American Association for Cancer Research
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Figure S7 from Application of Novel Breast Biospecimen Cell-Type Adjustment Identifies Shared DNA Methylation Alterations in Breast Tissue and Milk with Breast Cancer–Risk Factors

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posted on 2023-04-03, 08:22 authored by Meghan E. Muse, Connolly D. Carroll, Lucas A. Salas, Margaret R. Karagas, Brock C. Christensen

Distribution of the estimated relative proportion of each component cell type in (A) solid breast tissue (n = 95) and (B) breast milk (n = 48) by subject family history of breast cancer. Component cell types include epithelial cells, endothelial cells, fibroblasts, adipocytes, B cells, CD4+ T cells, CD8+ T cells, monocytes, neutrophils, and NK cells. Bonferroni-corrected P values shown from two sample t-tests.


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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. 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 (n = 95) and breast milk (n = 48) samples using genome-scale DNA methylation measures from the Illumina HumanMethylation450 array. We identified 772 hypermethylated CpGs (P < 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 SFRP2, a gene observed to undergo promoter hypermethylation in breast cancer. Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens. 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.

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