Racial Differences in Healthy Breast Tissues: genome-wide methylation profiling and gene expression in healthy women
Racial differences in DNA methylation have been shown in breast cancers, but it remains unclear if these differences are present among healthy women. The study of normal tissues is distinguished from breast tumor study because it provides understanding of epigenetic predisposition that influences racial disparities in breast cancers.
We performed for the first time comprehensive examination for genome-wide differential DNA methylation and gene expression for European-Americans and African-Americans in histologically-confirmed normal breast tissues from cancer-free women. 485 CpGs were identified to be differentially methylated (DM) between European-Americans and African-Americans. Promoter-related hypermethylated DM CpGs occurred about twice as frequently among European-Americans relative to African-Americans (52% vs. 27%), while the DM CpGs for African-Americans are more likely to be in gene bodies (39%) or intergenic regions (31%). 10% of the DM CpGs (24 in European-Americans and 26 in African-Americans) was significantly correlated with gene expression, and the genes are different. Biological networks of the correlated genes showed different top networks with different genes involved for European-Americans and African-Americans, but both networks were connected through Ubiquitin C. For the 23 most significant relevant DM CpGs (Bonferroni correction), about 26% of them are studied in cancer including breast, which include one oncogene (TNK2) and 4 tumor suppressor genes (AHRR, OPCML, PACS2, and HIPK2).
Our findings show that racial differences in DNA methylation exist among healthy women and that those methylation differences are correlated with gene expression at some levels. We believe that the findings of racial differences in genome-wide DNA methylation within normal breast tissues, coupled with gene expression provide insights into differential early breast cancer mechanisms and carcinogenesis for African-Americans and European-Americans.
Song MA, Brasky TM, Marian C, Weng D, Taslim C, Dumitrescu RG, Llanos AA, Freudenheim JL, & Shields PG (2015). Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women. Epigenetics PMID: 26680018