Abstract IA16: Identifying an epigenetic basis for arsenic-associated bladder cancer in a population in Chihuahua Mexico

Abstract

Epidemiologic evidence links chronic exposure to inorganic arsenic (iAs) to a host of adverse health effects, including cancer of the bladder. This study aimed to identify DNA methylation patterns associated with arsenic and its metabolites in exfoliated urothelial cells (EUCs) that originate primarily from the urinary bladder, one of the targets of arsenic-induced carcinogenesis. EUCs from 46 residents of Chihuahua, Mexico were analyzed for genome-wide, gene-specific promoter DNA methylation levels. These were analyzed in relation to intracellular concentrations of total arsenic and arsenic species. A set of 49 differentially methylated genes was identified with increased promoter methylation associated with EUC tAs, iAs, and/or monomethylated As (MMAs) enriched for their roles in metabolic disease and cancer. Notably, no genes had differential methylation associated with EUC dimethylated As (DMAs), suggesting that DMAs may influence DNA methylation-mediated urothelial cell responses to a lesser extent than iAs or MMAs. Further analysis showed that 22 of the 49 arsenic-associated genes (45%) are also differentially methylated in bladder cancer tissue identified using The Cancer Genome Atlas (TCGA) repository. Both the arsenic- and cancer-associated genes were enriched for the binding sites of common transcription factors known to play roles in carcinogenesis, demonstrating a novel potential mechanistic link between iAs exposure and bladder cancer. Citation Format: Rebecca C. Fry, Rebecca C. Fry. Identifying an epigenetic basis for arsenic-associated bladder cancer in a population in Chihuahua Mexico [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr IA16.