Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States

Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw P-value < .05 when comparing the 2 ethnic groups, yet were not statistically significant at a 5% false discovery rate (q-value < .05). In the epigenome-wide analysis, 76 loci exhibited DNA methylation differences at q < .05. Among these, 3 CpG sites in the promoter region of the biotransformation gene SULT1C2 had lower methylation in Hispanic compared to non-Hispanic firefighters. Other differentially methylated loci included genes that have been implicated in carcinogenesis in published studies (FOXK2, GYLTL1B, ZBTB16, ARHGEF10, and more). In this pilot study, we report differential DNA methylation between Hispanic and non-Hispanic firefighters in xenobiotic metabolism genes and other genes with functions related to cancer. Epigenetic susceptibility by ethnicity merits further study as this may alter risk for cancers linked to toxic exposures.