Application of Novel Breast Biospecimen Cell-Type Adjustment Identifies Shared DNA Methylation Alterations in Breast Tissue and Milk with Breast Cancer–Risk Factors
Year: 2023
Type: article
Study design: Observational Study
Abstract: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens. IMPACT: 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.
Institutions: Dartmouth College, Dartmouth Health
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: U.S. Department of Defense, U.S. Environmental Protection Agency, Dartmouth College, Wellcome Trust, National Institutes of Health, NIH Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences, Congressionally Directed Medical Research Programs
Awards: EPIGENETIC MODIFICATIONS OF CYTOSINES IN CLEAR CELL KIDNEY CARCINOGENESIS AND SURVIVAL, Center for Molecular Epidemiology, Epigenetic Modifications of Cytosines in Clear Cell Kidney Carcinogenesis and Survival, Children's Environmental Health & Disease Prevention Research Center at Dartmouth, (PQ3) Immune epigenetic biomarkers of bladder cancer outcomes, G4119534169, Training Program for Quantitative Population Sciences in Cancer, G766807502, G862384199, G9000082517, Cancer Center Support Grant, DNA-based Immune Phenotyping in HNSCC for Biomarkers of Response to Immunotherapy
OpenAlex ID: W4320486105