Global Methylation in Exposure Biology and Translational Medical Science

BACKGROUND Many groups are actively investigating how the epigenetic state relates to environmental exposures and development of disease, including cancer. There are myriad choices for capturing and measuring the epigenetic state of a tissue, ranging from assessing the total methyl-CpG content to array-based platforms that simultaneously probe hundreds of thousands of CpG loci. There is an emerging literature that uses CpG methylation at repetitive sequences, including LINE-1 (long interspersed nuclear element-1) elements, to capture the epigenomic state. OBJECTIVES We explored the complexity of using CpG methylation at repetitive sequences in epidemiology and translational medical research and suggest needed avenues of research to clarify its meaning and utility. CONCLUSIONS Among the most urgent avenues of research is the need for prospective studies to eliminate the possibilities of reverse causality, and development of new LINE-1 assays that capture both class of LINE-1 element and copy number.