Data from Application of Novel Breast Biospecimen Cell-Type Adjustment Identifies Shared DNA Methylation Alterations in Breast Tissue and Milk with Breast Cancer–Risk Factors

Abstract

<div>AbstractBackground:<p>DNA methylation patterning is cell-type–specific and altered DNA methylation is well established to occur early in breast carcinogenesis, affecting non-cancerous, histopathologically normal breast tissue. Previous work assessing risk factor–associated alterations to DNA methylation in breast tissue has been limited, with even less published research in breast milk, a noninvasively obtained biospecimen containing sloughed mammary epithelial cells that may identify early alterations indicative of cancer risk.</p>Methods:<p>Here, we present a novel library for the estimation of the cellular composition of breast tissue and milk and subsequent assessment of cell-type–independent alterations to DNA methylation associated with established breast cancer–risk factors in solid breast tissue (<i>n</i> = 95) and breast milk (<i>n</i> = 48) samples using genome-scale DNA methylation measures from the Illumina HumanMethylation450 array.</p>Results:<p>We identified 772 hypermethylated CpGs (<i>P</i> < 0.01) associated with age consistent between breast tissue and breast milk samples. Age-associated hypermethylated CpG loci were significantly enriched for CpG island shore regions known to be important for regulating gene expression. Among the overlapping hypermethylated loci mapping to genes, a differentially methylated region was identified in the promoter region of <i>SFRP2</i>, a gene observed to undergo promoter hypermethylation in breast cancer.</p>Conclusions:<p>Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens.</p>Impact:<p>This work demonstrates the potential of using breast milk as a noninvasive biomarker of breast cancer risk, improving our ability to detect early-stage disease and lowering the overall disease burden.</p></div>