Genome-wide methylation patterns provide insight into differences in breast tumor biology between American women of African and European ancestry
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Christine B. Ambrosone1, Allyson C. Young2, Lara E. Sucheston1, Dan Wang3, Li Yan3, Song Liu3, Li Tang1, Qiang Hu3, Jo L. Freudenheim4, Peter G. Shields5, Carl D. Morrison6, Kitaw Demissie7, Michael J. Higgins2
1 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY
2 Department of Molecular and Cell Biology, Roswell Park Cancer Institute, Buffalo, NY
3 Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY
4 Department of Social and Preventive Medicine, University at Buffalo, Buffalo, NY
5 College of Medicine, Ohio State University Comprehensive Cancer Center, Columbus, OH
6 Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY
7 Department of Epidemiology, Rutgers School of Public Health and Cancer Institute of New Jersey, NJ
Christine B. Ambrosone, email:
Keywords: DNA methylation; breast cancer; disparities; estrogen receptor; African-American ;genome-wide
Received: November 12, 2013 Accepted: November 28, 2013 Published: November 29, 2013
American women of African ancestry (AA) are more likely than European-Americans (EA) to be diagnosed with aggressive, estrogen receptor (ER) negative breast tumors; mechanisms underlying these disparities are poorly understood. We conducted a genome wide (450K loci) methylation analysis to determine if there were differences in DNA methylation patterns between tumors from AA and EA women and if these differences were similar for both ER positive and ER negative breast cancer. Methylation levels at CpG loci within CpG islands (CGI)s and CGI-shores were significantly higher in tumors (n=138) than in reduction mammoplasty samples (n=124). In hierarchical cluster analysis, there was separation between tumor and normal samples, and in tumors, there was delineation by ER status, but not by ancestry. However, differential methylation analysis identified 157 CpG loci with a mean β value difference of at least 0.17 between races, with almost twice as many differences in ER-negative tumors compared to ER-positive cancers. This first genome-wide methylation study to address disparities indicates that there are likely differing etiologic pathways for the development of ER negative breast cancer between AA and EA women. Further investigation of the genes most differentially methylated by race in ER negative tumors can guide new approaches for cancer prevention and targeted therapies, and elucidate the biologic basis of breast cancer disparities.
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