Human exposure to trichloroethylene is associated with increased variability of blood DNA methylation that is enriched in genes and pathways related to autoimmune disease and cancer

Rachael V Phillips*, Linda Rieswijk, Alan E Hubbard, Roel Vermeulen, Jinming Zhang, Wei Hu, Laiyu Li, Bryan A Bassig, Jason Y Y Wong, Boris Reiss, Yongshun Huang, Cuiju Wen, Mark Purdue, Xiaojiang Tang, Luoping Zhang, Martyn T Smith, Nathaniel Rothman, Qing Lan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Human exposure to trichloroethylene (TCE) is linked to kidney cancer, autoimmune diseases, and probably non-Hodgkin lymphoma. Additionally, TCE exposed mice and cell cultures show altered DNA methylation. To evaluate associations between TCE exposure and DNA methylation in humans, we conducted an epigenome-wide association study (EWAS) in TCE exposed workers using the HumanMethylation450 BeadChip. Across individual CpG probes, genomic regions, and globally (i.e., the 450K methylome), we investigated differences in mean DNA methylation and differences in variability of DNA methylation between 73 control (< 0.005 ppm TCE), 30 lower exposed (< 10 ppm TCE), and 37 higher exposed ( ≥ 10 ppm TCE) subjects' white blood cells. We found that TCE exposure increased methylation variation globally (Kruskal-Wallis p-value = 3.75e-3) and in 25 CpG sites at a genome-wide significance level (Bonferroni p-value < 0.05). We identified a 609 basepair region in the TRIM68 gene promoter that exhibited hypomethylation with increased exposure to TCE (FWER = 1.20e-2). Also, genes that matched to differentially variable CpGs were enriched in the 'focal adhesion' biological pathway (p-value = 2.80e-2). All in all, human exposure to TCE was associated with epigenetic alterations in genes involved in cell-matrix adhesions and interferon subtype expression, which are important in the development of autoimmune diseases; and in genes related to cancer development. These results suggest that DNA methylation may play a role in the pathogenesis of TCE exposure-related diseases and that TCE exposure may contribute to epigenetic drift.

Original languageEnglish
Pages (from-to)1112-1124
Number of pages13
Issue number11
Early online date26 Jun 2019
Publication statusPublished - 2 Nov 2019


  • DNA methylation
  • TCE
  • autoimmune disease
  • epigenetic variability
  • epigenetics
  • epigenome-wide association study (EWAS)
  • occupational exposure

Cite this