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


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.

SUBMITTER: Muse ME 

PROVIDER: S-EPMC10068446 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Muse Meghan E ME   Carroll Connolly D CD   Salas Lucas A LA   Karagas Margaret R MR   Christensen Brock C BC  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20230401 4


<h4>Background</h4>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 alterat  ...[more]

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