Abstract PS7-54: Racial differences in age-related DNA methylation changes in normal breast tissue

Age is a well-established risk factor for breast cancer development. While age-related epigenetic changes are believed to contribute to overall breast cancer risk, the underlying molecular mechanisms are poorly understood. In addition, racial disparity in breast cancer is well recognized. Compared to European American (EA) women, African American (AA) women are more often diagnosed with breast cancer at younger ages, have a more advanced or aggressive disease, and have poorer outcomes. We hypothesize that age-related DNA methylation (DNAm) may contribute to breast cancer risk differently for distinct racial groups. We investigated epigenome-wide age-related DNAm in normal breast tissue from 178 EA and 272 AA women separately using the Illumina TruSeq Methyl Capture EPIC library and NGS technology. We identified 3,944 and 506 CpG loci that were significantly associated with chronological age, of which 3,534 and 504 CpGs were increasingly hypermethylated with older ages and 410 and 2 loci were increasingly hypomethylated with older ages, in EA and AA women, respectively. Despite the different number, all 506 loci that were significantly associated with age in AA women were also significant for EA women. The low number age-related DNAm loci identified in AA women may reflect a more complex interplay of factors on epigenetic mechanisms in this racial group. Pathway analyses suggested these age-related loci are enriched in biological processes including cell communication, signaling, proliferation, and adhesion. We further examined 181 CpG loci that were previously reported to be associated with age in normal breast tissue but found that only six loci were replicated in our dataset. Our results suggested age-related biological pathways that potentially implicated in breast cancer development and a more complex epigenetic mechanisms in AA women. Citation Format: Chunyan He, James Castle, Nan Lin, Yunlong Liu, Chi Wang. Racial differences in age-related DNA methylation changes in normal breast tissue [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-54.