Genomic Methylation Changes Over Time in Peripheral Blood Mononuclear Cell DNA: Differences by Assay Type and Baseline Values

Abstract

Lower levels of genomic DNA methylation in blood DNA has been associated with risk of different cancers and several cancer risk factors. To understand the use of genomic methylation measures as biomarkers of cancer risk, data are needed on within-individual changes over time. Using information from 77 subjects with blood collected at 2 visits on average 8 years apart, we examined whether levels of DNA methylation change with time and if so, whether selected cancer risk factors predict these changes. We measured DNA methylation levels in peripheral blood mononuclear cells (PBMC) using three assays that have been used in epidemiologic studies: (i) luminometric methylation assay (LUMA)(ii) LINE-1 by pyrosequencing, and (iii) Sat2 by MethyLight. Close to a third of all individuals had large changes over time (≥10%) in LUMA with 19.5% increasing and 13.0% decreasing. For Sat2, two-thirds of individuals had large changes with 40% increasing and 26% decreasing over time. In contrast, only 3.9% of individuals had large changes in LINE-1 over time. The degree of change in PBMC DNA methylation was statistically significantly inversely associated with methylation levels at baseline; greater decreases were observed in individuals with higher baseline values for each assay. These data, if replicated, suggest that changes in DNA methylation over time are highly associated with baseline values of the assay and vary by assay type. These findings suggest that assays that change more over time may warrant consideration for studies that measure later life exposures.