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Enhanced exposure assessment and genome-wide DNA methylation in World Trade Center disaster responders

Kuan, Pei-Fena; Mi, Zhongyuand; Georgopoulos, Panosd; Hashim, Danac; Luft, Benjamin J.b; Boffetta, Paoloc

European Journal of Cancer Prevention: May 2019 - Volume 28 - Issue 3 - p 225–233
doi: 10.1097/CEJ.0000000000000460
Research Papers: Carcinogenesis

DNA methylation has emerged as a promising target linking environmental exposures and cancer. The World Trade Center (WTC) responders sustained exposures to potential carcinogens, resulting in an increased risk of cancer. Previous studies of cancer risk in WTC-exposed responders were limited by the deficiency in quantitative and individual information on exposure to carcinogens. The current study introduces a new exposure-ranking index (ERI) for estimating cancer-related acute and chronic exposures, which aimed to improve the ability of future analyses to estimate cancer risk. An epigenome-wide association study based on DNA methylation and a weighted gene co-expression network analysis were carried out to identify cytosine-phosphate-guanosine (CpG) sites, modules of correlated CpG sites, and biological pathways associated with the new ERI. Methylation was profiled on blood samples using Illumina 450K Beadchip. No significant epigenome-wide association was found for ERI at a false discovery rate of 0.05. Several cancer-related pathways emerged in pathway analyses for the top ranking genes from epigenome-wide association study as well as enriched module from the weighted gene co-expression network analysis. The current study was the first DNA methylation study that aimed to identify methylation signature for cancer-related exposure in the WTC population. No CpG sites survived multiple testings adjustment. However, enriched gene sets involved in cancer, were identified in both acute and chronic ERIs, supporting the view that multiple genes play a role in this complex exposure.

aDepartment of Applied Mathematics and Statistics

bDepartment of Medicine, Stony Brook University, Stony Brook

cTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, New York

dEnvironmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA

Correspondence to Paolo Boffetta, MD, MPH, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1130, New York NY 10029, USA Tel: +1 212 824 7378; fax: +1 212 849 2566; e-mail:

Received November 5, 2017

Accepted June 7, 2018

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