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Prediagnostic breast milk DNA methylation alterations in women who develop breast cancer

ABSTRACT: Prior candidate gene studies have shown tumor suppressor DNA methylation in breast milk related with history of breast biopsy, an established risk factor for breast cancer. To further establish the utility of breast milk as a tissue-specific biospecimen for investigations of breast carcinogenesis we measured genome-wide DNA methylation in breast milk from women with and without a diagnosis of breast cancer in two independent cohorts. In epigenome-wide analyses we identified 58 differentially methylated CpG sites associated with breast cancer diagnosis in the prospectively collected milk samples from the breast that would develop cancer compared with women without a diagnosis of breast cancer (q-value < 0.05), using linear mixed effects models adjusted for history of breast biopsy, age, age of the baby, cell type proportion estimates, array chip, and subject as random effect. Nearly all sites associated with breast cancer diagnosis were hypomethylated in cases compared with controls, and CpG sites were enriched for CpG islands. In addition, inferred repeat element methylation was lower in breast milk DNA from cases compared to controls, and cases exhibited increased estimated epigenetic mitotic tick rate as well as DNA methylation age compared with controls. Breast milk has promise as a biospecimen for prospective assessment of disease risk, and for understanding the underlying molecular basis of breast cancer risk factors and improving primary and secondary prevention of breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133918 | GEO | 2019/12/06

REPOSITORIES: GEO

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