Kuan PF, et al. - This investigation represents the first attempt to discover DNA methylation signature for cancer-related exposure in the World Trade Center (WTC) population as DNA methylation has emerged as a promising target linking environmental exposures and cancer and WTC responders carry an increased risk of developing cancer. To ensure an improved estimation of cancer risk in future analyses, researchers proposed a new exposure-ranking index (ERI) that helps to evaluate cancer-related acute and chronic exposures. To detect cytosine-phosphate-guanosine (CpG) sites, modules of correlated CpG sites, and biological pathways related to the new ERI, they performed an epigenome-wide association study based on DNA methylation and a weighted gene co-expression network analysis. Using Illumina 450K Beadchip, they profiled methylation on blood samples. At a false discovery rate of 0.05, no significant epigenome-wide link was found for ERI. They identified various cancer-related pathways. No CpG sites survived multiple testings adjustment. In both acute and chronic ERIs, enriched gene sets involved in cancer were found, implying the involvement of multiple genes in this complex exposure.