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Epigenetics. 2014 Feb;9(2):268-75. doi: 10.4161/epi.27015. Epub 2013 Nov 6.

Age-related DNA methylation in normal breast tissue and its relationship with invasive breast tumor methylation.

Author information

1
Department of Community and Family Medicine; Section of Biostatistics and Epidemiology; Geisel School of Medicine at Dartmouth; Hanover, NH USA; Department of Pharmacology and Toxicology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
2
Department of Community and Family Medicine; Section of Biostatistics and Epidemiology; Geisel School of Medicine at Dartmouth; Hanover, NH USA.
3
Department of Genetics; Geisel School of Medicine at Dartmouth; Hanover, NH USA.

Abstract

Age is a key risk factor for breast cancer and epigenetic alterations may contribute to age-related increases in breast cancer risk, though the relation of age-related methylation in normal breast tissues with altered methylation in breast tumors is unclear. We investigated the relation of age with DNA methylation in normal breast tissues genome-wide using two data sets from the Gene Expression Omnibus (GEO) database (GSE32393 and GSE31979). We validated our observations in an independent set of normal breast tissues, examined age-related methylation in normal breast for enrichment of genomic features, and compared age-related methylation in normal tissue with methylation alterations in breast tumors. Between the two array-based methylation data sets, there were 204 CpG loci with significant (P<0.05) and consistent age-related methylation, 97% of which were increases in methylation. Our validation sets confirmed the direction of age-related DNA methylation changes in all measured regions. Among the 204 age-related CpG loci, we observed a significant enrichment for CpG islands (P = 8.7E-6) and polycomb group protein target genes (P = 0.03). In addition, 24 of the 204 CpGs with age-related methylation in normal breast were significantly differentially methylated between normal and breast tumor tissues. We identified consistent age-related methylation changes in normal breast tissue that are further altered in breast tumors and may represent early events contributing to breast carcinogenesis. This work identifies age-related methylation in normal breast tissue and begins to deconstruct the contribution of aging to epigenetic alterations present in breast tumors.

KEYWORDS:

Breast; aging; array; cancer; methylation; normal

PMID:
24196486
PMCID:
PMC3962537
DOI:
10.4161/epi.27015
[Indexed for MEDLINE]
Free PMC Article

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