Abstract 5313: Occupational exposure to trichloroethylene and DNA methylation: a cross-sectional study

Abstract

Abstract Trichloroethylene (TCE) is a chlorinated solvent that is often used in occupational settings for vapor degreasing of metal parts. In 2012, TCE was classified as a known human carcinogen (Group 1) by the International Agency for Research on Cancer, largely based on evidence for kidney cancer. Animal studies have suggested that TCE may modulate DNA methylation. We performed a cross-sectional study to examine the associations of DNA methylation of individual CpG sites with TCE exposure. We enrolled 80 workers from factories where TCE was used, as well as 96 unexposed controls from food and clothes manufacturing factories in the same region, and 69 exposed workers and 77 controls were available for analyses in this study. Personal exposure measurements (2-3 per subject) were collected for a full work shift using a 3MTM badge in both exposed workers and a subgroup of the control workers. Blood samples were collected from each subject and CpG methylation was assayed on the Illumina Infinium HumanMethylation450 BeadChip. After quality controls procedures, 485,512 CpG probes were available for analyses. We used separate multivariable linear regression models to examine the associations of TCE exposure and the methylation level at each single CpG site. All models were adjusted for age, sex, current smoking status, current alcohol consumption, recent infection, and body mass index. The median TCE exposure level in exposed subjects was 12 ppm (10th percentile: 2 ppm; 90th percentile: 45 ppm). We found 29 CpG probes that achieved genome-wide significance (p < 1.04x10-7) when comparing TCE exposed workers with controls. TCE exposure was associated with hypomethylation at nearly all (28/29) of those CpG probes. Of these 29 CpG probes, 6 CpGs showed a significant (p < 1.04x10-7) exposure-response relationship across the categories of controls and lower- (<12ppm) and higher-exposed (≥12 ppm) workers, and were mapped to 6 different chromosomes. To our knowledge, this is the first report that TCE exposure is associated with alterations in DNA methylation in a molecular epidemiologic study. Our findings may provide insight into potential biological mechanisms linking exposure to TCE and adverse health outcomes. Citation Format: Jinming Zhang, Luoping Zhang, Roel Vermeulen, Wei Hu, Bryan A. Bassig, Jason Y. Wong, Min Shen, Bu-Tian Ji, Boris Reiss, Mark Purdue, Martyn T. Smith, Qing Lan, Nathaniel Rothman. Occupational exposure to trichloroethylene and DNA methylation: a cross-sectional study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5313.