Abstract C062: Racial differences in genome-wide DNA methylation profiles by county poverty levels among women residing in Arkansas

Abstract

Abstract Introduction and Purpose: DNA methylation is a potential biomarker of cellular stress and biologic aging, above that of chronologic age. Aberrant DNA methylation patterns have been associated with overall health and life expectancies and can be susceptible to biologic and environmental influences and stressors. DNA methylation has been shown to be modified by adverse living conditions in urban neighborhoods, but there is little knowledge of how adverse rural environments impact these biomarkers. An algorithm has been developed and validated that quantifies epigenetic age, and this measure has been strongly associated with health and life expectancy but has not been explored in rural and rural minority populations who have documented overall health disparities. The goal of this pilot study is to examine the impact of adverse rural neighborhoods on biomarkers of DNA methylation and epigenetic aging. Methods: Genome-wide DNA methylation was assessed using the Illumina 850K EPIC Beadchip, and the DNA methylation age estimation was derived using the algorithms Horvath developed based on the DNA methylation levels. Percent poverty rate at the census level was obtained according to their zip code data by ArcGIS. Ten women of self-reported African American (AA) descent each from counties with high poverty rates (>20% of the population) and those with low poverty rates (<10%) were randomly selected based on the 2008-2012 US Census American Community Survey, as well as ten women each of European American (EA) descent from counties with high or low poverty rates. Ingenuity Pathway Analysis (IPA) was performed to identify biologic pathways that were differentially methylated between residents of counties with high or low poverty rates and by race. Results: Among AA women, hypermethylation was more common in AA residents of counties with low compared to high poverty rates (70% vs 30%). The top canonical pathways impacted by differential methylation were related to glucocorticoid receptor, p53, and estrogen-dependent breast cancer signaling in AA women. EA women living in low-poverty counties exhibited less hypermethylation of CpGs than those living in high-poverty counties (27% vs. 73%). The top canonical pathways were related to hereditary breast cancer, glucocorticoid receptor, androgen and PI3K/AKT signaling. Epigenetic age of the 39 women in the study was highly correlated with their chronologic age (r=0.82, p=1.71e-10). When epigenetic age acceleration was considered, however, no significant differences by race and/or poverty levels were apparent. Conclusions: The finding of this pilot study suggests that living in adverse neighborhoods may impact DNA methylation patterns in breast cancer-related pathways when compared to living in affluent ones, and the pattern appears to be different on race. Larger studies should confirm our findings. Citation Format: Ping-Ching Hsu, Susan Kadlubar, Daniel Acheampong, Lora Rogers, Gail Runnells, Pearl McElfish, Mario Schootman, L. Joseph Su. Racial differences in genome-wide DNA methylation profiles by county poverty levels among women residing in Arkansas [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C062.