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Table S9 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, 08:21 authored by Meghan E. Muse, Connolly D. Carroll, Lucas A. Salas, Margaret R. Karagas, Brock C. Christensen

Shared hypomethylated loci with (P < 0.01) in solid breast tissue and breast milk parity

Funding

National Institute of General Medical Sciences (NIGMS)

United States Department of Health and Human Services

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National Cancer Institute (NCI)

United States Department of Health and Human Services

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National Institute of Environmental Health Sciences (NIEHS)

United States Department of Health and Human Services

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U.S. Environmental Protection Agency (EPA)

U.S. Department of Defense (DOD)

NIH Office of the Director (OD)

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ARTICLE ABSTRACT

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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    Cancer Epidemiology, Biomarkers & Prevention

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