ASPO Abstracts
Potential DNA methylation markers for breast cancer development
Category: Molecular Epidemiology & Environment
Conference Year: 2020
Abstract Body:
DNA methylation plays a key role in breast cancer development. Abnormal DNA methylation
contributes to genomic instability and leads to gene dysregulation. Changes in DNA
methylation are tissue-specific and are influenced by both environmental and genetic
factors. However, it remains a challenge to identify tissue-specific DNA methylation markers
for breast cancer development prospectively. We hypothesized that DNA methylation
changes that drive breast cancer development occurs in normal breast tissue before cancer
diagnosis, and such changes were correlated with the time interval to diagnosis. In this
study, we compared genome-wide DNA methylation profiles of normal breast tissue
between women who developed breast cancer within 7 years of tissue donation (cases) and
women who remained no breast cancer with at least same length of follow-up (controls).
Cases and controls were matched on exact age at tissue donation. Out of the 3.3M CpGs
tested, we identified approximately 29K and 16K CpGs that were differentially methylated
(|∆β|>0.10, P<0.05) between cases and controls for women of European Americans (EA)
and African Americans (AA), respectively, and 1002 and 820 of those CpGs whose ∆β were
also highly correlated with the time interval between age at donation and age at diagnosis
among cases (|r|>0.9, P<0.05). Further gene annotation and pathway analyses suggested
these CpG sites were enriched in inflammation response for both EA and AA women, but
enriched in cell differentiation and lipid metabolism for EA women and in angiogenesis for
AA women. Our study identified potential DNA methylation markers that drives breast
cancer development. Further research is needed to validate these results in larger samples.
Keywords: DNA Methylation Breast Cancer Racial differences pathways