Abstract 842: Racial disparity in breast cancer: Tissue-specific epigenetic mechanisms

Abstract

Abstract Racial disparity in breast cancer is well recognized. Compared with European American (EA) women, African American (AA) women have higher mortality rate despite low incidence rate, and they are more likely being diagnosed at younger age and with features that are more aggressive. Many risk factors of breast cancer, including social, culture, behavioral, genetics, and environmental factors, are disproportionally distributed across two racial groups. These factors could influence DNA methylation differently, as suggested by recent reports that describe biological differences of breast tumor in different racial group. However, no studies have systematically evaluate tissue-specific epigenetic mechanisms underlying the observed racial disparity in breast cancer development. We conducted a molecular epidemiological study of 276 EA and 186 AA healthy women. Genome-wide DNA methylation profiling was performed in normal breast tissue using the Illumina Methyl Captured EPIC-sequencing. Genome-wide association between race and DNA methylation identified differentially methylated sites near genes implicated in metastatic potential and aggressiveness of tumor, tamoxifen-resistance, immune response, and cancer-related metabolic pathways. Many of these genes have not been reported previously to be associated with breast cancer or racial disparities. Further analyses showed that differentially methylated sites across two racial groups were significantly overlapped with differentially methylated sites in tumor and normal breast tissue, suggesting tissue- and racial-specific epigenetic mechanisms underlying breast cancer development. Furthermore, meQTL analyses between known breast cancer risk loci and DNA methylation also suggested AA-specific risk loci were associated with DNA methylation sites implicated in metastatic potential and aggressiveness of tumor. Our study sheds light on tissue-specific genetic and epigenetic mechanisms underlying racial disparity in breast cancer. Further research is warranted to validate the findings in larger studies and to understand gene regulation network by linking with RNA-seq data. Citation Format: Nan Lin, James Castle, Jinpeng Liu, Aditi Shendre, Chi Wang, Yunlong Liu, Chunyan He. Racial disparity in breast cancer: Tissue-specific epigenetic mechanisms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 842.