Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age
Kevin C. Johnson, E. Andres Houseman, Jessica E. King, and Brock C. Christensen
Breast Cancer Research publication link: http://rdcu.be/t5r3
Pre-print link:http://www.biorxiv.org/content/early/2017/01/19/101287
Motivated by our findings in an earlier paper (PMID: 24196486), we set out to test the relation between DNA methylation and breast cancer risk factors in a larger cohort of non-diseased breast tissue. Using histologically normal breast tissues samples from healthy donors (Komen Tissue Bank), we profiled genome-wide methylation levels using the Illumina HumanMethylation450 microarray and carried out a reference-free cell-type adjusted Epigenome-Wide Association Study for several breast cancer risk factors.
We validated our discovery findings from the Komen population using a separate smaller population of non-diseased breast tissue (National Disease Research Interchange) and adjacent-to-tumor normal tissue. We then extended these analyses to investigate how these DNA methylation differences associated with risk factors were further disrupted in both pre-invasive and invasive breast cancer.
100 normal breast tissues (GSE88883, Komen Tissue Bank)
18 normal breast tissues (GSE74214, National Disease Research Interchange)
See 'Komen-Analysis.xlsx' for outline of analyses
For questions about the manuscript or data generation please e-mail: kevin.c.johnson[at]jax.org