yude Road, Taichung, 40447 Taiwan.
authors.forename: Chin-Chi
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Genotyping and Genetic Diagnosis Unit, Institute for Biomedical Research INCLIVA, Av. Menendez Pelayo, 4 Accesorio, 46010 Valencia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Rentero-Garrido
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA.
authors.forename: Wan-Yee
authors.initials: WY
authors.lastname: Tang
authors.affiliation: Department of Internal Medicine, Hospital Clínico de Valencia, Avenida Blasco Ibañez, 17, 46010 Valencia, Spain ; Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic de Valencia INCLIVA, Av. Menendez Pelayo 4, Accesorio, 46010 Valencia, Spain ; CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Minister of Health, Madrid, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Redon
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111-1524 USA ; Instituto Madrileño de Estudios Avanzados en Alimentación, Ctra. de Cantoblanco 8, 28049 Madrid, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA ; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, 2024 E. Monument Street, Baltimore, 21205 MD USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Navas-Acien
authors.affiliation: Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic de Valencia INCLIVA, Av. Menendez Pelayo 4, Accesorio, 46010 Valencia, Spain ; Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Tellez-Plaza
keywords: Bisphenol A; Cadmium; DNA methylation; Environmental chemicals; Lead; Mercury; Metals; Persistent organic pollutants; Polycyclic aromatic hydrocarbons; Systematic review