Annual Meeting of the NCI Cohort Consortium (Abstract Submission): Submission #1

Abstract: Environmental stressors have been shown to alter DNA methylation that can serve as an important step in response to environmental stimuli and the onset of disease. However, little is known about the epigenetic modifications from arsenic exposure, especially in the rural state where cancer incidence and mortality is high. 134 salivary DNA samples were randomly selected from participants in the Arkansas Rural Community Health (ARCH) study where more than 26,000 women from all 75 counties in Arkansas contributed saliva samples and a short baseline questionnaire on breast cancer risk. Arsenic levels were quantified using the inductively coupled plasma mass spectrometry (iCAP RQ ICP-MS). DNA samples were processed and assayed for genome-wide DNA methylation profiles using the Illumina Infinium MethylationEPIC 850K array. R package CpGassoc was used to identify probes that are significantly associated with arsenic levels. Using the relative beta values, we identified the top 100 probes associated with high (top 15%) salivary arsenic concentrations when compared with low (bottom 85%) concentrations among 134 ARCH participants, with 5 genes hypermethylated and 15 genes hypomethylated including the pro-apoptotic gene TP53AIP1. When the participants were stratified by breast cancer diagnosis, arsenic levels were significantly higher among breast cancer patients than healthy participants were. Heavy metals are endocrine disruptors with the ability to induce epigenetic aberration. Here we demonstrated the strong correlation of epigenetic alterations from arsenic exposure. Further study is needed to understand mechanisms underlying those changes to address the environmental exposure and cancer incidence in rural communities, especially on early-onset cancers.