ASPO Abstracts
Racial differences in breast tissue-specific epigenetic age
Category: Cancer Health Disparities
Conference Year: 2019
Abstract Body:
Epigenetic age is an indicator of biological aging and tissue specific. Emerging evidence suggests that female breast tissue ages faster than other parts of the body according to epigenetic age estimation using the "Horvath Clock" model. 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. Whether there are differences in biological aging in EA and AA breast tissue remains largely unknown. In addition, the Horvath method is based on the DNA methylation of 353 CpG loci on the outdated Illumina microarray platforms. The increasing availability of next-generation sequencing data calls for method development that uses DNA methylation sequencing data to estimate tissue-specific epigenetic age. We developed a new method to estimate breast tissue-specific epigenetic aging using next-generation methylation sequencing data and assessed the difference between epigenetic and chronological ages, known as epigenetic age acceleration, in 276 EA and 186 AA healthy women. DNA methylation profiles of approximately 3.3 million CpG sites were generated using the Illumina TruSeq Methyl Capture EPIC sequencing technology. Using an elastic net penalized regression model following the Horvath approach, we defined a new set of 247 clock CpGs specific to breast tissue in randomly divided training (n = 370) and testing (n = 92) data sets. We found that breast tissue-specific epigenetic age was positively correlated with chronological age (r=0.87; P<2.2X10-16). Interestingly, AA women showed an increased epigenetic age acceleration compared to EA women (beta=4.6 years, P=0.036). Further research is needed to determine whether epigenetic age acceleration in normal breast tissue is predictive of risks of breast cancer and subtypes.
Keywords: epigenetic ageDNA methylationbreast cancer